CELLULAR, BIOCHEMICAL, AND MOLECULAR TECHNIQUES IN DEVELOPMENTAL TOXICOLOGY

EPA Science Inventory

Cellular, molecular and biochemical approaches vastly expand the possibilities for revealing the underlying mechanisms of developmental toxicity. The increasing interest in embryonic development as a model system for the study of gene expression has resulted in a cornucopia of i...

76 FR 2399 - Center for Scientific Review; Notice of Closed Meetings

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2011-01-13

...: Molecular, Cellular and Developmental Neuroscience Integrated Review Group, Neurotransporters, Receptors...- 1198. [email protected] . Name of Committee: Genes, Genomes, and Genetics Integrated Review Group.... (301) 435-1045. [email protected] . Name of Committee: Molecular, Cellular and Developmental...

75 FR 994 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-07

..., Genomes, and Genetics Integrated Review Group; Molecular Genetics C Study Section. Date: February 4-5...: Molecular, Cellular and Developmental Neuroscience Integrated Review Group; Neural Oxidative Metabolism [email protected] . Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review...

Multi-scale volumetric cell and tissue imaging based on optical projection tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Ban, Sungbea; Cho, Nam Hyun; Ryu, Yongjae; Jung, Sunwoo; Vavilin, Andrey; Min, Eunjung; Jung, Woonggyu

2016-04-01

Optical projection tomography is a new optical imaging method for visualizing small biological specimens in three dimension. The most important advantage of OPT is to fill the gap between MRI and confocal microscope for the specimen having the range of 1-10 mm. Thus, it has been mainly used for whole-mount small animals and developmental study since this imaging modality was developed. The ability of OPT delivering anatomical and functional information of relatively large tissue in 3D has made it a promising platform in biomedical research. Recently, the potential of OPT spans its coverage to cellular scale. Even though there are increasing demand to obtain better understanding of cellular dynamics, only few studies to visualize cellular structure, shape, size and functional morphology over tissue has been investigated in existing OPT system due to its limited field of view. In this study, we develop a novel optical imaging system for 3D cellular imaging with OPT integrated with dynamic focusing technique. Our tomographic setup has great potential to be used for identifying cell characteristic in tissue because it can provide selective contrast on dynamic focal plane allowing for fluorescence as well as absorption. While the dominant contrast of optical imaging technique is to use the fluorescence for detecting certain target only, the newly developed OPT system will offer considerable advantages over currently available method when imaging cellar molecular dynamics by permitting contrast variation. By achieving multi-contrast, it is expected for this new imaging system to play an important role in delivering better cytological information to pathologist.

75 FR 26970 - Center for Scientific Review; Notice of Closed Meetings

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2010-05-13

...-496-8551, [email protected] . Name of Committee: Molecular, Cellular and Developmental...: Oncology 1--Basic Translational Integrated Review Group, Cancer Genetics Study Section. Date: June 3-4... 20892, (301) 435-1154, [email protected] . Name of Committee: Molecular, Cellular and Developmental...

Designing a mathematical model for integrating dynamic cellular manufacturing into supply chain system

NASA Astrophysics Data System (ADS)

Aalaei, Amin; Davoudpour, Hamid

2012-11-01

This article presents designing a new mathematical model for integrating dynamic cellular manufacturing into supply chain system with an extensive coverage of important manufacturing features consideration of multiple plants location, multi-markets allocation, multi-period planning horizons with demand and part mix variation, machine capacity, and the main constraints are demand of markets satisfaction in each period, machine availability, machine time-capacity, worker assignment, available time of worker, production volume for each plant and the amounts allocated to each market. The aim of the proposed model is to minimize holding and outsourcing costs, inter-cell material handling cost, external transportation cost, procurement & maintenance and overhead cost of machines, setup cost, reconfiguration cost of machines installation and removal, hiring, firing and salary worker costs. Aimed to prove the potential benefits of such a design, presented an example is shown using a proposed model.

Fatigue design of a cellular phone folder using regression model-based multi-objective optimization

NASA Astrophysics Data System (ADS)

Kim, Young Gyun; Lee, Jongsoo

2016-08-01

In a folding cellular phone, the folding device is repeatedly opened and closed by the user, which eventually results in fatigue damage, particularly to the front of the folder. Hence, it is important to improve the safety and endurance of the folder while also reducing its weight. This article presents an optimal design for the folder front that maximizes its fatigue endurance while minimizing its thickness. Design data for analysis and optimization were obtained experimentally using a test jig. Multi-objective optimization was carried out using a nonlinear regression model. Three regression methods were employed: back-propagation neural networks, logistic regression and support vector machines. The AdaBoost ensemble technique was also used to improve the approximation. Two-objective Pareto-optimal solutions were identified using the non-dominated sorting genetic algorithm (NSGA-II). Finally, a numerically optimized solution was validated against experimental product data, in terms of both fatigue endurance and thickness index.

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.

QUANTITATIVE IN VITRO MEASUREMENT OF CELLULAR PROCESSES CRITICAL TO THE DEVELOPMENT OF NEURAL CONNECTIVITY USING HCA.

EPA Science Inventory

New methods are needed to screen thousands of environmental chemicals for toxicity, including developmental neurotoxicity. In vitro, cell-based assays that model key cellular events have been proposed for high throughput screening of chemicals for developmental neurotoxicity. Whi...

Load Distribution Factors for Composite Multicell Box Girder Bridges

NASA Astrophysics Data System (ADS)

Tiwari, Sanjay; Bhargava, Pradeep

2017-12-01

Cellular steel section composite with a concrete deck is one of the most suitable superstructures in resisting torsional and warping effects induced by highway loading. This type of structure has inherently created new design problems for engineers in estimating its load distribution when subjected to moving vehicles. Indian Codes of Practice does not provide any specific guidelines for the design of straight composite concrete deck-steel multi-cell bridges. To meet the practical requirements arising during the design process, a simple design method is needed for straight composite multi-cell bridges in the form of load distribution factors for moment and shear. This work presents load distribution characteristics of straight composite multi-cell box girder bridges under IRC trains of loads.

78 FR 57169 - Center for Scientific Review; Notice of Closed Meetings

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2013-09-17

..., Molecular and Integrative Reproduction Study Section. Date: October 9, 2013. Time: 8:00 a.m. to 5:00 p.m...: Molecular, Cellular and Developmental Neuroscience Integrated Review Group; Neurogenesis and Cell Fate [email protected] . Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review...

Designing multi-targeted agents: An emerging anticancer drug discovery paradigm.

PubMed

Fu, Rong-Geng; Sun, Yuan; Sheng, Wen-Bing; Liao, Duan-Fang

2017-08-18

The dominant paradigm in drug discovery is to design ligands with maximum selectivity to act on individual drug targets. With the target-based approach, many new chemical entities have been discovered, developed, and further approved as drugs. However, there are a large number of complex diseases such as cancer that cannot be effectively treated or cured only with one medicine to modulate the biological function of a single target. As simultaneous intervention of two (or multiple) cancer progression relevant targets has shown improved therapeutic efficacy, the innovation of multi-targeted drugs has become a promising and prevailing research topic and numerous multi-targeted anticancer agents are currently at various developmental stages. However, most multi-pharmacophore scaffolds are usually discovered by serendipity or screening, while rational design by combining existing pharmacophore scaffolds remains an enormous challenge. In this review, four types of multi-pharmacophore modes are discussed, and the examples from literature will be used to introduce attractive lead compounds with the capability of simultaneously interfering with different enzyme or signaling pathway of cancer progression, which will reveal the trends and insights to help the design of the next generation multi-targeted anticancer agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Reverse engineering development: Crosstalk opportunities between developmental biology and tissue engineering.

PubMed

Marcucio, Ralph S; Qin, Ling; Alsberg, Eben; Boerckel, Joel D

2017-11-01

The fields of developmental biology and tissue engineering have been revolutionized in recent years by technological advancements, expanded understanding, and biomaterials design, leading to the emerging paradigm of "developmental" or "biomimetic" tissue engineering. While developmental biology and tissue engineering have long overlapping histories, the fields have largely diverged in recent years at the same time that crosstalk opportunities for mutual benefit are more salient than ever. In this perspective article, we will use musculoskeletal development and tissue engineering as a platform on which to discuss these emerging crosstalk opportunities and will present our opinions on the bright future of these overlapping spheres of influence. The multicellular programs that control musculoskeletal development are rapidly becoming clarified, represented by shifting paradigms in our understanding of cellular function, identity, and lineage specification during development. Simultaneously, advancements in bioartificial matrices that replicate the biochemical, microstructural, and mechanical properties of developing tissues present new tools and approaches for recapitulating development in tissue engineering. Here, we introduce concepts and experimental approaches in musculoskeletal developmental biology and biomaterials design and discuss applications in tissue engineering as well as opportunities for tissue engineering approaches to inform our understanding of fundamental biology. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2356-2368, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Design of a dynamic test platform for autonomous robot vision systems

NASA Technical Reports Server (NTRS)

Rich, G. C.

1980-01-01

The concept and design of a dynamic test platform for development and evluation of a robot vision system is discussed. The platform is to serve as a diagnostic and developmental tool for future work with the RPI Mars Rover's multi laser/multi detector vision system. The platform allows testing of the vision system while its attitude is varied, statically or periodically. The vision system is mounted on the test platform. It can then be subjected to a wide variety of simulated can thus be examined in a controlled, quantitative fashion. Defining and modeling Rover motions and designing the platform to emulate these motions are also discussed. Individual aspects of the design process are treated separately, as structural, driving linkages, and motors and transmissions.

Fluorescence multi-scale endoscopy and its applications in the study and diagnosis of gastro-intestinal diseases: set-up design and software implementation

NASA Astrophysics Data System (ADS)

Gómez-García, Pablo Aurelio; Arranz, Alicia; Fresno, Manuel; Desco, Manuel; Mahmood, Umar; Vaquero, Juan José; Ripoll, Jorge

2015-06-01

Endoscopy is frequently used in the diagnosis of several gastro-intestinal pathologies as Crohn disease, ulcerative colitis or colorectal cancer. It has great potential as a non-invasive screening technique capable of detecting suspicious alterations in the intestinal mucosa, such as inflammatory processes. However, these early lesions usually cannot be detected with conventional endoscopes, due to lack of cellular detail and the absence of specific markers. Due to this lack of specificity, the development of new endoscopy technologies, which are able to show microscopic changes in the mucosa structure, are necessary. We here present a confocal endomicroscope, which in combination with a wide field fluorescence endoscope offers fast and specific macroscopic information through the use of activatable probes and a detailed analysis at cellular level of the possible altered tissue areas. This multi-modal and multi-scale imaging module, compatible with commercial endoscopes, combines near-infrared fluorescence (NIRF) measurements (enabling specific imaging of markers of disease and prognosis) and confocal endomicroscopy making use of a fiber bundle, providing a cellular level resolution. The system will be used in animal models exhibiting gastro-intestinal diseases in order to analyze the use of potential diagnostic markers in colorectal cancer. In this work, we present in detail the set-up design and the software implementation in order to obtain simultaneous RGB/NIRF measurements and short confocal scanning times.

Assessing Cardiovascular Responses to Stressors in Individuals with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Groden, June; Goodwin, Matthew S.; Baron, M. Grace; Groden, Gerald; Velicer, Wayne F.; Lipsitt, Lewis P.; Hofmann, Stefan G.; Plummer, Brett

2005-01-01

Characteristics of persons with autism and other developmental disabilities may make this population especially vulnerable to the effects of stress. Prior research on stress and its measurement in this population is reviewed. Using a single-case multi-element design, this study explores the feasibility of measuring cardiovascular responses to four…

Using Research-Based Instruction to Improve Math Outcomes with Underprepared Students

ERIC Educational Resources Information Center

Pearce, Lee R.; Pearce, Kristi L.; Siewert, Daluss J.

2017-01-01

The authors used a mixed-methods research design to evaluate a multi-tiered system of supports model to address the disturbing failure rates of underprepared college students placed in developmental mathematics at a small state university. While qualitative data gathered from using Participatory Action Research methods directed the two-year…

An enhanced high-speed multi-digit BCD adder using quantum-dot cellular automata

NASA Astrophysics Data System (ADS)

Ajitha, D.; Ramanaiah, K. V.; Sumalatha, V.

2017-02-01

The advent of development of high-performance, low-power digital circuits is achieved by a suitable emerging nanodevice called quantum-dot cellular automata (QCA). Even though many efficient arithmetic circuits were designed using QCA, there is still a challenge to implement high-speed circuits in an optimized manner. Among these circuits, one of the essential structures is a parallel multi-digit decimal adder unit with significant speed which is very attractive for future environments. To achieve high speed, a new correction logic formulation method is proposed for single and multi-digit BCD adder. The proposed enhanced single-digit BCD adder (ESDBA) is 26% faster than the carry flow adder (CFA)-based BCD adder. The multi-digit operations are also performed using the proposed ESDBA, which is cascaded innovatively. The enhanced multi-digit BCD adder (EMDBA) performs two 4-digit and two 8-digit BCD addition 50% faster than the CFA-based BCD adder with the nominal overhead of the area. The EMDBA performs two 4-digit BCD addition 24% faster with 23% decrease in the area, similarly for 8-digit operation the EMDBA achieves 36% increase in speed with 21% less area compared to the existing carry look ahead (CLA)-based BCD adder design. The proposed multi-digit adder produces significantly less delay of (N –1) + 3.5 clock cycles compared to the N* One digit BCD adder delay required by the conventional BCD adder method. It is observed that as per our knowledge this is the first innovative proposal for multi-digit BCD addition using QCA.

Virtual Embryo: Cell-Agent Based Modeling of Developmental Processes and Toxicities (CSS BOSC)

EPA Science Inventory

Spatial regulation of cellular dynamics is fundamental to morphological development. As such, chemical disruption of spatial dynamics is a determinant of developmental toxicity. Incorporating spatial dynamics into AOPs for developmental toxicity is desired but constrained by the ...

Can multi-generational exposure to ocean warming and acidification lead to the adaptation of life history and physiology in a marine metazoan?

PubMed

Gibbin, Emma M; Chakravarti, Leela J; Jarrold, Michael D; Christen, Felix; Turpin, Vincent; Massamba N'Siala, Gloria; Blier, Pierre U; Calosi, Piero

2017-02-15

Ocean warming and acidification are concomitant global drivers that are currently threatening the survival of marine organisms. How species will respond to these changes depends on their capacity for plastic and adaptive responses. Little is known about the mechanisms that govern plasticity and adaptability or how global changes will influence these relationships across multiple generations. Here, we exposed the emerging model marine polychaete Ophryotrocha labronica to conditions simulating ocean warming and acidification, in isolation and in combination over five generations to identify: (i) how multiple versus single global change drivers alter both juvenile and adult life-history traits; (ii) the mechanistic link between adult physiological and fitness-related life-history traits; and (iii) whether the phenotypic changes observed over multiple generations are of plastic and/or adaptive origin. Two juvenile (developmental rate; survival to sexual maturity) and two adult (average reproductive body size; fecundity) life-history traits were measured in each generation, in addition to three physiological (cellular reactive oxygen species content, mitochondrial density, mitochondrial capacity) traits. We found that multi-generational exposure to warming alone caused an increase in juvenile developmental rate, reactive oxygen species production and mitochondrial density, decreases in average reproductive body size and fecundity, and fluctuations in mitochondrial capacity, relative to control conditions. Exposure to ocean acidification alone had only minor effects on juvenile developmental rate. Remarkably, when both drivers of global change were present, only mitochondrial capacity was significantly affected, suggesting that ocean warming and acidification act as opposing vectors of stress across multiple generations. © 2017. Published by The Company of Biologists Ltd.

Programming self-organizing multicellular structures with synthetic cell-cell signaling.

PubMed

Toda, Satoshi; Blauch, Lucas R; Tang, Sindy K Y; Morsut, Leonardo; Lim, Wendell A

2018-05-31

A common theme in the self-organization of multicellular tissues is the use of cell-cell signaling networks to induce morphological changes. We used the modular synNotch juxtacrine signaling platform to engineer artificial genetic programs in which specific cell-cell contacts induced changes in cadherin cell adhesion. Despite their simplicity, these minimal intercellular programs were sufficient to yield assemblies with hallmarks of natural developmental systems: robust self-organization into multi-domain structures, well-choreographed sequential assembly, cell type divergence, symmetry breaking, and the capacity for regeneration upon injury. The ability of these networks to drive complex structure formation illustrates the power of interlinking cell signaling with cell sorting: signal-induced spatial reorganization alters the local signals received by each cell, resulting in iterative cycles of cell fate branching. These results provide insights into the evolution of multi-cellularity and demonstrate the potential to engineer customized self-organizing tissues or materials. Copyright © 2018, American Association for the Advancement of Science.

A Multi-Media CAI Terminal Based upon a Microprocessor with Applications for the Handicapped.

ERIC Educational Resources Information Center

Brebner, Ann; Hallworth, H. J.

The design of the CAI interface described is based on the microprocessor in order to meet three basic requirements for providing appropriate instruction to the developmentally handicapped: (1) portability, so that CAI can be taken into the customary learning environment; (2) reliability; and (3) flexibility, to permit use of new input and output…

An Evaluation of Multi-Component Exposure Treatment of Needle Phobia in an Adult with Autism and Intellectual Disability

ERIC Educational Resources Information Center

Wolff, Jason J.; Symons, Frank J.

2013-01-01

Background: Fear of medical procedures in general and needles in particular can be a difficult clinical challenge to providing effective health care for individuals with intellectual and developmental disabilities. Methods: A changing criterion design was used to examine graduated exposure treatment for blood-injury-injection phobia in an adult…

A Cognitively-Based Communication Curriculum for Persons with Multiple Handicaps Functioning between 0-24 Months Developmentally.

ERIC Educational Resources Information Center

McMullen, Victoria B.

This curriculum provides a sequence of activities designed to help develop cognitive and communication skills in severely and profoundly multi-handicapped individuals who are functioning between 0 and 24 months. Based on the principles that communication begins at birth and that educational programming must begin at the point where the handicapped…

Reserch on Urban Spatial Expansion Model Based on Multi-Object Gray Decision-Making and Ca: a Case Study of Pidu District, Chengdu City

NASA Astrophysics Data System (ADS)

Liu, Z.; Li, Y.

2018-04-01

This paper from the perspective of the Neighbor cellular space, Proposed a new urban space expansion model based on a new multi-objective gray decision and CA. The model solved the traditional cellular automata conversion rules is difficult to meet the needs of the inner space-time analysis of urban changes and to overcome the problem of uncertainty in the combination of urban drivers and urban cellular automata. At the same time, the study takes Pidu District as a research area and carries out urban spatial simulation prediction and analysis, and draws the following conclusions: (1) The design idea of the urban spatial expansion model proposed in this paper is that the urban driving factor and the neighborhood function are tightly coupled by the multi-objective grey decision method based on geographical conditions. The simulation results show that the simulation error of urban spatial expansion is less than 5.27 %. The Kappa coefficient is 0.84. It shows that the model can better capture the inner transformation mechanism of the city. (2) We made a simulation prediction for Pidu District of Chengdu by discussing Pidu District of Chengdu as a system instance.In this way, we analyzed the urban growth tendency of this area.presenting a contiguous increasing mode, which is called "urban intensive development". This expansion mode accorded with sustainable development theory and the ecological urbanization design theory.

Rewiring of the inferred protein interactome during blood development studied with the tool PPICompare.

PubMed

Will, Thorsten; Helms, Volkhard

2017-04-04

Differential analysis of cellular conditions is a key approach towards understanding the consequences and driving causes behind biological processes such as developmental transitions or diseases. The progress of whole-genome expression profiling enabled to conveniently capture the state of a cell's transcriptome and to detect the characteristic features that distinguish cells in specific conditions. In contrast, mapping the physical protein interactome for many samples is experimentally infeasible at the moment. For the understanding of the whole system, however, it is equally important how the interactions of proteins are rewired between cellular states. To overcome this deficiency, we recently showed how condition-specific protein interaction networks that even consider alternative splicing can be inferred from transcript expression data. Here, we present the differential network analysis tool PPICompare that was specifically designed for isoform-sensitive protein interaction networks. Besides detecting significant rewiring events between the interactomes of grouped samples, PPICompare infers which alterations to the transcriptome caused each rewiring event and what is the minimal set of alterations necessary to explain all between-group changes. When applied to the development of blood cells, we verified that a reasonable amount of rewiring events were reported by the tool and found that differential gene expression was the major determinant of cellular adjustments to the interactome. Alternative splicing events were consistently necessary in each developmental step to explain all significant alterations and were especially important for rewiring in the context of transcriptional control. Applying PPICompare enabled us to investigate the dynamics of the human protein interactome during developmental transitions. A platform-independent implementation of the tool PPICompare is available at https://sourceforge.net/projects/ppicompare/ .

The Armys Armored Multi Purpose Vehicle (AMPV): Background and Issues for Congress

DTIC Science & Technology

2016-02-24

vehicles and provide protection against the challenging threats that the ABCTs are designed to fight against (page 2).  Because the medical evacuation ...carriers, and medical treatment and evacuation vehicles. An estimated 3,000 of these M-113 variants are currently in service with the Army. The AMPV is...not vehicles that are specially designed and not currently in service). Some suggest that a non-developmental vehicle might make it easier for the

Meeting report of the 2016 bone marrow adiposity meeting.

PubMed

van der Eerden, Bram; van Wijnen, André

2017-10-02

There is considerable interest in the physiology and pathology, as well as the cellular and molecular biology, of bone marrow adipose tissue (BMAT). Because bone marrow adiposity is linked not only to systemic energy metabolism, but also to both bone marrow and musculoskeletal disorders, this biologic compartment has become of major interest to investigators from diverse disciplines. Bone marrow adiposity represents a virtual multi-tissue endocrine organ, which encompasses cells from multiple developmental lineages (e.g., mesenchymal, myeloid, lymphoid) and occupies all the non-osseous and non-cartilaginous space within long bones. A number of research groups are now focusing on bone marrow adiposity to understand a range of clinical afflictions associated with bone marrow disorders and to consider mechanisms-based strategies for future therapies.

Expression of endogenous proteins in maize hybrids in a multi-location field trial in India.

PubMed

Gutha, Linga R; Purushottam, Divakar; Veeramachaneni, Aruna; Tigulla, Sarita; Kodappully, Vikas; Enjala, Chandana; Rajput, Hitendrasinh; Anderson, Jennifer; Hong, Bonnie; Schmidt, Jean; Bagga, Shveta

2018-05-17

Genetically modified (GM) crops undergo large scale multi-location field trials to characterize agronomics, composition, and the concentration of newly expressed protein(s) [herein referred to as transgenic protein(s)]. The concentration of transgenic proteins in different plant tissues and across the developmental stages of the plant is considered in the safety assessment of GM crops. Reference or housekeeping proteins are expected to maintain a relatively stable expression pattern in healthy plants given their role in cellular functions. Understanding the effects of genotype, growth stage and location on the concentration of endogenous housekeeping proteins may provide insight into the contribution these factors could have on transgenic protein concentrations in GM crops. The concentrations of three endogenous proteins (actin, elongation factor 1-alpha, and glyceraldehyde 3-phosphate dehydrogenase) were measured in several different maize hybrids grown across multiple field locations over 2 years. Leaf samples were collected from healthy plants at three developmental stages across the growing seasons, and protein concentrations were quantified by indirect enzyme-linked immunosorbent assay (ELISA) for each protein. In general, the concentrations of these three endogenous proteins were relatively consistent across hybrid backgrounds, when compared within one growth stage and location (2-26%CV), whereas the concentrations of proteins in the same hybrid and growth stage across different locations were more variable (12-64%CV). In general, the protein concentrations in 2013 and 2014 show similar trends in variability. Some degree of variability in protein concentrations should be expected for both transgenic and endogenous plant-expressed proteins. In the case of GM crops, the potential variation in protein concentrations due to location effects is captured in the current model of multi-location field testing.

A tribute to Dr. Gordon Hisashi Sato (December 24, 1927-March 31, 2017).

PubMed

Sato, J Denry; Okamoto, Tetsuji; Barnes, David; Hayashi, Jun; Serrero, Ginette; McKeehan, Wallace L

2018-03-01

Gordon H. Sato, an innovator in mammalian tissue culture and integrated cellular physiology, passed away in 2017. In tribute to Dr. Sato, In Vitro Cellular and Developmental Biology-Animal presents a collection of invited remembrances from six colleagues whose associations with Dr. Sato spanned more than 40 years. Dr. Sato was a past president of the Tissue Culture Association (now the Society for In Vitro Biology), editor-in-chief of In Vitro Cellular and Developmental Biology (1987-1991), and the recipient of the lifetime achievement award from the Society for In Vitro Biology (2002). He was elected to the US National Academy of Sciences in 1984.

Building quantitative, three-dimensional atlases of gene expression and morphology at cellular resolution.

PubMed

Knowles, David W; Biggin, Mark D

2013-01-01

Animals comprise dynamic three-dimensional arrays of cells that express gene products in intricate spatial and temporal patterns that determine cellular differentiation and morphogenesis. A rigorous understanding of these developmental processes requires automated methods that quantitatively record and analyze complex morphologies and their associated patterns of gene expression at cellular resolution. Here we summarize light microscopy-based approaches to establish permanent, quantitative datasets-atlases-that record this information. We focus on experiments that capture data for whole embryos or large areas of tissue in three dimensions, often at multiple time points. We compare and contrast the advantages and limitations of different methods and highlight some of the discoveries made. We emphasize the need for interdisciplinary collaborations and integrated experimental pipelines that link sample preparation, image acquisition, image analysis, database design, visualization, and quantitative analysis. Copyright © 2013 Wiley Periodicals, Inc.

Ciona intestinalis notochord as a new model to investigate the cellular and molecular mechanisms of tubulogenesis.

PubMed

Denker, Elsa; Jiang, Di

2012-05-01

Biological tubes are a prevalent structural design across living organisms. They provide essential functions during the development and adult life of an organism. Increasing progress has been made recently in delineating the cellular and molecular mechanisms underlying tubulogenesis. This review aims to introduce ascidian notochord morphogenesis as an interesting model system to study the cell biology of tube formation, to a wider cell and developmental biology community. We present fundamental morphological and cellular events involved in notochord morphogenesis, compare and contrast them with other more established tubulogenesis model systems, and point out some unique features, including bipolarity of the notochord cells, and using cell shape changes and cell rearrangement to connect lumens. We highlight some initial findings in the molecular mechanisms of notochord morphogenesis. Based on these findings, we present intriguing problems and put forth hypotheses that can be addressed in future studies. Copyright © 2012 Elsevier Ltd. All rights reserved.

MULTI-STAGE DELIVERY NANO-PARTICLE SYSTEMS FOR THERAPEUTIC APPLICATIONS

PubMed Central

Serda, Rita E.; Godin, Biana; Blanco, Elvin; Chiappini, Ciro; Ferrari, Mauro

2010-01-01

Background The daunting task for drug molecules to reach pathological lesions has fueled rapid advances in Nanomedicine. The progressive evolution of nanovectors has led to the development of multi-stage delivery systems aimed at overcoming the numerous obstacles encountered by nanovectors on their journey to the target site. Scope of Review This review summarizes major findings with respect to silicon-based drug delivery vectors for cancer therapeutics and imaging. Based on rational design, well established silicon technologies have been adapted for the fabrication of nanovectors with specific shapes, sizes, and porosities. These vectors are part of a multi-stage delivery system that contains multiple nano-components, each designed to achieve a specific task with the common goal of site-directed delivery of therapeutics. Major Conclusions Quasi-hemispherical and discoidal silicon microparticles are superior to spherical particles with respect to margination in the blood, with particles of different shapes and sizes having unique distributions in vivo. Cellular adhesion and internalization of silicon microparticles is influenced by microparticle shape and surface charge, with the latter dictating binding of serum opsonins. Based on in vitro cell studies, the internalization of porous silicon microparticles by endothelial cells and macrophages is compatible with cellular morphology, intracellular trafficking, mitosis, cell cycle progression, cytokine release, and cell viability. In vivo studies support superior therapeutic efficacy of liposomal encapsulated siRNA when delivered in multi-stage systems compared to free nanoparticles. PMID:20493927

Multi-scale computational modeling of developmental biology.

PubMed

Setty, Yaki

2012-08-01

Normal development of multicellular organisms is regulated by a highly complex process in which a set of precursor cells proliferate, differentiate and move, forming over time a functioning tissue. To handle their complexity, developmental systems can be studied over distinct scales. The dynamics of each scale is determined by the collective activity of entities at the scale below it. I describe a multi-scale computational approach for modeling developmental systems and detail the methodology through a synthetic example of a developmental system that retains key features of real developmental systems. I discuss the simulation of the system as it emerges from cross-scale and intra-scale interactions and describe how an in silico study can be carried out by modifying these interactions in a way that mimics in vivo experiments. I highlight biological features of the results through a comparison with findings in Caenorhabditis elegans germline development and finally discuss about the applications of the approach in real developmental systems and propose future extensions. The source code of the model of the synthetic developmental system can be found in www.wisdom.weizmann.ac.il/~yaki/MultiScaleModel. yaki.setty@gmail.com Supplementary data are available at Bioinformatics online.

From Stochastic Foam to Designed Structure: Balancing Cost and Performance of Cellular Metals

PubMed Central

Lehmhus, Dirk; Vesenjak, Matej

2017-01-01

Over the past two decades, a large number of metallic foams have been developed. In recent years research on this multi-functional material class has further intensified. However, despite their unique properties only a limited number of large-scale applications have emerged. One important reason for this sluggish uptake is their high cost. Many cellular metals require expensive raw materials, complex manufacturing procedures, or a combination thereof. Some attempts have been made to decrease costs by introducing novel foams based on cheaper components and new manufacturing procedures. However, this has often yielded materials with unreliable properties that inhibit utilization of their full potential. The resulting balance between cost and performance of cellular metals is probed in this editorial, which attempts to consider cost not in absolute figures, but in relation to performance. To approach such a distinction, an alternative classification of cellular metals is suggested which centers on structural aspects and the effort of realizing them. The range thus covered extends from fully stochastic foams to cellular structures designed-to-purpose. PMID:28786935

Evaluation of Title I Program, Community School Distrlct 31, New York City. 1978-79 School Year. Final Report, E.D.L. Reading Lab.

ERIC Educational Resources Information Center

Knight, Michael E.

This program was designed to improve reading skills and to provide intensive remediation for students in grades six through nine. Specialized materials and equipment were provided by Educational Development Laboratories (EDL). The EDL Reading Laboratory utilized the Learning 100 program, a multi-modality developmental and remedial program. Small…

Advances in combined endoscopic fluorescence confocal microscopy and optical coherence tomography

NASA Astrophysics Data System (ADS)

Risi, Matthew D.

Confocal microendoscopy provides real-time high resolution cellular level images via a minimally invasive procedure. Results from an ongoing clinical study to detect ovarian cancer with a novel confocal fluorescent microendoscope are presented. As an imaging modality, confocal fluorescence microendoscopy typically requires exogenous fluorophores, has a relatively limited penetration depth (100 μm), and often employs specialized aperture configurations to achieve real-time imaging in vivo. Two primary research directions designed to overcome these limitations and improve diagnostic capability are presented. Ideal confocal imaging performance is obtained with a scanning point illumination and confocal aperture, but this approach is often unsuitable for real-time, in vivo biomedical imaging. By scanning a slit aperture in one direction, image acquisition speeds are greatly increased, but at the cost of a reduction in image quality. The design, implementation, and experimental verification of a custom multi-point-scanning modification to a slit-scanning multi-spectral confocal microendoscope is presented. This new design improves the axial resolution while maintaining real-time imaging rates. In addition, the multi-point aperture geometry greatly reduces the effects of tissue scatter on imaging performance. Optical coherence tomography (OCT) has seen wide acceptance and FDA approval as a technique for ophthalmic retinal imaging, and has been adapted for endoscopic use. As a minimally invasive imaging technique, it provides morphological characteristics of tissues at a cellular level without requiring the use of exogenous fluorophores. OCT is capable of imaging deeper into biological tissue (˜1-2 mm) than confocal fluorescence microscopy. A theoretical analysis of the use of a fiber-bundle in spectral-domain OCT systems is presented. The fiber-bundle enables a flexible endoscopic design and provides fast, parallelized acquisition of the optical coherence tomography data. However, the multi-mode characteristic of the fibers in the fiber-bundle affects the depth sensitivity of the imaging system. A description of light interference in a multi-mode fiber is presented along with numerical simulations and experimental studies to illustrate the theoretical analysis.

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.

77 FR 2738 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-19

..., Review Group; Clinical Molecular Imaging and Probe Development. Date: February 2-3, 2012. Time: 7 p.m. to..., Bethesda, MD 20892, (301) 435-1777, [email protected] . Name of Committee: Molecular, Cellular and...: Molecular, Cellular and Developmental Neuroscience Integrated Review Group; Cellular and Molecular Biology...

77 FR 30021 - Center for Scientific Review Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-21

... personal privacy. Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review Group; Cellular and Molecular Biology of Glia Study Section. Date: June 14, 2012. Time: 8:00 a.m. to 7..., Bethesda, MD 20892, (301) 435- 4433, [email protected] . Name of Committee: Molecular, Cellular and...

Cellular basis of morphological variation and temperature-related plasticity in Drosophila melanogaster strains with divergent wing shapes.

PubMed

Torquato, Libéria Souza; Mattos, Daniel; Matta, Bruna Palma; Bitner-Mathé, Blanche Christine

2014-12-01

Organ shape evolves through cross-generational changes in developmental patterns at cellular and/or tissue levels that ultimately alter tissue dimensions and final adult proportions. Here, we investigated the cellular basis of an artificially selected divergence in the outline shape of Drosophila melanogaster wings, by comparing flies with elongated or rounded wing shapes but with remarkably similar wing sizes. We also tested whether cellular plasticity in response to developmental temperature was altered by such selection. Results show that variation in cellular traits is associated with wing shape differences, and that cell number may play an important role in wing shape response to selection. Regarding the effects of developmental temperature, a size-related plastic response was observed, in that flies reared at 16 °C developed larger wings with larger and more numerous cells across all intervein regions relative to flies reared at 25 °C. Nevertheless, no conclusive indication of altered phenotypic plasticity was found between selection strains for any wing or cellular trait. We also described how cell area is distributed across different intervein regions. It follows that cell area tends to decrease along the anterior wing compartment and increase along the posterior one. Remarkably, such pattern was observed not only in the selected strains but also in the natural baseline population, suggesting that it might be canalized during development and was not altered by the intense program of artificial selection for divergent wing shapes.

Systems Modeling in Developmental Toxicity

EPA Science Inventory

An individual starts off as a single cell, the progeny of which form complex structures that are themselves integrated into progressively larger systems. Developmental biology is concerned with how this cellular complexity and patterning arises through orchestration of cell divi...

77 FR 28886 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-16

..., Functional and Cognitive Neuroscience Integrated Review Group; Sensorimotor Integration Study Section. Date... and Developmental Neuroscience Integrated Review Group; Neural Oxidative Metabolism and Death Study...: Molecular, Cellular and Developmental Neuroscience Integrated Review Group; Neurodifferentiation, Plasticity...

A dynamically reconfigurable logic cell: from artificial neural networks to quantum-dot cellular automata

NASA Astrophysics Data System (ADS)

Naqvi, Syed Rameez; Akram, Tallha; Iqbal, Saba; Haider, Sajjad Ali; Kamran, Muhammad; Muhammad, Nazeer

2018-02-01

Considering the lack of optimization support for Quantum-dot Cellular Automata, we propose a dynamically reconfigurable logic cell capable of implementing various logic operations by means of artificial neural networks. The cell can be reconfigured to any 2-input combinational logic gate by altering the strength of connections, called weights and biases. We demonstrate how these cells may appositely be organized to perform multi-bit arithmetic and logic operations. The proposed work is important in that it gives a standard implementation of an 8-bit arithmetic and logic unit for quantum-dot cellular automata with minimal area and latency overhead. We also compare the proposed design with a few existing arithmetic and logic units, and show that it is more area efficient than any equivalent available in literature. Furthermore, the design is adaptable to 16, 32, and 64 bit architectures.

Genome-wide chromatin state transitions associated with developmental and environmental cues.

PubMed

Zhu, Jiang; Adli, Mazhar; Zou, James Y; Verstappen, Griet; Coyne, Michael; Zhang, Xiaolan; Durham, Timothy; Miri, Mohammad; Deshpande, Vikram; De Jager, Philip L; Bennett, David A; Houmard, Joseph A; Muoio, Deborah M; Onder, Tamer T; Camahort, Ray; Cowan, Chad A; Meissner, Alexander; Epstein, Charles B; Shoresh, Noam; Bernstein, Bradley E

2013-01-31

Differences in chromatin organization are key to the multiplicity of cell states that arise from a single genetic background, yet the landscapes of in vivo tissues remain largely uncharted. Here, we mapped chromatin genome-wide in a large and diverse collection of human tissues and stem cells. The maps yield unprecedented annotations of functional genomic elements and their regulation across developmental stages, lineages, and cellular environments. They also reveal global features of the epigenome, related to nuclear architecture, that also vary across cellular phenotypes. Specifically, developmental specification is accompanied by progressive chromatin restriction as the default state transitions from dynamic remodeling to generalized compaction. Exposure to serum in vitro triggers a distinct transition that involves de novo establishment of domains with features of constitutive heterochromatin. We describe how these global chromatin state transitions relate to chromosome and nuclear architecture, and discuss their implications for lineage fidelity, cellular senescence, and reprogramming. Copyright © 2013 Elsevier Inc. All rights reserved.

The NASA Specialized Center of Research and Training (NSCORT) in Gravitational Biology

NASA Technical Reports Server (NTRS)

Spooner, B. S.; Guikema, J. A.

1992-01-01

The Life Sciences Division of NASA has initiated a NASA Specialized Centers of Research and Training (NSCORT) program. Three Centers were designated in late 1990, as the culmination of an in-depth peer review analysis of proposals from universities across the nation and around the world. Kansas State University was selected as the NSCORT in Gravitational Biology. This Center is headquartered in the KSU Division of Biology and has a research, training, and outreach function that focuses on cellular and developmental biology.

Insects as test systems for assessing the potential role of microgravity in biological development and evolution.

PubMed

Vernós, I; Carratalá, M; González-Jurado, J; Valverde, J R; Calleja, M; Domingo, A; Vinós, J; Cervera, M; Marco, R

1989-01-01

Gravity and radiation are undoubtedly the two major environmental factors altered in space. Gravity is a weak force, which creates a permanent potential field acting on the mass of biological systems and their cellular components, strongly reduced in space flights. Developmental systems, particularly at very early stages, provide the larger cellular compartments known, where the effects of alterations in the size of the gravity vector on living organisms can be more effectively tested. The insects, one of the more highly evolved classes of animals in which early development occurs in a syncytial embryo, are systems particularly well suited to test these effects and the specific developmental mechanisms affected. Furthermore, they share some basic features such as small size, short life cycles, relatively high radio-resistance, etc. and show a diversity of developmental strategies and tempos advantageous in experiments of this type in space. Drosophila melanogaster, the current biological paradigm to study development, with so much genetic and evolutionary background available, is clearly the reference organism for these studies. The current evidence on the effects of the physical parameters altered in space flights on insect development indicate a surprising correlation between effects seen on the fast developing and relatively small Drosophila embryo and the more slowly developing and large Carausius morosus system. In relation to the issue of the importance of developmental and environmental constraints in biological evolution, still the missing link in current evolutionary thinking, insects and space facilities for long-term experiments could provide useful experimental settings where to critically assess how development and evolution may be interconnected. Finally, it has to be pointed out that since there are experimental data indicating a possible synergism between microgravity and space radiation, possible effects of space radiation should be taken into account in the planning and evaluation of experiments designed to test the potential role of microgravity on biological developmental and evolution.

In Vitro Experimental Model for the Long-Term Analysis of Cellular Dynamics During Bronchial Tree Development from Lung Epithelial Cells

PubMed Central

Maruta, Naomichi; Marumoto, Moegi

2017-01-01

Lung branching morphogenesis has been studied for decades, but the underlying developmental mechanisms are still not fully understood. Cellular movements dynamically change during the branching process, but it is difficult to observe long-term cellular dynamics by in vivo or tissue culture experiments. Therefore, developing an in vitro experimental model of bronchial tree would provide an essential tool for developmental biology, pathology, and systems biology. In this study, we succeeded in reconstructing a bronchial tree in vitro by using primary human bronchial epithelial cells. A high concentration gradient of bronchial epithelial cells was required for branching initiation, whereas homogeneously distributed endothelial cells induced the formation of successive branches. Subsequently, the branches grew in size to the order of millimeter. The developed model contains only two types of cells and it facilitates the analysis of lung branching morphogenesis. By taking advantage of our experimental model, we carried out long-term time-lapse observations, which revealed self-assembly, collective migration with leader cells, rotational motion, and spiral motion of epithelial cells in each developmental event. Mathematical simulation was also carried out to analyze the self-assembly process and it revealed simple rules that govern cellular dynamics. Our experimental model has provided many new insights into lung development and it has the potential to accelerate the study of developmental mechanisms, pattern formation, left–right asymmetry, and disease pathogenesis of the human lung. PMID:28471293

A scientific role for Space Station Freedom: Research at the cellular level

NASA Technical Reports Server (NTRS)

Johnson, Terry C.; Brady, John N.

1993-01-01

The scientific importance of Space Station Freedom is discussed in light of the valuable information that can be gained in cellular and developmental biology with regard to the microgravity environment on the cellular cytoskeleton, cellular responses to extracellular signal molecules, morphology, events associated with cell division, and cellular physiology. Examples of studies in basic cell biology, as well as their potential importance to concerns for future enabling strategies, are presented.

Dancing with Swarms: Utilizing Swarm Intelligence to Build, Investigate, and Control Complex Systems

NASA Astrophysics Data System (ADS)

Jacob, Christian

We are surrounded by a natural world of massively parallel, decentralized biological "information processing" systems, a world that exhibits fascinating emergent properties in many ways. In fact, our very own bodies are the result of emergent patterns, as the development of any multi-cellular organism is determined by localized interactions among an enormous number of cells, carefully orchestrated by enzymes, signalling proteins and other molecular "agents". What is particularly striking about these highly distributed developmental processes is that a centralized control agency is completely absent. This is also the case for many other biological systems, such as termites which build their nests—without an architect that draws a plan, or brain cells evolving into a complex `mind machine'—without an explicit blueprint of a network layout.

Meeting report of the 2016 bone marrow adiposity meeting

PubMed Central

van der Eerden, Bram; van Wijnen, André

2017-01-01

Abstract There is considerable interest in the physiology and pathology, as well as the cellular and molecular biology, of bone marrow adipose tissue (BMAT). Because bone marrow adiposity is linked not only to systemic energy metabolism, but also to both bone marrow and musculoskeletal disorders, this biologic compartment has become of major interest to investigators from diverse disciplines. Bone marrow adiposity represents a virtual multi-tissue endocrine organ, which encompasses cells from multiple developmental lineages (e.g., mesenchymal, myeloid, lymphoid) and occupies all the non-osseous and non-cartilaginous space within long bones. A number of research groups are now focusing on bone marrow adiposity to understand a range of clinical afflictions associated with bone marrow disorders and to consider mechanisms-based strategies for future therapies. PMID:28410005

Asynchronous adaptive time step in quantitative cellular automata modeling

PubMed Central

Zhu, Hao; Pang, Peter YH; Sun, Yan; Dhar, Pawan

2004-01-01

Background The behaviors of cells in metazoans are context dependent, thus large-scale multi-cellular modeling is often necessary, for which cellular automata are natural candidates. Two related issues are involved in cellular automata based multi-cellular modeling: how to introduce differential equation based quantitative computing to precisely describe cellular activity, and upon it, how to solve the heavy time consumption issue in simulation. Results Based on a modified, language based cellular automata system we extended that allows ordinary differential equations in models, we introduce a method implementing asynchronous adaptive time step in simulation that can considerably improve efficiency yet without a significant sacrifice of accuracy. An average speedup rate of 4–5 is achieved in the given example. Conclusions Strategies for reducing time consumption in simulation are indispensable for large-scale, quantitative multi-cellular models, because even a small 100 × 100 × 100 tissue slab contains one million cells. Distributed and adaptive time step is a practical solution in cellular automata environment. PMID:15222901

A closed-loop multi-level model of glucose homeostasis

PubMed Central

Uluseker, Cansu; Simoni, Giulia; Dauriz, Marco; Matone, Alice

2018-01-01

Background The pathophysiologic processes underlying the regulation of glucose homeostasis are considerably complex at both cellular and systemic level. A comprehensive and structured specification for the several layers of abstraction of glucose metabolism is often elusive, an issue currently solvable with the hierarchical description provided by multi-level models. In this study we propose a multi-level closed-loop model of whole-body glucose homeostasis, coupled with the molecular specifications of the insulin signaling cascade in adipocytes, under the experimental conditions of normal glucose regulation and type 2 diabetes. Methodology/Principal findings The ordinary differential equations of the model, describing the dynamics of glucose and key regulatory hormones and their reciprocal interactions among gut, liver, muscle and adipose tissue, were designed for being embedded in a modular, hierarchical structure. The closed-loop model structure allowed self-sustained simulations to represent an ideal in silico subject that adjusts its own metabolism to the fasting and feeding states, depending on the hormonal context and invariant to circadian fluctuations. The cellular level of the model provided a seamless dynamic description of the molecular mechanisms downstream the insulin receptor in the adipocytes by accounting for variations in the surrounding metabolic context. Conclusions/Significance The combination of a multi-level and closed-loop modeling approach provided a fair dynamic description of the core determinants of glucose homeostasis at both cellular and systemic scales. This model architecture is intrinsically open to incorporate supplementary layers of specifications describing further individual components influencing glucose metabolism. PMID:29420588

"Peaks, Slumps, and Bumps": Individual Differences in the Development of Creativity in Children and Adolescents.

PubMed

Barbot, Baptiste; Lubart, Todd I; Besançon, Maud

2016-01-01

This article reviews developmental studies of creativity in children and adolescents with a focus on "peaks" and "slumps" that have often been described in the literature. The irregularity of the development of creativity is interpreted in light of conceptual and measurement issues and with regard to the interaction between individual-level resources, task-specific demands, and environmental influences, resulting in apparent individual differences in the development of creativity. The need for longitudinal designs, multidimensional and multi-domain assessment of creative potential limiting the contribution of task-specific factors is outlined and discussed as an important direction for developmental research on creativity. © 2016 Wiley Periodicals, Inc.

Virtual Embryo: Systems Modeling in Developmental Toxicity

EPA Science Inventory

High-throughput screening (HTS) studies are providing a rich source of data that can be applied to chemical profiling to address sensitivity and specificity of molecular targets, biological pathways, cellular and developmental processes. EPA’s ToxCast project is testing 960 uniq...

Real-Time Monitoring of Cellular Bioenergetics with a Multi-Analyte Screen-Printed Electrode

PubMed Central

McKenzie, Jennifer R.; Cognata, Andrew C.; Davis, Anna N.; Wikswo, John P.; Cliffel, David E.

2016-01-01

Real-time monitoring of changes to cellular bioenergetics can provide new insights into mechanisms of action for disease and toxicity. This work describes the development of a multi-analyte screen-printed electrode for the detection of analytes central to cellular bioenergetics: glucose, lactate, oxygen, and pH. Platinum screen-printed electrodes were designed in-house and printed by Pine Research Instrumentation. Electrochemical plating techniques were used to form quasi-reference and pH electrodes. A Dimatix materials inkjet printer was used to deposit enzyme and polymer films to form sensors for glucose, lactate, and oxygen. These sensors were evaluated in bulk solution and microfluidic environments, and found to behave reproducibly and possess a lifetime of up to six weeks. Linear ranges and limits of detection for enzyme-based sensors were found to have an inverse relationship with enzyme loading, and iridium oxide pH sensors were found to have super-Nernstian responses. Preliminary measurements where the sensor was enclosed within a microfluidic channel with RAW 264.7 macrophages were performed to demonstrate the sensors’ capabilities for performing real-time microphysiometry measurements. PMID:26125545

Phenotypic screening for developmental neurotoxicity ...

EPA Pesticide Factsheets

There are large numbers of environmental chemicals with little or no available information on their toxicity, including developmental neurotoxicity. Because of the resource-intensive nature of traditional animal tests, high-throughput (HTP) methods that can rapidly evaluate chemicals for the potential to affect the developing brain are being explored. Typically, HTP screening uses biochemical and molecular assays to detect the interaction of a chemical with a known target or molecular initiating event (e.g., the mechanism of action). For developmental neurotoxicity, however, the mechanism(s) is often unknown. Thus, we have developed assays for detecting chemical effects on the key events of neurodevelopment at the cellular level (e.g., proliferation, differentiation, neurite growth, synaptogenesis, network formation). Cell-based assays provide a test system at a level of biological complexity that encompasses many potential neurotoxic mechanisms. For example, phenotypic assessment of neurite outgrowth at the cellular level can detect chemicals that target kinases, ion channels, or esterases at the molecular level. The results from cell-based assays can be placed in a conceptual framework using an Adverse Outcome Pathway (AOP) which links molecular, cellular, and organ level effects with apical measures of developmental neurotoxicity. Testing a wide range of concentrations allows for the distinction between selective effects on neurodevelopmental and non-specific

Computer-based multisensory learning in children with developmental dyslexia.

PubMed

Kast, Monika; Meyer, Martin; Vögeli, Christian; Gross, Markus; Jäncke, Lutz

2007-01-01

Several attempts have been made to remediate developmental dyslexia using various training environments. Based on the well-known retrieval structure model, the memory strength of phonemes and graphemes should be strengthened by visual and auditory associations between graphemes and phonemes. Using specifically designed training software, we examined whether establishing a multitude of visuo-auditory associations might help to mitigate writing errors in children with developmental dyslexia. Forty-three children with developmental dyslexia and 37 carefully matched normal reading children performed a computer-based writing training (15-20 minutes 4 days a week) for three months with the aim to recode a sequential textual input string into a multi-sensory representation comprising visual and auditory codes (including musical tones). The study included four matched groups: a group of children with developmental dyslexia (n=20) and a control group (n=18) practiced with the training software in the first period (3 months, 15-20 minutes 4 days a week), while a second group of children with developmental dyslexia (n=23) (waiting group) and a second control group (n=19) received no training during the first period. In the second period the children with developmental dyslexia and controls who did not receive training during the first period now took part in the training. Children with developmental dyslexia who did not perform computer-based training during the first period hardly improved their writing skills (post-pre improvement of 0-9%), the dyslexic children receiving training strongly improved their writing skills (post-pre improvement of 19-35%). The group who did the training during the second period also revealed improvement of writing skills (post-pre improvement of 27-35%). Interestingly, we noticed a strong transfer from trained to non-trained words in that the children who underwent the training were also better able to write words correctly that were not part of the training software. In addition, even non-impaired readers and writers (controls) benefited from this training. Three-month of visual-auditory multimedia training strongly improved writing skills in children with developmental dyslexia and non-dyslexic children. Thus, according to the retrieval structure model, multi-sensory training using visual and auditory cues enhances writing performance in children with developmental dyslexia and non-dyslexic children.

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

NASA Astrophysics Data System (ADS)

McCune, Matthew; Kosztin, Ioan

2013-03-01

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

Minimally invasive multimode optical fiber microendoscope for deep brain fluorescence imaging

PubMed Central

Ohayon, Shay; Caravaca-Aguirre, Antonio; Piestun, Rafael; DiCarlo, James J.

2018-01-01

A major open challenge in neuroscience is the ability to measure and perturb neural activity in vivo from well defined neural sub-populations at cellular resolution anywhere in the brain. However, limitations posed by scattering and absorption prohibit non-invasive multi-photon approaches for deep (>2mm) structures, while gradient refractive index (GRIN) endoscopes are relatively thick and can cause significant damage upon insertion. Here, we present a novel micro-endoscope design to image neural activity at arbitrary depths via an ultra-thin multi-mode optical fiber (MMF) probe that has 5–10X thinner diameter than commercially available micro-endoscopes. We demonstrate micron-scale resolution, multi-spectral and volumetric imaging. In contrast to previous approaches, we show that this method has an improved acquisition speed that is sufficient to capture rapid neuronal dynamics in-vivo in rodents expressing a genetically encoded calcium indicator (GCaMP). Our results emphasize the potential of this technology in neuroscience applications and open up possibilities for cellular resolution imaging in previously unreachable brain regions. PMID:29675297

Life cycle thinking and assessment tools on environmentally-benign electronics: Convergent optimization of materials use, end-of-life strategy and environmental policies

NASA Astrophysics Data System (ADS)

Zhou, Xiaoying

The purpose of this study is to integrate the quantitative environmental performance assessment tools and the theory of multi-objective optimization within the boundary of electronic product systems to support the selection among design alternatives in terms of environmental impact, technical criteria, and economic feasibility. To meet with the requirements that result from emerging environmental legislation targeting electronics products, the research addresses an important analytical methodological approach to facilitate environmentally conscious design and end-of-life management with a life cycle viewpoint. A synthesis of diverse assessment tools is applied on a set of case studies: lead-free solder materials selection, cellular phone design, and desktop display technology assessment. In the first part of this work, an in-depth industrial survey of the status and concerns of the U.S. electronics industry on the elimination of lead (Pb) in solders is described. The results show that the trade-offs among environmental consequences, technology challenges, business risks, legislative compliance and stakeholders' preferences must be explicitly, simultaneously, and systematically addressed in the decision-making process used to guide multi-faceted planning of environmental solutions. In the second part of this work, the convergent optimization of the technical cycle, economic cycle and environmental cycle is addressed in a coherent and systematic way using the application of environmentally conscious design of cellular phones. The technical understanding of product structure, components analysis, and materials flow facilitates the development of "Design for Disassembly" guidelines. A bottom-up disassembly analysis on a "bill of materials" based structure at a micro-operational level is utilized to select optimal end-of-life strategies on the basis of economic feasibility. A macro-operational level life cycle model is used to investigate the environmental consequences linking environmental impact with the cellular phone production activities focusing on the upstream manufacturing and end-of-life life cycle stages. The last part of this work, the quantitative elicitation of weighting factors facilitates the comparison of trade-offs in the context of a multi-attribute problem. An integrated analytical approach, Integrated Industrial Ecology Function Deployment (I2-EFD), is proposed to assess alternatives at the design phase of a product system and is validated with the assessment of desktop display technologies and lead-free solder alternatives.

A Multi-Modality CMOS Sensor Array for Cell-Based Assay and Drug Screening.

PubMed

Chi, Taiyun; Park, Jong Seok; Butts, Jessica C; Hookway, Tracy A; Su, Amy; Zhu, Chengjie; Styczynski, Mark P; McDevitt, Todd C; Wang, Hua

2015-12-01

In this paper, we present a fully integrated multi-modality CMOS cellular sensor array with four sensing modalities to characterize different cell physiological responses, including extracellular voltage recording, cellular impedance mapping, optical detection with shadow imaging and bioluminescence sensing, and thermal monitoring. The sensor array consists of nine parallel pixel groups and nine corresponding signal conditioning blocks. Each pixel group comprises one temperature sensor and 16 tri-modality sensor pixels, while each tri-modality sensor pixel can be independently configured for extracellular voltage recording, cellular impedance measurement (voltage excitation/current sensing), and optical detection. This sensor array supports multi-modality cellular sensing at the pixel level, which enables holistic cell characterization and joint-modality physiological monitoring on the same cellular sample with a pixel resolution of 80 μm × 100 μm. Comprehensive biological experiments with different living cell samples demonstrate the functionality and benefit of the proposed multi-modality sensing in cell-based assay and drug screening.

76 FR 27070 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-10

[email protected] . Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review Group; Cellular and Molecular Biology of Neurodegeneration Study Section. Date: June 13-14, 2011. Time... Committee: Population Sciences and Epidemiology Integrated Review Group; Epidemiology of Cancer Study...

Recent advances in prostate development and links to prostatic diseases

PubMed Central

Powers, Ginny L.

2013-01-01

The prostate is a branched ductal-acinar gland that is part of the male reproductive tract. Prostate development depends upon the integration of steroid hormone signals, paracrine interactions between the stromal and epithelial tissue layers, and the actions of cell autonomous factors. Several genes and signalling pathways are known to be required for one or more steps of prostate development including epithelial budding, duct elongation, branching morphogenesis, and/or cellular differentiation. Recent progress in the field of prostate development has included the application of genome-wide technologies including serial analysis of gene expression (SAGE), expression profiling microarrays, and other large scale approaches to identify new genes and pathways that are essential for prostate development. The aggregation of experimental results into online databases by organized multi-lab projects including the Genitourinary Developmental Molecular Atlas Project (GUDMAP) has also accelerated the understanding of molecular pathways that function during prostate development and identified links between prostate anatomy and molecular signaling. Rapid progress has also recently been made in understanding the nature and role of candidate stem cells in the developing and adult prostate. This has included the identification of putative prostate stem cell markers, lineage tracing, and organ reconstitution studies. However, several issues regarding their origin, precise nature, and possible role(s) in disease remain unresolved. Nevertheless, several links between prostatic developmental mechanisms and the pathogenesis of prostatic diseases including benign prostatic hyperplasia and prostate cancer have led to recent progress on targeting developmental pathways as therapeutic strategies for these diseases. PMID:23335485

Developmental Progression in the Coral Acropora digitifera Is Controlled by Differential Expression of Distinct Regulatory Gene Networks

PubMed Central

Reyes-Bermudez, Alejandro; Villar-Briones, Alejandro; Ramirez-Portilla, Catalina; Hidaka, Michio; Mikheyev, Alexander S.

2016-01-01

Corals belong to the most basal class of the Phylum Cnidaria, which is considered the sister group of bilaterian animals, and thus have become an emerging model to study the evolution of developmental mechanisms. Although cell renewal, differentiation, and maintenance of pluripotency are cellular events shared by multicellular animals, the cellular basis of these fundamental biological processes are still poorly understood. To understand how changes in gene expression regulate morphogenetic transitions at the base of the eumetazoa, we performed quantitative RNA-seq analysis during Acropora digitifera’s development. We collected embryonic, larval, and adult samples to characterize stage-specific transcription profiles, as well as broad expression patterns. Transcription profiles reconstructed development revealing two main expression clusters. The first cluster grouped blastula and gastrula and the second grouped subsequent developmental time points. Consistently, we observed clear differences in gene expression between early and late developmental transitions, with higher numbers of differentially expressed genes and fold changes around gastrulation. Furthermore, we identified three coexpression clusters that represented discrete gene expression patterns. During early transitions, transcriptional networks seemed to regulate cellular fate and morphogenesis of the larval body. In late transitions, these networks seemed to play important roles preparing planulae for switch in lifestyle and regulation of adult processes. Although developmental progression in A. digitifera is regulated to some extent by differential coexpression of well-defined gene networks, stage-specific transcription profiles appear to be independent entities. While negative regulation of transcription is predominant in early development, cell differentiation was upregulated in larval and adult stages. PMID:26941230

Impact of jamming on collective cell migration

NASA Astrophysics Data System (ADS)

Nnetu, Kenechukwu David; Knorr, Melanie; Pawlizak, Steve; Fuhs, Thomas; Zink, Mareike; KäS, Josef A.

2012-02-01

Multi-cellular migration plays an important role in physiological processes such as embryogenesis, cancer metastasis and tissue repair. During migration, single cells undergo cycles of extension, adhesion and retraction resulting in morphological changes. In a confluent monolayer, there are inter-cellular interactions and crowding, however, the impact of these interactions on the dynamics and elasticity of the monolayer at the multi-cellular and single cell level is not well understood. Here we study the dynamics of a confluent epithelial monolayer by simultaneously measuring cell motion at the multi-cellular and single cell level for various cell densities and tensile elasticity. At the multi-cellular level, the system exhibited spatial kinetic transitions from isotropic to anisotropic migration on long times and the velocity of the monolayer decreased with increasing cell density. Moreover, the dynamics was spatially and temporally heterogeneous. Interestingly, the dynamics was also heterogeneous in wound-healing assays and the correlation length was fitted by compressed exponential. On the single cell scale, we observed transient caging effects with increasing cage rearrangement times as the system age due to an increase in density. Also, the density dependent elastic modulus of the monolayer scaled as a weak power law. Together, these findings suggest that caging effects at the single cell level initiates a slow and heterogeneous dynamics at the multi-cellular level which is similar to the glassy dynamics of deformable colloidal systems.

Neural Progenitor Cells as Models for High-Throughput Screens of Developmental Neurotoxicity: State of the Science

EPA Science Inventory

In vitro, high-throughput approaches have been widely recommended as an approach to screen chemicals for the potential to cause developmental neurotoxicity and prioritize them for additional testing. The choice of cellular models for such an approach will have important ramificat...

77 FR 33474 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-06

... Translational Integrated Review Group; Cancer Molecular Pathobiology Study Section. Date: June 25-26, 2012. Time... 7818, Bethesda, MD 20892, 301-435- 1198, [email protected] . Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review Group; Cellular and Molecular Biology of...

75 FR 57475 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-21

... personal privacy. Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review Group; Cellular and Molecular Biology of Neurodegeneration Study Section. Date: October 14-15, 2010...; Collaborative: Behavioral Genetics and Epidemiology Linked Applications. Date: October 20-21, 2010. Time: 8:30 a...

75 FR 25273 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-07

... Genetics Integrated Review Group, Molecular Genetics C Study Section. Date: June 3-4, 2010. Time: 8 a.m. to... Committee: Oncology 1-Basic Translational Integrated Review Group, Cancer Molecular Pathobiology Study... Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review Group, Cellular and...

A Multi-Paradigm Modeling Framework to Simulate Dynamic Reciprocity in a Bioreactor

PubMed Central

Kaul, Himanshu; Cui, Zhanfeng; Ventikos, Yiannis

2013-01-01

Despite numerous technology advances, bioreactors are still mostly utilized as functional black-boxes where trial and error eventually leads to the desirable cellular outcome. Investigators have applied various computational approaches to understand the impact the internal dynamics of such devices has on overall cell growth, but such models cannot provide a comprehensive perspective regarding the system dynamics, due to limitations inherent to the underlying approaches. In this study, a novel multi-paradigm modeling platform capable of simulating the dynamic bidirectional relationship between cells and their microenvironment is presented. Designing the modeling platform entailed combining and coupling fully an agent-based modeling platform with a transport phenomena computational modeling framework. To demonstrate capability, the platform was used to study the impact of bioreactor parameters on the overall cell population behavior and vice versa. In order to achieve this, virtual bioreactors were constructed and seeded. The virtual cells, guided by a set of rules involving the simulated mass transport inside the bioreactor, as well as cell-related probabilistic parameters, were capable of displaying an array of behaviors such as proliferation, migration, chemotaxis and apoptosis. In this way the platform was shown to capture not only the impact of bioreactor transport processes on cellular behavior but also the influence that cellular activity wields on that very same local mass transport, thereby influencing overall cell growth. The platform was validated by simulating cellular chemotaxis in a virtual direct visualization chamber and comparing the simulation with its experimental analogue. The results presented in this paper are in agreement with published models of similar flavor. The modeling platform can be used as a concept selection tool to optimize bioreactor design specifications. PMID:23555740

SABRE: a bio-inspired fault-tolerant electronic architecture.

PubMed

Bremner, P; Liu, Y; Samie, M; Dragffy, G; Pipe, A G; Tempesti, G; Timmis, J; Tyrrell, A M

2013-03-01

As electronic devices become increasingly complex, ensuring their reliable, fault-free operation is becoming correspondingly more challenging. It can be observed that, in spite of their complexity, biological systems are highly reliable and fault tolerant. Hence, we are motivated to take inspiration for biological systems in the design of electronic ones. In SABRE (self-healing cellular architectures for biologically inspired highly reliable electronic systems), we have designed a bio-inspired fault-tolerant hierarchical architecture for this purpose. As in biology, the foundation for the whole system is cellular in nature, with each cell able to detect faults in its operation and trigger intra-cellular or extra-cellular repair as required. At the next level in the hierarchy, arrays of cells are configured and controlled as function units in a transport triggered architecture (TTA), which is able to perform partial-dynamic reconfiguration to rectify problems that cannot be solved at the cellular level. Each TTA is, in turn, part of a larger multi-processor system which employs coarser grain reconfiguration to tolerate faults that cause a processor to fail. In this paper, we describe the details of operation of each layer of the SABRE hierarchy, and how these layers interact to provide a high systemic level of fault tolerance.

A multi-model approach to nucleic acid-based drug development.

PubMed

Gautherot, Isabelle; Sodoyer, Regís

2004-01-01

With the advent of functional genomics and the shift of interest towards sequence-based therapeutics, the past decades have witnessed intense research efforts on nucleic acid-mediated gene regulation technologies. Today, RNA interference is emerging as a groundbreaking discovery, holding promise for development of genetic modulators of unprecedented potency. Twenty-five years after the discovery of antisense RNA and ribozymes, gene control therapeutics are still facing developmental difficulties, with only one US FDA-approved antisense drug currently available in the clinic. Limited predictability of target site selection models is recognized as one major stumbling block that is shared by all of the so-called complementary technologies, slowing the progress towards a commercial product. Currently employed in vitro systems for target site selection include RNAse H-based mapping, antisense oligonucleotide microarrays, and functional screening approaches using libraries of catalysts with randomized target-binding arms to identify optimal ribozyme/DNAzyme cleavage sites. Individually, each strategy has its drawbacks from a drug development perspective. Utilization of message-modulating sequences as therapeutic agents requires that their action on a given target transcript meets criteria of potency and selectivity in the natural physiological environment. In addition to sequence-dependent characteristics, other factors will influence annealing reactions and duplex stability, as well as nucleic acid-mediated catalysis. Parallel consideration of physiological selection systems thus appears essential for screening for nucleic acid compounds proposed for therapeutic applications. Cellular message-targeting studies face issues relating to efficient nucleic acid delivery and appropriate analysis of response. For reliability and simplicity, prokaryotic systems can provide a rapid and cost-effective means of studying message targeting under pseudo-cellular conditions, but such approaches also have limitations. To streamline nucleic acid drug discovery, we propose a multi-model strategy integrating high-throughput-adapted bacterial screening, followed by reporter-based and/or natural cellular models and potentially also in vitro assays for characterization of the most promising candidate sequences, before final in vivo testing.

Impaired activity of CCA-adding enzyme TRNT1 impacts OXPHOS complexes and cellular respiration in SIFD patient-derived fibroblasts.

PubMed

Liwak-Muir, Urszula; Mamady, Hapsatou; Naas, Turaya; Wylie, Quinlan; McBride, Skye; Lines, Matthew; Michaud, Jean; Baird, Stephen D; Chakraborty, Pranesh K; Holcik, Martin

2016-06-18

SIFD (Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay) is a novel form of congenital sideroblastic anemia associated with B-cell immunodeficiency, periodic fevers, and developmental delay caused by mutations in the CCA-adding enzyme TRNT1, but the precise molecular pathophysiology is not known. We show that the disease causing mutations in patient-derived fibroblasts do not affect subcellular localization of TRNT1 and show no gross morphological differences when compared to control cells. Analysis of cellular respiration and oxidative phosphorylation (OXPHOS) complexes demonstrates that both basal and maximal respiration rates are decreased in patient cells, which may be attributed to an observed decrease in the abundance of select proteins of the OXPHOS complexes. Our data provides further insight into cellular pathophysiology of SIFD.

77 FR 52751 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-30

... personal privacy. Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review Group, Molecular Neuropharmacology and Signaling Study Section. Date: September 24-25, 2012. Time: 8 a.m... 7770, Bethesda, MD 20892, (301) 435- 0684, [email protected] . Name of Committee: Molecular, Cellular...

Focus on Methodology: Salivary Bioscience and Research on Adolescence: An Integrated Perspective

ERIC Educational Resources Information Center

Granger, Douglas A.; Fortunato, Christine K.; Beltzer, Emilie K.; Virag, Marta; Bright, Melissa A.; Out, Dorothee

2012-01-01

The characterization of the salivary proteome and advances in biotechnology create an opportunity for developmental scientists to measure multi-level components of biological systems in oral fluids and identify relationships with developmental processes and behavioral and social forces. The implications for developmental science are profound…

Insects as test systems for assessing the potential role of microgravity in biological development and evolution

NASA Astrophysics Data System (ADS)

Vernós, I.; Carratalá, M.; González-Jurado, J.; Valverde, J. R.; Calleja, M.; Domingo, A.; Vinós, J.; Cervera, M.; Marco, R.

Gravity and radiation are undoubtedly the two major environmental factors altered in space. Gravity is a weak force, which creates a permanent potential field acting on the mass of biological systems and their cellular components, strongly reduced in space flights. Developmental systems, particularly at very early stages, provide the larger cellular compartments known, where the effects of alterations in the size of the gravity vector on living organisms can be more effectively tested. The insects, one of the more highly evolved classes of animals in which early development occurs in a syncytial embryo, are systems particularly well suited to test these effects and the specific developmental mechanisms affected. Furthermore, they share some basic features such as small size, short life cycles, relatively high radio-resistance, etc. and show a diversity of developmental strategies and tempos advantageous in experiments of this type in space. Drosophila melanogaster, the current biological paradigm to study development, with so much genetic and evolutionary background available, is clearly the reference organism for these studies. The current evidence on the effects of the physical parameters altered in space flights on insect development indicate a surprising correlation between effects seen on the fast developing and relatively small Drosophila embryo and the more slowly developing and large Carausius morosus system. In relation to the issue of the importance of developmental and environmental constraints in biological evolution, still the missing link in current evolutionary thinking, insects and space facilities for long-term experiments could provide useful experimental settings where to critically assess how development and evolution may be interconnected. Finally, it has to be pointed out that since there are experimental data indicating a possible synergism between microgravity and space radiation, possible effects of space radiation should be taken into account in the planning and evaluation of experiments designed to test the potential role of microgravity on biological development and evolution.

Security Policy and Infrastructure in the Context of a Multi-Centeric Information System Dedicated to Autism Spectrum Disorder.

PubMed

Ben Said, Mohamed; Robel, Laurence; Golse, Bernard; Jais, Jean Philippe

2017-01-01

Autism spectrum disorders (ASD) are complex neuro-developmental disorders affecting children in their early age. The diagnosis of ASD relies on multidisciplinary investigations, in psychiatry, neurology, genetics, electrophysiology, neuro-imagery, audiology and ophthalmology. In order to support clinicians, researchers and public health decision makers, we designed an information system dedicated to ASD, called TEDIS. TEDIS was designed to manage systematic, exhaustive and continuous multi-centric patient data collection via secured Internet connections. In this paper, we present the security policy and security infrastructure we developed to protect ASD' patients' clinical data and patients' privacy. We tested our system on 359 ASD patient records in a local secured intranet environment and showed that the security system is functional, with a consistent, transparent and safe encrypting-decrypting behavior. It is ready for deployment in the nine ASD expert assessment centers in the Ile de France district.

Grounding language in action and perception: From cognitive agents to humanoid robots

NASA Astrophysics Data System (ADS)

Cangelosi, Angelo

2010-06-01

In this review we concentrate on a grounded approach to the modeling of cognition through the methodologies of cognitive agents and developmental robotics. This work will focus on the modeling of the evolutionary and developmental acquisition of linguistic capabilities based on the principles of symbol grounding. We review cognitive agent and developmental robotics models of the grounding of language to demonstrate their consistency with the empirical and theoretical evidence on language grounding and embodiment, and to reveal the benefits of such an approach in the design of linguistic capabilities in cognitive robotic agents. In particular, three different models will be discussed, where the complexity of the agent's sensorimotor and cognitive system gradually increases: from a multi-agent simulation of language evolution, to a simulated robotic agent model for symbol grounding transfer, to a model of language comprehension in the humanoid robot iCub. The review also discusses the benefits of the use of humanoid robotic platform, and specifically of the open source iCub platform, for the study of embodied cognition.

Incorporating Religiosity into a Developmental Model of Positive Family Functioning across Generations

PubMed Central

Spilman, Sarah K.; Neppl, Tricia K.; Donnellan, M. Brent; Schofield, Thomas J.; Conger, Rand D.

2012-01-01

This study evaluated a developmental model of intergenerational continuity in religiosity and its association with observed competency in romantic and parent-child relationships across two generations. Using multi-informant data from the Family Transitions Project, a 20-year longitudinal study of families that began during early adolescence (N = 451), we found that parental religiosity assessed during the youth’s adolescence was positively related to the youth’s own religiosity during adolescence which, in turn, predicted their religiosity after the transition to adulthood. The findings also supported the theoretical model guiding the study, which proposes that religiosity acts as a personal resource that will be uniquely and positively associated with the quality of family relationships. Especially important, the findings demonstrate support for the role of religiosity in a developmental process that promotes positive family functioning after addressing earlier methodological limitations in this area of study, such as cross-sectional research designs, single informant measurement, retrospective reports, and the failure to control for other individual differences. PMID:22545832

Incubation period and immune function: A comparative field study among coexisting birds

USGS Publications Warehouse

Palacios, M.G.; Martin, T.E.

2006-01-01

Developmental periods are integral components of life history strategies that can have important fitness consequences and vary enormously among organisms. However, the selection pressures and mechanisms causing variation in length of developmental periods are poorly understood. Particularly puzzling are prolonged developmental periods, because their selective advantage is unclear. Here we tested the hypotheses that immune function is stronger in species that are attacked at a higher rate by parasites and that prolonged embryonic development allows the development of this stronger immune system. Through a comparative field study among 12 coexisting passerine bird species, we show that species with higher blood parasite prevalence mounted stronger cellular immune responses than species with lower prevalence. These results provide support for the hypothesis that species facing greater selection pressure from parasites invest more in immune function. However, species with longer incubation periods mounted weaker cellular immune responses than species with shorter periods. Therefore, cellular immune responses do not support the hypothesis that longer development time enhances immunocompentence. Future studies should assess other components of the immune system and test alternative causes of variation in incubation periods among bird species. ?? Springer-Verlag 2005.

A knock-in mouse line conditionally expressing the tumor suppressor WTX/AMER1.

PubMed

Boutet, Agnès; Comai, Glenda; Charlet, Aurélie; Jian Motamedi, Fariba; Dhib, Haroun; Bandiera, Roberto; Schedl, Andreas

2017-11-01

WTX/AMER1 is an important developmental regulator, mutations in which have been identified in a proportion of patients suffering from the renal neoplasm Wilms' tumor and in the bone malformation syndrome Osteopathia Striata with Cranial Sclerosis (OSCS). Its cellular functions appear complex and the protein can be found at the membrane, within the cytoplasm and the nucleus. To understand its developmental and cellular function an allelic series for Wtx in the mouse is crucial. Whereas mice carrying a conditional knock out allele for Wtx have been previously reported, a gain-of-function mouse model that would allow studying the molecular, cellular and developmental role of Wtx is still missing. Here we describe the generation of a novel mouse strain that permits the conditional activation of WTX expression. Wtx fused to GFP was introduced downstream a stop cassette flanked by loxP sites into the Rosa26 locus by gene targeting. Ectopic WTX expression is reported after crosses with several Cre transgenic mice in different embryonic tissues. Further, functionality of the fusion protein was demonstrated in the context of a Wtx null allele. © 2017 Wiley Periodicals, Inc.

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

PubMed

Engh, Ines; Nowrousian, Minou; Kück, Ulrich

2010-12-01

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

Application of Targeted Functional Assays to Assess a Putative Vascular Disruption Developmental Toxicity Pathway Informed By ToxCast High-Throughput Screening Data

EPA Science Inventory

Chemical perturbation of vascular development is a putative toxicity pathway which may result in developmental toxicity. EPA’s high-throughput screening (HTS) ToxCast program contains assays which measure cellular signals and biological processes critical for blood vessel develop...

Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus

EPA Science Inventory

Title (20 words): Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus. Introduction (120 words): Polybrominated diphenyl ethers (PBDE5) possess neurotoxic effects similar to those of PCBs. The cellular a...

Long-Term Growth of Moss in Microfluidic Devices Enables Subcellular Studies in Development.

PubMed

Bascom, Carlisle S; Wu, Shu-Zon; Nelson, Katherine; Oakey, John; Bezanilla, Magdalena

2016-09-01

Key developmental processes that occur on the subcellular and cellular level or occur in occluded tissues are difficult to access, let alone image and analyze. Recently, culturing living samples within polydimethylsiloxane (PDMS) microfluidic devices has facilitated the study of hard-to-reach developmental events. Here, we show that an early diverging land plant, Physcomitrella patens, can be continuously cultured within PDMS microfluidic chambers. Because the PDMS chambers are bonded to a coverslip, it is possible to image P. patens development at high resolution over long time periods. Using PDMS chambers, we report that wild-type protonemal tissue grows at the same rate as previously reported for growth on solid medium. Using long-term imaging, we highlight key developmental events, demonstrate compatibility with high-resolution confocal microscopy, and obtain growth rates for a slow-growing mutant. By coupling the powerful genetic tools available to P. patens with long-term growth and imaging provided by PDMS microfluidic chambers, we demonstrate the capability to study cellular and subcellular developmental events in plants directly and in real time. © 2016 American Society of Plant Biologists. All rights reserved.

76 FR 57066 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-15

... personal privacy. Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review, Group, Cellular and Molecular Biology of Glia Study Section. Date: October 14, 2011. Time: 8 a.m. to 7... Domestic Assistance Program Nos. 93.306, Comparative Medicine; 93.333, Clinical Research, 93.306, 93.333...

75 FR 25275 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-07

...; Molecular Genetics B Study Section. Date: June 1-2, 2010. Time: 8 a.m. to 5 p.m. Agenda: To review and...-435- 1180, [email protected] . Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review Group; Cellular and Molecular Biology of Neurodegeneration Study Section. Date...

Developmental Change and Intraindividual Variability: Relating Cognitive Aging to Cognitive Plasticity, Cardiovascular Lability, and Emotional Diversity

PubMed Central

Ram, Nilam; Gerstorf, Denis; Lindenberger, Ulman; Smith, Jacqui

2010-01-01

Repeated assessments obtained over years can be used to measure individuals’ developmental change, whereas repeated assessments obtained over a few weeks can be used to measure individuals’ dynamic characteristics. Using data from a burst of measurement embedded in the Berlin Aging Study (BASE: Baltes & Mayer, 1999), we illustrate and examine how long-term changes in cognitive ability are related to short-term changes in cognitive performance, cardiovascular function, and emotional experience. Our findings suggest that “better” cognitive aging over approximately13 years was associated with greater cognitive plasticity, less cardiovascular lability, and less emotional diversity over approximately 2 weeks at age 90 years. The study highlights the potential benefits of multi-time scale longitudinal designs for the study of individual function and development. PMID:21443355

Developmental psycholinguistics teaches us that we need multi-method, not single-method, approaches to the study of linguistic representation.

PubMed

Rowland, Caroline F; Monaghan, Padraic

2017-01-01

In developmental psycholinguistics, we have, for many years, been generating and testing theories that propose both descriptions of adult representations and explanations of how those representations develop. We have learnt that restricting ourselves to any one methodology yields only incomplete data about the nature of linguistic representations. We argue that we need a multi-method approach to the study of representation.

Salt gland distribution in limonium bicolor at the individual level

NASA Astrophysics Data System (ADS)

Leng, B. Y.; Yuan, F.; Dong, X. X.; Wang, B. S.

2018-02-01

Limonium bicolor is a typical exo-recretohalophyte with multi-cellular salt glands. A differential interference contrast (DIC) microscope were applied to investigate the pattern of salt gland distribution in L. bicolor at the individual level. For a single mature leaf, more salt glands are distributed in the leaf central and apical regions than leaf base. For the leaves in different developmental stages, firstly, the density of salt glands linearly decreased at the beginning of leaf expansion and kept a relatively constant value in the later periods, which was mainly due to the rapid expansion of epidermal cells. Secondly, the total number of glands per leaf showed a reversed trend compared to the density of salt glands. These results suggested that the salt gland density was adapted to the leaf age and area as more and more salt accumulated in the saline soils.

Anticancer Molecular Mechanisms of Resveratrol

PubMed Central

Varoni, Elena M.; Lo Faro, Alfredo Fabrizio; Sharifi-Rad, Javad; Iriti, Marcello

2016-01-01

Resveratrol is a pleiotropic phytochemical belonging to the stilbene family. Though it is only significantly present in grape products, a huge amount of preclinical studies investigated its anticancer properties in a plethora of cellular and animal models. Molecular mechanisms of resveratrol involved signaling pathways related to extracellular growth factors and receptor tyrosine kinases; formation of multiprotein complexes and cell metabolism; cell proliferation and genome instability; cytoplasmic tyrosine kinase signaling (cytokine, integrin, and developmental pathways); signal transduction by the transforming growth factor-β super-family; apoptosis and inflammation; and immune surveillance and hormone signaling. Resveratrol also showed a promising role to counteract multidrug resistance: in adjuvant therapy, associated with 5-fluoruracyl and cisplatin, resveratrol had additive and/or synergistic effects increasing the chemosensitization of cancer cells. Resveratrol, by acting on diverse mechanisms simultaneously, has been emphasized as a promising, multi-target, anticancer agent, relevant in both cancer prevention and treatment. PMID:27148534

Anticancer Molecular Mechanisms of Resveratrol.

PubMed

Varoni, Elena M; Lo Faro, Alfredo Fabrizio; Sharifi-Rad, Javad; Iriti, Marcello

2016-01-01

Resveratrol is a pleiotropic phytochemical belonging to the stilbene family. Though it is only significantly present in grape products, a huge amount of preclinical studies investigated its anticancer properties in a plethora of cellular and animal models. Molecular mechanisms of resveratrol involved signaling pathways related to extracellular growth factors and receptor tyrosine kinases; formation of multiprotein complexes and cell metabolism; cell proliferation and genome instability; cytoplasmic tyrosine kinase signaling (cytokine, integrin, and developmental pathways); signal transduction by the transforming growth factor-β super-family; apoptosis and inflammation; and immune surveillance and hormone signaling. Resveratrol also showed a promising role to counteract multidrug resistance: in adjuvant therapy, associated with 5-fluoruracyl and cisplatin, resveratrol had additive and/or synergistic effects increasing the chemosensitization of cancer cells. Resveratrol, by acting on diverse mechanisms simultaneously, has been emphasized as a promising, multi-target, anticancer agent, relevant in both cancer prevention and treatment.

The Human Cell Atlas.

PubMed

Regev, Aviv; Teichmann, Sarah A; Lander, Eric S; Amit, Ido; Benoist, Christophe; Birney, Ewan; Bodenmiller, Bernd; Campbell, Peter; Carninci, Piero; Clatworthy, Menna; Clevers, Hans; Deplancke, Bart; Dunham, Ian; Eberwine, James; Eils, Roland; Enard, Wolfgang; Farmer, Andrew; Fugger, Lars; Göttgens, Berthold; Hacohen, Nir; Haniffa, Muzlifah; Hemberg, Martin; Kim, Seung; Klenerman, Paul; Kriegstein, Arnold; Lein, Ed; Linnarsson, Sten; Lundberg, Emma; Lundeberg, Joakim; Majumder, Partha; Marioni, John C; Merad, Miriam; Mhlanga, Musa; Nawijn, Martijn; Netea, Mihai; Nolan, Garry; Pe'er, Dana; Phillipakis, Anthony; Ponting, Chris P; Quake, Stephen; Reik, Wolf; Rozenblatt-Rosen, Orit; Sanes, Joshua; Satija, Rahul; Schumacher, Ton N; Shalek, Alex; Shapiro, Ehud; Sharma, Padmanee; Shin, Jay W; Stegle, Oliver; Stratton, Michael; Stubbington, Michael J T; Theis, Fabian J; Uhlen, Matthias; van Oudenaarden, Alexander; Wagner, Allon; Watt, Fiona; Weissman, Jonathan; Wold, Barbara; Xavier, Ramnik; Yosef, Nir

2017-12-05

The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.

The Human Cell Atlas

PubMed Central

Amit, Ido; Benoist, Christophe; Birney, Ewan; Bodenmiller, Bernd; Campbell, Peter; Carninci, Piero; Clatworthy, Menna; Clevers, Hans; Deplancke, Bart; Dunham, Ian; Eberwine, James; Eils, Roland; Enard, Wolfgang; Farmer, Andrew; Fugger, Lars; Göttgens, Berthold; Hacohen, Nir; Haniffa, Muzlifah; Hemberg, Martin; Kim, Seung; Klenerman, Paul; Kriegstein, Arnold; Lein, Ed; Linnarsson, Sten; Lundberg, Emma; Lundeberg, Joakim; Majumder, Partha; Marioni, John C; Merad, Miriam; Mhlanga, Musa; Nawijn, Martijn; Netea, Mihai; Nolan, Garry; Pe'er, Dana; Phillipakis, Anthony; Ponting, Chris P; Quake, Stephen; Reik, Wolf; Rozenblatt-Rosen, Orit; Sanes, Joshua; Satija, Rahul; Schumacher, Ton N; Shalek, Alex; Shapiro, Ehud; Sharma, Padmanee; Shin, Jay W; Stegle, Oliver; Stratton, Michael; Stubbington, Michael J T; Theis, Fabian J; Uhlen, Matthias; van Oudenaarden, Alexander; Wagner, Allon; Watt, Fiona; Weissman, Jonathan; Wold, Barbara; Xavier, Ramnik; Yosef, Nir

2017-01-01

The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community. PMID:29206104

The Molecular Timeline of a Reviving Bacterial Spore

PubMed Central

Sinai, Lior; Rosenberg, Alex; Smith, Yoav; Segev, Einat; Ben-Yehuda, Sigal

2015-01-01

Summary The bacterial spore can rapidly convert from a dormant to a fully active cell. Here we study this remarkable cellular transition in Bacillus subtilis and reveal the identity of the newly synthesized proteins throughout spore revival. Our analysis uncovers a highly ordered developmental program that correlates with the spore morphological changes and reveals the spatial and temporal molecular events fundamental to reconstruct a cell. As opposed to current knowledge, we found that translation takes place during the earliest revival event, termed germination, a process hitherto considered to occur without the need for any macromolecule synthesis. Furthermore, we demonstrate that translation is required for execution of germination and relies on the bona fide translational factors RpmE and Tig. Our study sheds light on the spore revival process and on the vital building blocks underlying cellular awakening, thereby paving the way for designing new antimicrobial agents to eradicate spore-forming pathogens. PMID:25661487

Environmental pollutants and lifestyle factors induce oxidative stress and poor prenatal development.

PubMed

Al-Gubory, Kaïs H

2014-07-01

Developmental toxicity caused by exposure to a mixture of environmental pollutants has become a major health concern. Human-made chemicals, including xenoestrogens, pesticides and heavy metals, as well as unhealthy lifestyle behaviours, mainly tobacco smoking, alcohol consumption and medical drug abuse, are major factors that adversely influence prenatal development and increase susceptibility of offspring to diseases. There is evidence to suggest that the developmental toxicological mechanisms of chemicals and lifestyle factors involve the generation of reactive oxygen species (ROS) and cellular oxidative damage. Overproduction of ROS induces oxidative stress, a state where increased ROS generation overwhelms antioxidant protection and subsequently leads to oxidative damage of cellular macromolecules. Data on the involvement of oxidative stress in the mechanism of developmental toxicity following exposure to environmental pollutants are reviewed in an attempt to provide an updated basis for future studies on the toxic effect of such pollutants, particularly the notion of increased risk for developmental toxicity due to combined and cumulative exposure to various environmental pollutants. The aims of such studies are to better understand the mechanisms by which environmental pollutants adversely affect conceptus development and to elucidate the impact of cumulative exposures to multiple pollutants on post-natal development and health outcomes. Developmental toxicity caused by exposure to mixture of environmental pollutants has become a major health concern. Human-made chemicals, including xenoestrogens, pesticides and heavy metals, as well as unhealthy lifestyle behaviors, mainly tobacco smoking, alcohol consumption and medical drug abuse, are major factors that adversely influence prenatal development and increase the susceptibility of offspring to development complications and diseases. There is evidence to suggest that the developmental toxicological mechanisms of human-made chemicals and unhealthy lifestyle factors involve the generation of reactive oxygen species (ROS) and cellular oxidative damage. Overproduction of ROS induces oxidative stress, a state where increased generation of ROS overwhelms antioxidant protection and subsequently leads to oxidative damage of cellular macromolecules. Exposure to various environmental pollutants induces synergic and cumulative dose-additive adverse effects on prenatal development, pregnancy outcomes and neonate health. Data from the literature on the involvement of oxidative stress in the mechanism of developmental toxicity following in vivo exposure to environmental pollutants will be reviewed in an attempt to provide an updated basis for future studies on the toxic effect of such pollutants, particularly the notion of increased risk for developmental toxicity due to combined and cumulative exposure to various environmental pollutants. The aims of such studies are to better understand the mechanisms by which environmental pollutants adversely affect conceptus development and to elucidate the impact of cumulative exposures to multiple pollutants on postnatal development and health outcomes. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

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.

417th Brookhaven Lecture

ScienceCinema

Huilin Li

2017-12-09

Proteins that cleave other proteins using a molecule of water, protease complexes are exquisite macromolecular machines involved in a multitude of physiological and cellular reactions. Our structural studies shed light into the inner workings of multi-protein assemblies, and they reveal a surprisingly common strategy for controlled proteolysis employed by the two drastically different machines. Further research will facilitate rational design of drugs for treating Tb infection and Alzheimer's disease.

Making quantitative morphological variation from basic developmental processes: where are we? The case of the Drosophila wing

PubMed Central

Alexis, Matamoro-Vidal; Isaac, Salazar-Ciudad; David, Houle

2015-01-01

One of the aims of evolutionary developmental biology is to discover the developmental origins of morphological variation. The discipline has mainly focused on qualitative morphological differences (e.g., presence or absence of a structure) between species. Studies addressing subtle, quantitative variation are less common. The Drosophila wing is a model for the study of development and evolution, making it suitable to investigate the developmental mechanisms underlying the subtle quantitative morphological variation observed in nature. Previous reviews have focused on the processes involved in wing differentiation, patterning and growth. Here, we investigate what is known about how the wing achieves its final shape, and what variation in development is capable of generating the variation in wing shape observed in nature. Three major developmental stages need to be considered: larval development, pupariation, and pupal development. The major cellular processes involved in the determination of tissue size and shape are cell proliferation, cell death, oriented cell division and oriented cell intercalation. We review how variation in temporal and spatial distribution of growth and transcription factors affects these cellular mechanisms, which in turn affects wing shape. We then discuss which aspects of the wing morphological variation are predictable on the basis of these mechanisms. PMID:25619644

Engineering cellular fibers for musculoskeletal soft tissues using directed self-assembly.

PubMed

Schiele, Nathan R; Koppes, Ryan A; Chrisey, Douglas B; Corr, David T

2013-05-01

Engineering strategies guided by developmental biology may enhance and accelerate in vitro tissue formation for tissue engineering and regenerative medicine applications. In this study, we looked toward embryonic tendon development as a model system to guide our soft tissue engineering approach. To direct cellular self-assembly, we utilized laser micromachined, differentially adherent growth channels lined with fibronectin. The micromachined growth channels directed human dermal fibroblast cells to form single cellular fibers, without the need for a provisional three-dimensional extracellular matrix or scaffold to establish a fiber structure. Therefore, the resulting tissue structure and mechanical characteristics were determined solely by the cells. Due to the self-assembly nature of this approach, the growing fibers exhibit some key aspects of embryonic tendon development, such as high cellularity, the rapid formation (within 24 h) of a highly organized and aligned cellular structure, and the expression of cadherin-11 (indicating direct cell-to-cell adhesions). To provide a dynamic mechanical environment, we have also developed and characterized a method to apply precise cyclic tensile strain to the cellular fibers as they develop. After an initial period of cellular fiber formation (24 h postseeding), cyclic strain was applied for 48 h, in 8-h intervals, with tensile strain increasing from 0.7% to 1.0%, and at a frequency of 0.5 Hz. Dynamic loading dramatically increased cellular fiber mechanical properties with a nearly twofold increase in both the linear region stiffness and maximum load at failure, thereby demonstrating a mechanism for enhancing cellular fiber formation and mechanical properties. Tissue engineering strategies, designed to capture key aspects of embryonic development, may provide unique insight into accelerated maturation of engineered replacement tissue, and offer significant advances for regenerative medicine applications in tendon, ligament, and other fibrous soft tissues.

76 FR 26736 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-09

... due to the timing limitations imposed by the review and funding cycle. Name of Committee: Molecular....gov . Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review Group, Cellular and Molecular Biology of Glia Study Section. Date: June 2-3, 2011. Time: 8 a.m. to 4 p.m. Agenda...

78 FR 59361 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-26

... Review Group; Molecular Genetics A Study Section. Date: October 21-22, 2013. Time: 8:30 a.m. to 1:30 p.m...-435- 0681, [email protected] . Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review Group; Cellular and Molecular Biology of Glia Study Section. Date: October 21, 2013. Time...

Multi-Hop Link Capacity of Multi-Route Multi-Hop MRC Diversity for a Virtual Cellular Network

NASA Astrophysics Data System (ADS)

Daou, Imane; Kudoh, Eisuke; Adachi, Fumiyuki

In virtual cellular network (VCN), proposed for high-speed mobile communications, the signal transmitted from a mobile terminal is received by some wireless ports distributed in each virtual cell and relayed to the central port that acts as a gateway to the core network. In this paper, we apply the multi-route MHMRC diversity in order to decrease the transmit power and increase the multi-hop link capacity. The transmit power, the interference power and the link capacity are evaluated for DS-CDMA multi-hop VCN by computer simulation. The multi-route MHMRC diversity can be applied to not only DS-CDMA but also other access schemes (i. e. MC-CDMA, OFDM, etc.).

Diagnostic Classification 0-3: Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood.

ERIC Educational Resources Information Center

Zero to Three: National Center for Infants, Toddlers and Families, Washington, DC.

The diagnostic framework presented in this manual seeks to address the need for a systematic, multi-disciplinary, developmentally based approach to the classification of mental health and developmental difficulties in the first 4 years of life. An introduction discusses clinical approaches to assessment and diagnosis, gives an overview of the…

Developmental and Spatial Expression of sir2 Genes in the Cellular Slime Mold Dictyostelium discoideum.

PubMed

Katayama, Takahiro; Yasukawa, Hiro

2008-01-01

The cellular slime mold Dictyostelium discoideum grows as unicellular free-living amoebae in the presence of nutrients. Upon starvation, the amoebae aggregate and form multicellular structures that each consist of a stalk and spores. D. discoideum encodes at least four proteins (Sir2A, Sir2B, Sir2C, and Sir2D) homologous to human SIRT. RT-PCR and WISH analyses showed that the genes for Sir2A, Sir2C, and Sir2D were expressed at high levels in growing cells but at decreased levels in developing cells, whereas the gene encoding Sir2B was expressed in the prestalk-cell region in the developmental phase.

Multivariate synaptic and behavioral profiling reveals new developmental endophenotypes in the prefrontal cortex

PubMed Central

Iafrati, Jillian; Malvache, Arnaud; Gonzalez Campo, Cecilia; Orejarena, M. Juliana; Lassalle, Olivier; Bouamrane, Lamine; Chavis, Pascale

2016-01-01

The postnatal maturation of the prefrontal cortex (PFC) represents a period of increased vulnerability to risk factors and emergence of neuropsychiatric disorders. To disambiguate the pathophysiological mechanisms contributing to these disorders, we revisited the endophenotype approach from a developmental viewpoint. The extracellular matrix protein reelin which contributes to cellular and network plasticity, is a risk factor for several psychiatric diseases. We mapped the aggregate effect of the RELN risk allele on postnatal development of PFC functions by cross-sectional synaptic and behavioral analysis of reelin-haploinsufficient mice. Multivariate analysis of bootstrapped datasets revealed subgroups of phenotypic traits specific to each maturational epoch. The preeminence of synaptic AMPA/NMDA receptor content to pre-weaning and juvenile endophenotypes shifts to long-term potentiation and memory renewal during adolescence followed by NMDA-GluN2B synaptic content in adulthood. Strikingly, multivariate analysis shows that pharmacological rehabilitation of reelin haploinsufficient dysfunctions is mediated through induction of new endophenotypes rather than reversion to wild-type traits. By delineating previously unknown developmental endophenotypic sequences, we conceived a promising general strategy to disambiguate the molecular underpinnings of complex psychiatric disorders and for the rational design of pharmacotherapies in these disorders. PMID:27765946

Quantifying Cell Fate Decisions for Differentiation and Reprogramming of a Human Stem Cell Network: Landscape and Biological Paths

PubMed Central

Li, Chunhe; Wang, Jin

2013-01-01

Cellular reprogramming has been recently intensively studied experimentally. We developed a global potential landscape and kinetic path framework to explore a human stem cell developmental network composed of 52 genes. We uncovered the underlying landscape for the stem cell network with two basins of attractions representing stem and differentiated cell states, quantified and exhibited the high dimensional biological paths for the differentiation and reprogramming process, connecting the stem cell state and differentiated cell state. Both the landscape and non-equilibrium curl flux determine the dynamics of cell differentiation jointly. Flux leads the kinetic paths to be deviated from the steepest descent gradient path, and the corresponding differentiation and reprogramming paths are irreversible. Quantification of paths allows us to find out how the differentiation and reprogramming occur and which important states they go through. We show the developmental process proceeds as moving from the stem cell basin of attraction to the differentiation basin of attraction. The landscape topography characterized by the barrier heights and transition rates quantitatively determine the global stability and kinetic speed of cell fate decision process for development. Through the global sensitivity analysis, we provided some specific predictions for the effects of key genes and regulation connections on the cellular differentiation or reprogramming process. Key links from sensitivity analysis and biological paths can be used to guide the differentiation designs or reprogramming tactics. PMID:23935477

Protein interference applications in cellular and developmental biology using DARPins that recognize GFP and mCherry

PubMed Central

Brauchle, Michael; Hansen, Simon; Caussinus, Emmanuel; Lenard, Anna; Ochoa-Espinosa, Amanda; Scholz, Oliver; Sprecher, Simon G.; Plückthun, Andreas; Affolter, Markus

2014-01-01

ABSTRACT Protein–protein interactions are crucial for cellular homeostasis and play important roles in the dynamic execution of biological processes. While antibodies represent a well-established tool to study protein interactions of extracellular domains and secreted proteins, as well as in fixed and permeabilized cells, they usually cannot be functionally expressed in the cytoplasm of living cells. Non-immunoglobulin protein-binding scaffolds have been identified that also function intracellularly and are now being engineered for synthetic biology applications. Here we used the Designed Ankyrin Repeat Protein (DARPin) scaffold to generate binders to fluorescent proteins and used them to modify biological systems directly at the protein level. DARPins binding to GFP or mCherry were selected by ribosome display. For GFP, binders with KD as low as 160 pM were obtained, while for mCherry the best affinity was 6 nM. We then verified in cell culture their specific binding in a complex cellular environment and found an affinity cut-off in the mid-nanomolar region, above which binding is no longer detectable in the cell. Next, their binding properties were employed to change the localization of the respective fluorescent proteins within cells. Finally, we performed experiments in Drosophila melanogaster and Danio rerio and utilized these DARPins to either degrade or delocalize fluorescently tagged fusion proteins in developing organisms, and to phenocopy loss-of-function mutations. Specific protein binders can thus be selected in vitro and used to reprogram developmental systems in vivo directly at the protein level, thereby bypassing some limitations of approaches that function at the DNA or the RNA level. PMID:25416061

PLAY HANDS PROTECTIVE GLOVES: TECHNICAL NOTE ON DESIGN AND CONCEPT.

PubMed

Houston-Hicks, Michele; Lura, Derek J; Highsmith, M Jason

2016-09-01

Cerebral Palsy (CP) is the leading cause of childhood motor disability, with a global incidence of 1.6 to 2.5/1,000 live births. Approximately 23% of children with CP are dependent upon assistive technologies. Some children with developmental disabilities have self-injurious behaviors such as finger biting but also have therapeutic needs. The purpose of this technical note is to describe design considerations for a protective glove and finger covering that maintains finger dexterity for children who exhibit finger and hand chewing (dermatophagia) and require therapeutic range of motion and may benefit from sensory stimulation resulting from constant contact between glove and skin. Protecting Little and Adolescent Youth (PLAY) Hands are protective gloves for children with developmental disorders such as CP who injure themselves by biting their hands due to pain or sensory issues. PLAY Hands will be cosmetically appealing gloves that provide therapeutic warmth, tactile sensory feedback, range of motion for donning/ doffing, and protection to maximize function and quality of life for families of children with developmental disorders. The technology is either a per-finger protective orthosis or an entire glove solution designed from durable 3D-printed biodegradable/bioabsorbable materials such as thermoplastics. PLAY Hands represent a series of protective hand wear interventions in the areas of self-mutilating behavior, kinematics, and sensation. They will be made available in a range of protective iterations from single- or multi-digit finger orthoses to a basic glove design to a more structurally robust and protective iteration. To improve the quality of life for patients and caregivers, they are conceptualized to be cosmetically appealing, protective, and therapeutic.

An integrative review of ethnic and cultural variation in socialization and children's self-regulation.

PubMed

LeCuyer, Elizabeth A; Zhang, Yi

2015-04-01

To examine the evidence for cross-cultural variation in socialization and children's normative self-regulation, based on a contextual-developmental perspective. Nurses and healthcare workers in multi-cultural societies must understand diversity in socializing influences (including parenting) and in children's behaviour. A contextual-developmental perspective implies that normative cultural and ethnic values will influence socializing processes and behaviour, which in turn will influence children's self-regulation. Integrative review. Studies were located using five major search engines from 1990-2011. Domains of a contextual-developmental perspective and a comprehensive definition of self-regulation assisted the generation of search terms. Selected studies compared at least two ethnic or cultural groups and addressed contextual-developmental domains: (1) culturally specific social values, beliefs, or attitudes; (2) socializing behaviours; and (3) children's normative self-regulation. Eleven studies about children's self-regulation were found to have data consistent with a contextual-developmental perspective. Studies used descriptive correlational or comparative designs with primarily convenience sampling; eight confirmed stated hypotheses, three were exploratory. Findings across studies evidenced coherent patterns of sociocultural influence on children's attention, compliance, delay of gratification, effortful control and executive function. A contextual-developmental perspective provided a useful perspective to examine normative differences in values, socializing behaviours and children's self-regulation. This perspective and these findings are expected to guide future research, to assist nurses and healthcare providers to understand diversity in parenting and children's behaviour. © 2014 John Wiley & Sons Ltd.

The Genetic Precursors and the Advantageous and Disadvantageous Sequelae of Inhibited Temperament: An Evolutionary Perspective

PubMed Central

Davies, Patrick T.; Cicchetti, Dante; and, Rochelle F. Hentges; Sturge-Apple, Melissa L.

2014-01-01

Guided by evolutionary game theory (Korte, Koolhaas, Wingfield, & McEwen, 2005), this study aimed to identify the genetic precursors and the psychosocial sequelae of inhibited temperament in a sociodemographically disadvantaged and racially diverse sample of 201 two-year-old children who experienced elevated levels of domestic violence. Using a multi-method, prospective design across three annual measurement occasions, SEM analyses indicated that trained observer ratings of inhibited temperament at age two were uniquely predicted by polymorphisms in dopamine and serotonin transporter genes. Children's inhibited temperament, in turn, indirectly predicted decreases in their externalizing problems at age four through its association with greater behavioral flexibility at three years of age. Results highlight the value of integrating evolutionary and developmental conceptualizations in more comprehensively charting the developmental cascades of inhibited temperament. PMID:23527493

Rethinking developmental toxicity testing: Evolution or revolution?

PubMed

Scialli, Anthony R; Daston, George; Chen, Connie; Coder, Prägati S; Euling, Susan Y; Foreman, Jennifer; Hoberman, Alan M; Hui, Julia; Knudsen, Thomas; Makris, Susan L; Morford, LaRonda; Piersma, Aldert H; Stanislaus, Dinesh; Thompson, Kary E

2018-06-01

Current developmental toxicity testing adheres largely to protocols suggested in 1966 involving the administration of test compound to pregnant laboratory animals. After more than 50 years of embryo-fetal development testing, are we ready to consider a different approach to human developmental toxicity testing? A workshop was held under the auspices of the Developmental and Reproductive Toxicology Technical Committee of the ILSI Health and Environmental Sciences Institute to consider how we might design developmental toxicity testing if we started over with 21st century knowledge and techniques (revolution). We first consider what changes to the current protocols might be recommended to make them more predictive for human risk (evolution). The evolutionary approach includes modifications of existing protocols and can include humanized models, disease models, more accurate assessment and testing of metabolites, and informed approaches to dose selection. The revolution could start with hypothesis-driven testing where we take what we know about a compound or close analog and answer specific questions using targeted experimental techniques rather than a one-protocol-fits-all approach. Central to the idea of hypothesis-driven testing is the concept that testing can be done at the level of mode of action. It might be feasible to identify a small number of key events at a molecular or cellular level that predict an adverse outcome and for which testing could be performed in vitro or in silico or, rarely, using limited in vivo models. Techniques for evaluating these key events exist today or are in development. Opportunities exist for refining and then replacing current developmental toxicity testing protocols using techniques that have already been developed or are within reach. © 2018 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.

A Multi-Metric Assessment on the Impact of I Can Learn[R] (ICL) Multimedia on Actual and Perceived Student Achievement in Developmental Mathematics

ERIC Educational Resources Information Center

Stokes, Sandra D.

2011-01-01

This quasi-experimental study focused on the initiatives undertaken by a community college's Academic Skills Enhancement Program (ASEP) commonly known as the Developmental Education Department to find an alternative delivery method to aid its students in learning developmental mathematics. Moreover, this study (1) conducted a comparative…

FishFace: interactive atlas of zebrafish craniofacial development at cellular resolution

PubMed Central

2013-01-01

Background The vertebrate craniofacial skeleton may exhibit anatomical complexity and diversity, but its genesis and evolution can be understood through careful dissection of developmental programs at cellular resolution. Resources are lacking that include introductory overviews of skeletal anatomy coupled with descriptions of craniofacial development at cellular resolution. In addition to providing analytical guidelines for other studies, such an atlas would suggest cellular mechanisms underlying development. Description We present the Fish Face Atlas, an online, 3D-interactive atlas of craniofacial development in the zebrafish Danio rerio. Alizarin red-stained skulls scanned by fluorescent optical projection tomography and segmented into individual elements provide a resource for understanding the 3D structure of the zebrafish craniofacial skeleton. These data provide the user an anatomical entry point to confocal images of Alizarin red-stained zebrafish with transgenically-labelled pharyngeal arch ectomesenchyme, chondrocytes, and osteoblasts, which illustrate the appearance, morphogenesis, and growth of the mandibular and hyoid cartilages and bones, as viewed in live, anesthetized zebrafish during embryonic and larval development. Confocal image stacks at high magnification during the same stages provide cellular detail and suggest developmental and evolutionary hypotheses. Conclusion The FishFace Atlas is a novel learning tool for understanding craniofacial skeletal development, and can serve as a reference for a variety of studies, including comparative and mutational analyses. PMID:23714426

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

A High-Performance Cellular Automaton Model of Tumor Growth with Dynamically Growing Domains

PubMed Central

Poleszczuk, Jan; Enderling, Heiko

2014-01-01

Tumor growth from a single transformed cancer cell up to a clinically apparent mass spans many spatial and temporal orders of magnitude. Implementation of cellular automata simulations of such tumor growth can be straightforward but computing performance often counterbalances simplicity. Computationally convenient simulation times can be achieved by choosing appropriate data structures, memory and cell handling as well as domain setup. We propose a cellular automaton model of tumor growth with a domain that expands dynamically as the tumor population increases. We discuss memory access, data structures and implementation techniques that yield high-performance multi-scale Monte Carlo simulations of tumor growth. We discuss tumor properties that favor the proposed high-performance design and present simulation results of the tumor growth model. We estimate to which parameters the model is the most sensitive, and show that tumor volume depends on a number of parameters in a non-monotonic manner. PMID:25346862

[Developmental disorders in adulthood: concept, differential diagnosis, and treatment].

PubMed

Honda, Hideo

2014-01-01

The number of cases diagnosed with developmental disorders is rapidly increasing among those consulting psychiatry clinics for the first time in their adulthood. The author presents the concept of developmental disorders, discusses how they can be differentiated from other psychiatric disorders, and proposes some treatments. From now on, all psychiatrists should know the difference between developmental disorders and other psychiatric disorders, and diagnose them multi-axially, including the dimension of development. They should always keep in mind how developmental disorders lead to difficulties in everyday life, and treat developmental disorders in conjunction with adequate environmental modifications along with the treatment of other comorbid psychiatric disorders.

Grounding language in action and perception: from cognitive agents to humanoid robots.

PubMed

Cangelosi, Angelo

2010-06-01

In this review we concentrate on a grounded approach to the modeling of cognition through the methodologies of cognitive agents and developmental robotics. This work will focus on the modeling of the evolutionary and developmental acquisition of linguistic capabilities based on the principles of symbol grounding. We review cognitive agent and developmental robotics models of the grounding of language to demonstrate their consistency with the empirical and theoretical evidence on language grounding and embodiment, and to reveal the benefits of such an approach in the design of linguistic capabilities in cognitive robotic agents. In particular, three different models will be discussed, where the complexity of the agent's sensorimotor and cognitive system gradually increases: from a multi-agent simulation of language evolution, to a simulated robotic agent model for symbol grounding transfer, to a model of language comprehension in the humanoid robot iCub. The review also discusses the benefits of the use of humanoid robotic platform, and specifically of the open source iCub platform, for the study of embodied cognition. Copyright 2010 Elsevier B.V. All rights reserved.

Planar cell polarity pathway in vertebrate epidermal development, homeostasis and repair

PubMed Central

Dworkin, Sebastian; Jane, Stephen M

2011-01-01

The planar cell polarity (PCP) pathway plays a critical role in diverse developmental processes that require coordinated cellular movement, including neural tube closure and renal tubulogenesis. Recent studies have demonstrated that this pathway also has emerging relevance to the epidermis, as PCP signaling underpins many aspects of skin biology and pathology, including epidermal development, hair orientation, stem cell division and cancer. Coordinated cellular movement required for epidermal repair in mammals is also regulated by PCP signaling, and in this context, a new PCP gene encoding the developmental transcription factor Grainyhead-like 3 (Grhl3) is critical. This review focuses on the role that PCP signaling plays in the skin across a variety of epidermal functions and highlights perturbations that induce epidermal pathologies. PMID:22041517

Vascular Cells in Blood Vessel Wall Development and Disease.

PubMed

Mazurek, R; Dave, J M; Chandran, R R; Misra, A; Sheikh, A Q; Greif, D M

2017-01-01

The vessel wall is composed of distinct cellular layers, yet communication among individual cells within and between layers results in a dynamic and versatile structure. The morphogenesis of the normal vascular wall involves a highly regulated process of cell proliferation, migration, and differentiation. The use of modern developmental biological and genetic approaches has markedly enriched our understanding of the molecular and cellular mechanisms underlying these developmental events. Additionally, the application of similar approaches to study diverse vascular diseases has resulted in paradigm-shifting insights into pathogenesis. Further investigations into the biology of vascular cells in development and disease promise to have major ramifications on therapeutic strategies to combat pathologies of the vasculature. © 2017 Elsevier Inc. All rights reserved.

Adaptation of a software development methodology to the implementation of a large-scale data acquisition and control system. [for Deep Space Network

NASA Technical Reports Server (NTRS)

Madrid, G. A.; Westmoreland, P. T.

1983-01-01

A progress report is presented on a program to upgrade the existing NASA Deep Space Network in terms of a redesigned computer-controlled data acquisition system for channelling tracking, telemetry, and command data between a California-based control center and three signal processing centers in Australia, California, and Spain. The methodology for the improvements is oriented towards single subsystem development with consideration for a multi-system and multi-subsystem network of operational software. Details of the existing hardware configurations and data transmission links are provided. The program methodology includes data flow design, interface design and coordination, incremental capability availability, increased inter-subsystem developmental synthesis and testing, system and network level synthesis and testing, and system verification and validation. The software has been implemented thus far to a 65 percent completion level, and the methodology being used to effect the changes, which will permit enhanced tracking and communication with spacecraft, has been concluded to feature effective techniques.

TGF-beta: a new role for an old AktTOR.

PubMed

Goraksha-Hicks, Pankuri; Rathmell, Jeffrey C

2009-07-01

Nutrient overabundance is known to promote cellular hypertrophy, a significant pathological event in diseases like diabetes and cancer, although mechanisms have remained unclear. In this issue of Developmental Cell, Wu and Derynck provide a new model that links metabolism and cell growth by demonstrating that hyperglycemia can increase TGF-beta-dependent activation of the mTOR pathway to promote cellular hyperplasia.

Oxidative Stress, Unfolded Protein Response, and Apoptosis in Developmental Toxicity

PubMed Central

Kupsco, Allison; Schlenk, Daniel

2016-01-01

Physiological development requires precise spatiotemporal regulation of cellular and molecular processes. Disruption of these key events can generate developmental toxicity in the form of teratogenesis or mortality. The mechanism behind many developmental toxicants remains unknown. While recent work has focused on the unfolded protein response (UPR), oxidative stress, and apoptosis in the pathogenesis of disease, few studies have addressed their relationship in developmental toxicity. Redox regulation, UPR, and apoptosis are essential for physiological development and can be disturbed by a variety of endogenous and exogenous toxicants to generate lethality and diverse malformations. This review examines the current knowledge of the role of oxidative stress, UPR, and apoptosis in physiological development as well as in developmental toxicity, focusing on studies and advances in vertebrates model systems. PMID:26008783

Developmental pathways of childhood dark traits.

PubMed

De Clercq, Barbara; Hofmans, Joeri; Vergauwe, Jasmine; De Fruyt, Filip; Sharp, Carla

2017-10-01

The dark triad of personality has traditionally been defined by 3 interrelated constructs, defined as Narcissism, Machiavellianism, and Psychopathy. Although the content of each of these constructs is clearly represented in childhood maladaptive trait measures, no studies have jointly addressed the prospective developmental course of this core set of maladaptive characteristics throughout childhood and adolescence. The current study uses latent growth modeling to explore how early dark traits develop over time, relying on a selected set of 6 childhood maladaptive traits that conceptually cover the adult dark triad. Across a 5-wave multi-informant design spanning 10 years of childhood, adolescence, and emerging adulthood (Nwave 1 = 717, 54.4% girls, age range T1 = 8-14.7 years, mean age = 10.73), results indicate that childhood dark traits show to some extent shared growth across time, although notable unique growth variance was also observed. Early dark traits further demonstrate significant association patterns with an adult dark triad measure across informants and are increasingly able to discriminate among more and less prototypical profiles of adult dark triad scores. Findings are discussed from a developmental psychopathology framework, underscoring that the proposed set of childhood dark traits represents a meaningful developmental precursor of the adult dark triad. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

ZEBRAFISH AS AN IN VIVO MODEL FOR SUSTAINABLE CHEMICAL DESIGN.

PubMed

Noyes, Pamela D; Garcia, Gloria R; Tanguay, Robert L

2016-12-21

Heightened public awareness about the many thousands of chemicals in use and present as persistent contaminants in the environment has increased the demand for safer chemicals and more rigorous toxicity testing. There is a growing recognition that the use of traditional test models and empirical approaches is impractical for screening for toxicity the many thousands of chemicals in the environment and the hundreds of new chemistries introduced each year. These realities coupled with the green chemistry movement have prompted efforts to implement more predictive-based approaches to evaluate chemical toxicity early in product development. While used for many years in environmental toxicology and biomedicine, zebrafish use has accelerated more recently in genetic toxicology, high throughput screening (HTS), and behavioral testing. This review describes major advances in these testing methods that have positioned the zebrafish as a highly applicable model in chemical safety evaluations and sustainable chemistry efforts. Many toxic responses have been shown to be shared among fish and mammals owing to their generally well-conserved development, cellular networks, and organ systems. These shared responses have been observed for chemicals that impair endocrine functioning, development, and reproduction, as well as those that elicit cardiotoxicity and carcinogenicity, among other diseases. HTS technologies with zebrafish enable screening large chemical libraries for bioactivity that provide opportunities for testing early in product development. A compelling attribute of the zebrafish centers on being able to characterize toxicity mechanisms across multiple levels of biological organization from the genome to receptor interactions and cellular processes leading to phenotypic changes such as developmental malformations. Finally, there is a growing recognition of the links between human and wildlife health and the need for approaches that allow for assessment of real world multi-chemical exposures. The zebrafish is poised to be an important model in bridging these two conventionally separate areas of toxicology and characterizing the biological effects of chemical mixtures that could augment its role in sustainable chemistry.

ZEBRAFISH AS AN IN VIVO MODEL FOR SUSTAINABLE CHEMICAL DESIGN

PubMed Central

Noyes, Pamela D.; Garcia, Gloria R.; Tanguay, Robert L.

2016-01-01

Heightened public awareness about the many thousands of chemicals in use and present as persistent contaminants in the environment has increased the demand for safer chemicals and more rigorous toxicity testing. There is a growing recognition that the use of traditional test models and empirical approaches is impractical for screening for toxicity the many thousands of chemicals in the environment and the hundreds of new chemistries introduced each year. These realities coupled with the green chemistry movement have prompted efforts to implement more predictive-based approaches to evaluate chemical toxicity early in product development. While used for many years in environmental toxicology and biomedicine, zebrafish use has accelerated more recently in genetic toxicology, high throughput screening (HTS), and behavioral testing. This review describes major advances in these testing methods that have positioned the zebrafish as a highly applicable model in chemical safety evaluations and sustainable chemistry efforts. Many toxic responses have been shown to be shared among fish and mammals owing to their generally well-conserved development, cellular networks, and organ systems. These shared responses have been observed for chemicals that impair endocrine functioning, development, and reproduction, as well as those that elicit cardiotoxicity and carcinogenicity, among other diseases. HTS technologies with zebrafish enable screening large chemical libraries for bioactivity that provide opportunities for testing early in product development. A compelling attribute of the zebrafish centers on being able to characterize toxicity mechanisms across multiple levels of biological organization from the genome to receptor interactions and cellular processes leading to phenotypic changes such as developmental malformations. Finally, there is a growing recognition of the links between human and wildlife health and the need for approaches that allow for assessment of real world multi-chemical exposures. The zebrafish is poised to be an important model in bridging these two conventionally separate areas of toxicology and characterizing the biological effects of chemical mixtures that could augment its role in sustainable chemistry. PMID:28461781

Rational Design of Semiconductor Nanostructures for Functional Subcellular Interfaces.

PubMed

Parameswaran, Ramya; Tian, Bozhi

2018-05-15

One of the fundamental questions guiding research in the biological sciences is how cellular systems process complex physical and environmental cues and communicate with each other across multiple length scales. Importantly, aberrant signal processing in these systems can lead to diseases that can have devastating impacts on human lives. Biophysical studies in the past several decades have demonstrated that cells can respond to not only biochemical cues but also mechanical and electrical ones. Thus, the development of new materials that can both sense and modulate all of these pathways is necessary. Semiconducting nanostructures are an emerging class of discovery platforms and tools that can push the limits of our ability to modulate and sense biological behaviors for both fundamental research and clinical applications. These materials are of particular interest for interfacing with cellular systems due to their matched dimension with subcellular components (e.g., cytoskeletal filaments), and easily tunable properties in the electrical, optical and mechanical regimes. Rational design via traditional or new approaches, such as nanocasting and mesoscale chemical lithography, can allow us to control micro- and nanoscale features in nanowires to achieve new biointerfaces. Both processes endogenous to the target cell and properties of the material surface dictate the character of these interfaces. In this Account, we focus on (1) approaches for the rational design of semiconducting nanowires that exhibit unique structures for biointerfaces, (2) recent fundamental discoveries that yield robust biointerfaces at the subcellular level, (3) intracellular electrical and mechanical sensing, and (4) modulation of cellular behaviors through material topography and remote physical stimuli. In the first section, we discuss new approaches for the synthetic control of micro- and nanoscale features of these materials. In the second section, we focus on achieving biointerfaces with these rationally designed materials either intra- or extracellularly. We last delve into the use of these materials in sensing mechanical forces and electrical signals in various cellular systems as well as in instructing cellular behaviors. Future research in this area may shift the paradigm in fundamental biophysical research and biomedical applications through (1) the design and synthesis of new semiconductor-based materials and devices that interact specifically with targeted cells, (2) the clarification of many developmental, physiological, and anatomical aspects of cellular communications, (3) an understanding of how signaling between cells regulates synaptic development (e.g., information like this would offer new insight into how the nervous system works and provide new targets for the treatment of neurological diseases), (4) and the creation of new cellular materials that have the potential to open up completely new areas of application, such as in hybrid information processing systems.

Real time quantitative phase microscopy based on single-shot transport of intensity equation (ssTIE) method

NASA Astrophysics Data System (ADS)

Yu, Wei; Tian, Xiaolin; He, Xiaoliang; Song, Xiaojun; Xue, Liang; Liu, Cheng; Wang, Shouyu

2016-08-01

Microscopy based on transport of intensity equation provides quantitative phase distributions which opens another perspective for cellular observations. However, it requires multi-focal image capturing while mechanical and electrical scanning limits its real time capacity in sample detections. Here, in order to break through this restriction, real time quantitative phase microscopy based on single-shot transport of the intensity equation method is proposed. A programmed phase mask is designed to realize simultaneous multi-focal image recording without any scanning; thus, phase distributions can be quantitatively retrieved in real time. It is believed the proposed method can be potentially applied in various biological and medical applications, especially for live cell imaging.

Open-source do-it-yourself multi-color fluorescence smartphone microscopy

PubMed Central

Sung, Yulung; Campa, Fernando; Shih, Wei-Chuan

2017-01-01

Fluorescence microscopy is an important technique for cellular and microbiological investigations. Translating this technique onto a smartphone can enable particularly powerful applications such as on-site analysis, on-demand monitoring, and point-of-care diagnostics. Current fluorescence smartphone microscope setups require precise illumination and imaging alignment which altogether limit its broad adoption. We report a multi-color fluorescence smartphone microscope with a single contact lens-like add-on lens and slide-launched total-internal-reflection guided illumination for three common tasks in investigative fluorescence microscopy: autofluorescence, fluorescent stains, and immunofluorescence. The open-source, simple and cost-effective design has the potential for do-it-yourself fluorescence smartphone microscopy. PMID:29188104

Creating single-copy genetic circuits

PubMed Central

Lee, Jeong Wook; Gyorgy, Andras; Cameron, D. Ewen; Pyenson, Nora; Choi, Kyeong Rok; Way, Jeffrey C.; Silver, Pamela A.; Del Vecchio, Domitilla; Collins, James J.

2017-01-01

SUMMARY Synthetic biology is increasingly used to develop sophisticated living devices for basic and applied research. Many of these genetic devices are engineered using multi-copy plasmids, but as the field progresses from proof-of-principle demonstrations to practical applications, it is important to develop single-copy synthetic modules that minimize consumption of cellular resources and can be stably maintained as genomic integrants. Here we use empirical design, mathematical modeling and iterative construction and testing to build single-copy, bistable toggle switches with improved performance and reduced metabolic load that can be stably integrated into the host genome. Deterministic and stochastic models led us to focus on basal transcription to optimize circuit performance and helped to explain the resulting circuit robustness across a large range of component expression levels. The design parameters developed here provide important guidance for future efforts to convert functional multi-copy gene circuits into optimized single-copy circuits for practical, real-world use. PMID:27425413

Synthesis and evaluation of multi-wall carbon nanotube-paclitaxel complex as an anti-cancer agent.

PubMed

Ghasemvand, Fariba; Biazar, Esmaeil; Tavakolifard, Sara; Khaledian, Mohammad; Rahmanzadeh, Saeid; Momenzadeh, Daruosh; Afroosheh, Roshanak; Zarkalami, Faezeh; Shabannezhad, Marjan; Hesami Tackallou, Saeed; Massoudi, Nilofar; Heidari Keshel, Saeed

2016-01-01

The aim of this study was to design multi-walled carbon nanotubes (MWCNTs) loaded with paclitaxel (PTX) anti-cancer drug and investigate its anti-cancerous efficacy of human gastric cancer. Carbon nanotubes (CNTs) represent a novel nano-materials applied in various fields such as drug delivery due to their unique chemical properties and high drug loading. In this study, multi-walled carbon nanotubes (MWCNTs) pre-functionalized covalently with a paclitaxel (PTX) as an anti-cancer drug and evaluated by different analyses including, scanning electron microscope (SEM), particle size analyzer and cellular analyses. A well conjugated of anti-cancer drug on the carbon nanotube surfaces was shown. This study demonstrates that the MWCN-PTX complex is a potentially useful system for delivery of anti-cancer drugs. The flow cytometry, CFU and MTT assay results have disclosed that MWCNT/PTXs might promote apoptosis in MKN-45 gastric adenocarcinoma cell line. According to results, our simple method can be designed a candidate material for chemotherapy. It has presented a few bio-related applications including, their successful use as a nano-carriers for drug transport.

Transcriptome Dynamics during Maize Endosperm Development

PubMed Central

Feng, Jiaojiao; Xu, Shutu; Wang, Lei; Li, Feifei; Li, Yibo; Zhang, Renhe; Zhang, Xinghua; Xue, Jiquan; Guo, Dongwei

2016-01-01

The endosperm is a major organ of the seed that plays vital roles in determining seed weight and quality. However, genome-wide transcriptome patterns throughout maize endosperm development have not been comprehensively investigated to date. Accordingly, we performed a high-throughput RNA sequencing (RNA-seq) analysis of the maize endosperm transcriptome at 5, 10, 15 and 20 days after pollination (DAP). We found that more than 11,000 protein-coding genes underwent alternative splicing (AS) events during the four developmental stages studied. These genes were mainly involved in intracellular protein transport, signal transmission, cellular carbohydrate metabolism, cellular lipid metabolism, lipid biosynthesis, protein modification, histone modification, cellular amino acid metabolism, and DNA repair. Additionally, 7,633 genes, including 473 transcription factors (TFs), were differentially expressed among the four developmental stages. The differentially expressed TFs were from 50 families, including the bZIP, WRKY, GeBP and ARF families. Further analysis of the stage-specific TFs showed that binding, nucleus and ligand-dependent nuclear receptor activities might be important at 5 DAP, that immune responses, signalling, binding and lumen development are involved at 10 DAP, that protein metabolic processes and the cytoplasm might be important at 15 DAP, and that the responses to various stimuli are different at 20 DAP compared with the other developmental stages. This RNA-seq analysis provides novel, comprehensive insights into the transcriptome dynamics during early endosperm development in maize. PMID:27695101

The fetal programming of telomere biology hypothesis: an update

PubMed Central

Entringer, Sonja; Buss, Claudia; Wadhwa, Pathik D.

2018-01-01

Research on mechanisms underlying fetal programming of health and disease risk has focused primarily on processes that are specific to cell types, organs or phenotypes of interest. However, the observation that developmental conditions concomitantly influence a diverse set of phenotypes, the majority of which are implicated in age-related disorders, raises the possibility that such developmental conditions may additionally exert effects via a common underlying mechanism that involves cellular/molecular ageing–related processes. In this context, we submit that telomere biology represents a process of particular interest in humans because, firstly, this system represents among the most salient antecedent cellular phenotypes for common age-related disorders; secondly, its initial (newborn) setting appears to be particularly important for its long-term effects; and thirdly, its initial setting appears to be plastic and under developmental regulation. We propose that the effects of suboptimal intrauterine conditions on the initial setting of telomere length and telomerase expression/activity capacity may be mediated by the programming actions of stress-related maternal–placental–fetal oxidative, immune, endocrine and metabolic pathways in a manner that may ultimately accelerate cellular dysfunction, ageing and disease susceptibility over the lifespan. This perspectives paper provides an overview of each of the elements underlying this hypothesis, with an emphasis on recent developments, findings and future directions. This article is part of the theme issue ‘Understanding diversity in telomere dynamics’. PMID:29335381

The fetal programming of telomere biology hypothesis: an update.

PubMed

Entringer, Sonja; de Punder, Karin; Buss, Claudia; Wadhwa, Pathik D

2018-03-05

Research on mechanisms underlying fetal programming of health and disease risk has focused primarily on processes that are specific to cell types, organs or phenotypes of interest. However, the observation that developmental conditions concomitantly influence a diverse set of phenotypes, the majority of which are implicated in age-related disorders, raises the possibility that such developmental conditions may additionally exert effects via a common underlying mechanism that involves cellular/molecular ageing-related processes. In this context, we submit that telomere biology represents a process of particular interest in humans because, firstly, this system represents among the most salient antecedent cellular phenotypes for common age-related disorders; secondly, its initial (newborn) setting appears to be particularly important for its long-term effects; and thirdly, its initial setting appears to be plastic and under developmental regulation. We propose that the effects of suboptimal intrauterine conditions on the initial setting of telomere length and telomerase expression/activity capacity may be mediated by the programming actions of stress-related maternal-placental-fetal oxidative, immune, endocrine and metabolic pathways in a manner that may ultimately accelerate cellular dysfunction, ageing and disease susceptibility over the lifespan. This perspectives paper provides an overview of each of the elements underlying this hypothesis, with an emphasis on recent developments, findings and future directions.This article is part of the theme issue 'Understanding diversity in telomere dynamics'. © 2018 The Author(s).

Measuring Developmental Students' Mathematics Anxiety

ERIC Educational Resources Information Center

Ding, Yanqing

2016-01-01

This study conducted an item-level analysis of mathematics anxiety and examined the dimensionality of mathematics anxiety in a sample of developmental mathematics students (N = 162) by Multi-dimensional Random Coefficients Multinominal Logit Model (MRCMLM). The results indicate a moderately correlated factor structure of mathematics anxiety (r =…

Improved antimicrobial therapy with cationic tetra- and octa-substituted phthalocyanines

NASA Astrophysics Data System (ADS)

Angelov, I.; Mantareva, V.; Kussovski, V.; Woehrle, D.; Borisova, E.; Avramov, L.

2008-12-01

Photodynamic therapy (PDT) today is an innovative and not yet widespread light-drug initiated treatment that is based on the photoactive compound irradiated with proper light to produce oxygen species that are toxic to the pathogenic biological objects- bacteria, viruses, tumor cells. The obstacles that limited the efficacy of PDT concern to the selectivity and multi-drug resistance prolong time for cellular release and side effects of skin photosensitivity for commercial porphyrin originated photosensitizers (PS). Now there are very intensive investigations for introducing in practice a new, with a least side effects PSs for PDT. The usefulness of the more extended macromolecules structured with proper substituents refers not only to the improved optical properties like far-red and with intensive absorption and emission capacity, but mainly to the ability for selective delivery and adhesion to the target cells, such as bacteria or other pathogens. The present study focuses on the charge effect of photodynamic agent on the uptake capacity toward gram-negative bacteria cells and their further photoinactivation. The multi-drug resistant microorganism Aeromanas hydrophilla, which is causing diseases to fishes and humans, is treated. The new octa-cationic phthalocyanines are designed to compare PDT efficacy to the efficacy of tetra-substituted derivatives with the same functional peripheral substituents. The higher cellular accumulation to the bacteria cells as a result of the high number of positive charges of photosensitizer, leading to the better adhesion to the cellular membranes and improved photoinactivation of bacteria causing superficial and intraorgan infections. These results set a base of a rationale design of covalently octa-substituted phthalocyanines with positive charge for a successful treatment of microorganisms.

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

PubMed

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

2010-10-01

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

Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally.

PubMed

Barrett, Catherine E; Hennessey, Thomas M; Gordon, Katelyn M; Ryan, Steve J; McNair, Morgan L; Ressler, Kerry J; Rainnie, Donald G

2017-01-01

The amygdala controls socioemotional behavior and has consistently been implicated in the etiology of autism spectrum disorder (ASD). Precocious amygdala development is commonly reported in ASD youth with the degree of overgrowth positively correlated to the severity of ASD symptoms. Prenatal exposure to VPA leads to an ASD phenotype in both humans and rats and has become a commonly used tool to model the complexity of ASD symptoms in the laboratory. Here, we examined abnormalities in gene expression in the amygdala and socioemotional behavior across development in the valproic acid (VPA) rat model of ASD. Rat dams received oral gavage of VPA (500 mg/kg) or saline daily between E11 and 13. Socioemotional behavior was tracked across development in both sexes. RNA sequencing and proteomics were performed on amygdala samples from male rats across development. Effects of VPA on time spent in social proximity and anxiety-like behavior were sex dependent, with social abnormalities presenting in males and heightened anxiety in females. Across time VPA stunted developmental and immune, but enhanced cellular death and disorder, pathways in the amygdala relative to saline controls. At postnatal day 10, gene pathways involved in nervous system and cellular development displayed predicted activations in prenatally exposed VPA amygdala samples. By juvenile age, however, transcriptomic and proteomic pathways displayed reductions in cellular growth and neural development. Alterations in immune pathways, calcium signaling, Rho GTPases, and protein kinase A signaling were also observed. As behavioral, developmental, and genomic alterations are similar to those reported in ASD, these results lend support to prenatal exposure to VPA as a useful tool for understanding how developmental insults to molecular pathways in the amygdala give rise to ASD-related syndromes.

Travelling waves in somitogenesis: Collective cellular properties emerge from time-delayed juxtacrine oscillation coupling.

PubMed

Tomka, Tomas; Iber, Dagmar; Boareto, Marcelo

2018-04-24

The sculpturing of the vertebrate body plan into segments begins with the sequential formation of somites in the presomitic mesoderm (PSM). The rhythmicity of this process is controlled by travelling waves of gene expression. These kinetic waves emerge from coupled cellular oscillators and sweep across the PSM. In zebrafish, the oscillations are driven by autorepression of her genes and are synchronized via Notch signalling. Mathematical modelling has played an important role in explaining how collective properties emerge from the molecular interactions. Increasingly more quantitative experimental data permits the validation of those mathematical models, yet leads to increasingly more complex model formulations that hamper an intuitive understanding of the underlying mechanisms. Here, we review previous efforts, and design a mechanistic model of the her1 oscillator, which represents the experimentally viable her7;hes6 double mutant. This genetically simplified system is ideally suited to conceptually recapitulate oscillatory entrainment and travelling wave formation, and to highlight open questions. It shows that three key parameters, the autorepression delay, the juxtacrine coupling delay, and the coupling strength, are sufficient to understand the emergence of the collective period, the collective amplitude, and the synchronization of neighbouring Her1 oscillators. Moreover, two spatiotemporal time delay gradients, in the autorepression and in the juxtacrine signalling, are required to explain the collective oscillatory dynamics and synchrony of PSM cells. The highlighted developmental principles likely apply more generally to other developmental processes, including neurogenesis and angiogenesis. Copyright © 2018. Published by Elsevier Ltd.

Leading multi-professional teams in the children's workforce: an action research project.

PubMed

Stuart, Kaz

2012-01-01

The 2004 Children Act in the UK saw the introduction of integrated working in children's services. A raft of change followed with processes designed to make joint working easier, and models and theories to support the development of integrated work. This paper explores the links between key concepts and practice. A practitioner action research approach is taken using an autoethnographic account kept over six months. The research question was, to what extent is this group collaborating? When the architecture of practice was revealed, differences between espoused and real practice could be seen. Whilst understanding and displaying the outward signs of an effective multi professional group, the individuals did not trust one another. This was exhibited by covert interprofessional issues. As a result, collaborative inertia was achieved. This realisation prompted them to participate in further developmental and participative action research. The paper concludes that trust and relational agency are central to effective leadership of multi professional teams.

Leading multi-professional teams in the children’s workforce: an action research project

PubMed Central

Stuart, Kaz

2012-01-01

Introduction The 2004 Children Act in the UK saw the introduction of integrated working in children’s services. A raft of change followed with processes designed to make joint working easier, and models and theories to support the development of integrated work. This paper explores the links between key concepts and practice. Methods A practitioner action research approach is taken using an autoethnographic account kept over six months. The research question was, to what extent is this group collaborating? Results When the architecture of practice was revealed, differences between espoused and real practice could be seen. Whilst understanding and displaying the outward signs of an effective multi professional group, the individuals did not trust one another. This was exhibited by covert interprofessional issues. As a result, collaborative inertia was achieved. This realisation prompted them to participate in further developmental and participative action research. Conclusion The paper concludes that trust and relational agency are central to effective leadership of multi professional teams. PMID:22371690

The Multiple Faces of Interparental Conflict: Implications for Cascades of Children’s Insecurity and Externalizing Problems

PubMed Central

Davies, Patrick T.; Hentges, Rochelle F.; Coe, Jesse L.; Martin, Meredith J.; Sturge-Apple, Melissa L.; Cummings, E. Mark

2016-01-01

This multi-study paper examined the relative strength of mediational pathways involving hostile, disengaged, and uncooperative forms of interparental conflict, children’s emotional insecurity, and their externalizing problems across two longitudinal studies. Participants in Study 1 consisted of 243 preschool children (M age = 4.60 years) and their parents, whereas Study 2 consisted of 263 adolescents (M age = 12.62 years) and their parents. Both studies utilized multi-method, multi-informant assessment batteries within a longitudinal design with three measurement occasions. Across both studies, lagged, autoregressive tests of the mediational paths revealed that interparental hostility was a significantly stronger predictor of the prospective cascade of children’s insecurity and externalizing problems than interparental disengagement and low levels of interparental cooperation. Findings further indicated that interparental disengagement was a stronger predictor of the insecurity pathway than was low interparental cooperation for the sample of adolescents in Study 2. Results are discussed in relation to how they inform and advance developmental models of family risk. PMID:27175983

Multi-ampoule Bridgman growth of halide scintillator crystals using the self-seeding method

NASA Astrophysics Data System (ADS)

Lindsey, Adam C.; Wu, Yuntao; Zhuravleva, Mariya; Loyd, Matthew; Koschan, Merry; Melcher, Charles L.

2017-07-01

We investigate the multi-ampoule growth at 25 mm diameter of ternary iodide single crystal scintillator KCaI3:Eu using the randomly oriented self-seeded Bridgman method. We compare scintillation performance between cubic inch scale crystals containing small variations of low nominal europium concentrations previously shown to balance light yield with self-absorption in the host crystal. Growth conditions were optimized in the developmental furnace and four 2 in3 KCaI3:Eu crystals were grown simultaneously producing a total of six 25 mm × 25 mm cylinders. Small variations in activator concentration did not result in significant performance differences among the six measured crystals. A range of energy resolutions of 3.5-4.7% at 662 keV was achieved, surpassing that of NaI:Tl crystals commonly used in spectroscopic detection applications. The function and basic design of the multi-ampoule furnace as well as the process of growing single crystals of KCaI3 is included here.

Metamorphosis in solitary ascidians.

PubMed

Karaiskou, Anthi; Swalla, Billie J; Sasakura, Yasunori; Chambon, Jean-Philippe

2015-01-01

Embryonic and postembryonic development in ascidians have been studied for over a century, but it is only in the last 10 years that the complex molecular network involved in coordinating postlarval development and metamorphosis has started to emerge. In most ascidians, the transition from the larval to the sessile juvenile/adult stage, or metamorphosis, requires a combination of environmental and endogenous signals and is characterized by coordinated global morphogenetic changes that are initiated by the adhesion of the larvae. Cloney was the first to describe cellular events of ascidians' metamorphosis in 1978 and only recently elements of the molecular regulation of this crucial developmental step have been revealed. This review aims to present a thorough view of this crucial developmental step by combining recent molecular data to the already established cellular events. © 2014 Wiley Periodicals, Inc.

Neuromodulation of hypoglossal motoneurons: cellular and developmental mechanisms.

PubMed

Bayliss, D A; Viana, F; Talley, E M; Berger, A J

1997-11-01

Hypoglossal motoneurons (HMs) in the caudal brainstem have a respiratory-related activity pattern and contribute to control of upper airway resistance. In this review, we focus primarily on signalling mechanisms utilized by neurotransmitters to enhance HM excitability. In particular, we consider: (1) the membrane depolarization induced by a number of different putative transmitters [thyrotropin-releasing hormone (TRH), serotonin (5-HT), norepinephrine (NE)]; and (2) the inhibition of a calcium-dependent spike after hyperpolarization (AHP) by 5-HT and its effect on firing behavior. Potential functional consequences on HM behavior of these different neurotransmitter effects is discussed. In addition, we describe postnatal changes in transmitter effects and suggest potential cellular mechanisms to explain those developmental changes. Most of the data discussed are derived from in vitro electrophysiological recordings performed in preparations from neonatal and adult rats.

In vitro acute and developmental neurotoxicity screening: an overview of cellular platforms and high-throughput technical possibilities.

PubMed

Schmidt, Béla Z; Lehmann, Martin; Gutbier, Simon; Nembo, Erastus; Noel, Sabrina; Smirnova, Lena; Forsby, Anna; Hescheler, Jürgen; Avci, Hasan X; Hartung, Thomas; Leist, Marcel; Kobolák, Julianna; Dinnyés, András

2017-01-01

Neurotoxicity and developmental neurotoxicity are important issues of chemical hazard assessment. Since the interpretation of animal data and their extrapolation to man is challenging, and the amount of substances with information gaps exceeds present animal testing capacities, there is a big demand for in vitro tests to provide initial information and to prioritize for further evaluation. During the last decade, many in vitro tests emerged. These are based on animal cells, human tumour cell lines, primary cells, immortalized cell lines, embryonic stem cells, or induced pluripotent stem cells. They differ in their read-outs and range from simple viability assays to complex functional endpoints such as neural crest cell migration. Monitoring of toxicological effects on differentiation often requires multiomics approaches, while the acute disturbance of neuronal functions may be analysed by assessing electrophysiological features. Extrapolation from in vitro data to humans requires a deep understanding of the test system biology, of the endpoints used, and of the applicability domains of the tests. Moreover, it is important that these be combined in the right way to assess toxicity. Therefore, knowledge on the advantages and disadvantages of all cellular platforms, endpoints, and analytical methods is essential when establishing in vitro test systems for different aspects of neurotoxicity. The elements of a test, and their evaluation, are discussed here in the context of comprehensive prediction of potential hazardous effects of a compound. We summarize the main cellular characteristics underlying neurotoxicity, present an overview of cellular platforms and read-out combinations assessing distinct parts of acute and developmental neurotoxicology, and highlight especially the use of stem cell-based test systems to close gaps in the available battery of tests.

Design of small confocal endo-microscopic probe working under multiwavelength environment

NASA Astrophysics Data System (ADS)

Kim, Young-Duk; Ahn, MyoungKi; Gweon, Dae-Gab

2010-02-01

Recently, optical imaging system is widely used in medical purpose. By using optical imaging system specific diseases can be easily diagnosed at early stage because optical imaging system has high resolution performance and various imaging method. These methods are used to get high resolution image of human body and can be used to verify whether the cell is infected by virus. Confocal microscope is one of the famous imaging systems which is used for in-vivo imaging. Because most of diseases are accompanied with cellular level changes, doctors can diagnosis at early stage by observing the cellular image of human organ. Current research is focused in the development of endo-microscope that has great advantage in accessibility to human body. In this research, I designed small probe that is connected to confocal microscope through optical fiber bundle and work as endo-microscope. And this small probe is mainly designed to correct chromatic aberration to use various laser sources for both fluorescence type and reflection type confocal images. By using two kinds of laser sources at the same time we demonstrated multi-modality confocal endo-microscope.

Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast

PubMed Central

Dephoure, Noah; Hwang, Sunyoung; O'Sullivan, Ciara; Dodgson, Stacie E; Gygi, Steven P; Amon, Angelika; Torres, Eduardo M

2014-01-01

Aneuploidy causes severe developmental defects and is a near universal feature of tumor cells. Despite its profound effects, the cellular processes affected by aneuploidy are not well characterized. Here, we examined the consequences of aneuploidy on the proteome of aneuploid budding yeast strains. We show that although protein levels largely scale with gene copy number, subunits of multi-protein complexes are notable exceptions. Posttranslational mechanisms attenuate their expression when their encoding genes are in excess. Our proteomic analyses further revealed a novel aneuploidy-associated protein expression signature characteristic of altered metabolism and redox homeostasis. Indeed aneuploid cells harbor increased levels of reactive oxygen species (ROS). Interestingly, increased protein turnover attenuates ROS levels and this novel aneuploidy-associated signature and improves the fitness of most aneuploid strains. Our results show that aneuploidy causes alterations in metabolism and redox homeostasis. Cells respond to these alterations through both transcriptional and posttranscriptional mechanisms. DOI: http://dx.doi.org/10.7554/eLife.03023.001 PMID:25073701

A small molecule-based strategy for endothelial differentiation and three-dimensional morphogenesis from human embryonic stem cells.

PubMed

Geng, Yijie; Feng, Bradley

2016-07-01

The emerging models of human embryonic stem cell (hESC) self-organizing organoids provide a valuable in vitro platform for studying self-organizing processes that presumably mimic in vivo human developmental events. Here we report that through a chemical screen, we identified two novel and structurally similar small molecules BIR1 and BIR2 which robustly induced the self-organization of a balloon-shaped three-dimensional structure when applied to two-dimensional adherent hESC cultures in the absence of growth factors. Gene expression analyses and functional assays demonstrated an endothelial identity of this balloon-like structure, while cell surface marker analyses revealed a VE-cadherin(+)CD31(+)CD34(+)KDR(+)CD43(-) putative endothelial progenitor population. Furthermore, molecular marker labeling and morphological examinations characterized several other distinct DiI-Ac-LDL(+) multi-cellular modules and a VEGFR3(+) sprouting structure in the balloon cultures that likely represented intermediate structures of balloon-formation.

Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration

PubMed Central

Wan, Jijun; Yourshaw, Michael; Mamsa, Hafsa; Rudnik-Schöneborn, Sabine; Menezes, Manoj P.; Hong, Ji Eun; Leong, Derek W.; Senderek, Jan; Salman, Michael S.; Chitayat, David; Seeman, Pavel; von Moers, Arpad; Graul-Neumann, Luitgard; Kornberg, Andrew J.; Castro-Gago, Manuel; Sobrido, María-Jesús; Sanefuji, Masafumi; Shieh, Perry B.; Salamon, Noriko; Kim, Ronald C.; Vinters, Harry V.; Chen, Zugen; Zerres, Klaus; Ryan, Monique M.; Nelson, Stanley F.; Jen, Joanna C.

2012-01-01

RNA exosomes are multi-subunit complexes conserved throughout evolution1 and emerging as the major cellular machinery for processing, surveillance, and turnover of a diverse spectrum of coding and non-coding RNA substrates essential for viability2. By exome sequencing, we discovered recessive mutations in exosome component 3 (EXOSC3) in four siblings with infantile spinal motor neuron disease, cerebellar atrophy, progressive microcephaly, and profound global developmental delay, consistent with pontocerebellar hypoplasia type 1 [PCH1; OMIM 607596]3–6. We identified mutations in EXOSC3 in an additional 8 of 12 families with PCH1. Morpholino knockdown of exosc3 in zebrafish embryos caused embryonic maldevelopment with small brain and poor motility, reminiscent of human clinical features and largely rescued by coinjected wildtype but not mutant exosc3 mRNA. These findings represent the first example of an RNA exosome gene responsible for a human disease and further implicate dysregulation of RNA processing in cerebellar and spinal motor neuron maldevelopment and degeneration. PMID:22544365

Cellular and Pectin Dynamics during Abscission Zone Development and Ripe Fruit Abscission of the Monocot Oil Palm

PubMed Central

Roongsattham, Peerapat; Morcillo, Fabienne; Fooyontphanich, Kim; Jantasuriyarat, Chatchawan; Tragoonrung, Somvong; Amblard, Philippe; Collin, Myriam; Mouille, Gregory; Verdeil, Jean-Luc; Tranbarger, Timothy J.

2016-01-01

The oil palm (Elaeis guineensis Jacq.) fruit primary abscission zone (AZ) is a multi-cell layered boundary region between the pedicel (P) and mesocarp (M) tissues. To examine the cellular processes that occur during the development and function of the AZ cell layers, we employed multiple histological and immunohistochemical methods combined with confocal, electron and Fourier-transform infrared (FT-IR) microspectroscopy approaches. During early fruit development and differentiation of the AZ, the orientation of cell divisions in the AZ was periclinal compared with anticlinal divisions in the P and M. AZ cell wall width increased earlier during development suggesting cell wall assembly occurred more rapidly in the AZ than the adjacent P and M tissues. The developing fruit AZ contain numerous intra-AZ cell layer plasmodesmata (PD), but very few inter-AZ cell layer PD. In the AZ of ripening fruit, PD were less frequent, wider, and mainly intra-AZ cell layer localized. Furthermore, DAPI staining revealed nuclei are located adjacent to PD and are remarkably aligned within AZ layer cells, and remain aligned and intact after cell separation. The polarized accumulation of ribosomes, rough endoplasmic reticulum, mitochondria, and vesicles suggested active secretion at the tip of AZ cells occurred during development which may contribute to the striated cell wall patterns in the AZ cell layers. AZ cells accumulated intracellular pectin during development, which appear to be released and/or degraded during cell separation. The signal for the JIM5 epitope, that recognizes low methylesterified and un-methylesterified homogalacturonan (HG), increased in the AZ layer cell walls prior to separation and dramatically increased on the separated AZ cell surfaces. Finally, FT-IR microspectroscopy analysis indicated a decrease in methylesterified HG occurred in AZ cell walls during separation, which may partially explain an increase in the JIM5 epitope signal. The results obtained through a multi-imaging approach allow an integrated view of the dynamic developmental processes that occur in a multi-layered boundary AZ and provide evidence for distinct regulatory mechanisms that underlie oil palm fruit AZ development and function. PMID:27200017

Self-Control and Emotional and Verbal Aggression in Dating Relationships: A Dyadic Understanding.

PubMed

Baker, Elizabeth A; Klipfel, Katherine M; van Dulmen, Manfred H M

2016-08-01

Guided by the dynamic developmental systems perspective, this study extends past research by examining the association between self-control and emotional and verbal aggression (EVA) using a dyadic multi-method design. Guided by empirical research and the dynamic developmental systems perspective, we hypothesized that (a) there would be a negative association between one's own self-control and one's own perpetration of EVA and (b) there would also be a negative association between one's partner's self-control and one's own perpetration of EVA. One hundred twenty heterosexual dating couples (ages 18-25 years) provided data on self-control (Grasmick et al.'s Low Self-Control Scale; reverse scored for ease of interpretation), self-reported perpetration of EVA (Emotional and Verbal Abuse subscale of the Conflict in Adolescent Dating Relationships Inventory), and observationally assessed perpetration of EVA. Data were analyzed using path analyses within the Actor-Partner Interdependence Model (APIM) framework. Consistent with previous findings, we found that self-control was negatively associated with the perpetration of EVA. Furthermore, we found partner effects, such that female-but not male-self-control predicted partner-observed perpetration of EVA. These findings highlight the importance of examining risk factors for EVA of both partners. Our findings also suggest that the association between self-control and EVA is partially a function of whether EVA is assessed through self-report or observational methodology. This highlights the need to conduct multi-method assessments in future research. As discussed in the article, our findings have implications for theories on intimate partner violence, study designs, and couple interventions.

In silico design of a DNA-based HIV-1 multi-epitope vaccine for Chinese populations

PubMed Central

Yang, Yi; Sun, Weilai; Guo, Jingjing; Zhao, Guangyu; Sun, Shihui; Yu, Hong; Guo, Yan; Li, Jungfeng; Jin, Xia; Du, Lanying; Jiang, Shibo; Kou, Zhihua; Zhou, Yusen

2015-01-01

The development of an HIV-1 vaccine that is capable of inducing effective and broadly cross-reactive humoral and cellular immune responses remains a challenging task because of the extensive diversity of HIV-1, the difference of virus subtypes (clades) in different geographical regions, and the polymorphism of human leukocyte antigens (HLA). We performed an in silico design of 3 DNA vaccines, designated pJW4303-MEG1, pJW4303-MEG2 and pJW4303-MEG3, encoding multi-epitopes that are highly conserved within the HIV-1 subtypes most prevalent in China and can be recognized through HLA alleles dominant in China. The pJW4303-MEG1-encoded protein consisted of one Th epitope in Env, and one, 2, and 6 epitopes in Pol, Env, and Gag proteins, respectively, with a GGGS linker sequence between epitopes. The pJW4303-MEG2-encoded protein contained similar epitopes in a different order, but with the same linker as pJW4303-MEG1. The pJW4303-MEG3-encoded protein contained the same epitopes in the same order as that of pJW4303-MEG2, but with a different linker sequence (AAY). To evaluate immunogenicity, mice were immunized intramuscularly with these DNA vaccines. Both pJW4303-MEG1 and pJW4303-MEG2 vaccines induced equally potent humoral and cellular immune responses in the vaccinated mice, while pJW4303-MEG3 did not induce immune responses. These results indicate that both epitope and linker sequences are important in designing effective epitope-based vaccines against HIV-1 and other viruses. PMID:25839222

Cross-Informant Agreement on Child and Adolescent Withdrawn Behavior: A Latent Class Approach

ERIC Educational Resources Information Center

Rubin, David H.; Althoff, Robert R.; Walkup, John T.; Hudziak, James J.

2013-01-01

Withdrawn behavior (WB) relates to many developmental outcomes, including pervasive developmental disorders, anxiety, depression, psychosis, personality disorders and suicide. No study has compared the latent profiles of different informants' reports on WB. This study uses multi-informant latent class analyses (LCA) of the child behavior checklist…

Visualizing Viral Protein Structures in Cells Using Genetic Probes for Correlated Light and Electron Microscopy

PubMed Central

Ou, Horng D.; Deerinck, Thomas J.; Bushong, Eric; Ellisman, Mark H.; O’Shea, Clodagh C.

2015-01-01

Structural studies of viral proteins most often use high-resolution techniques such as X-ray crystallography, nuclear magnetic resonance, single particle negative stain, or cryo-electron microscopy (EM) to reveal atomic interactions of soluble, homogeneous viral proteins or viral protein complexes. Once viral proteins or complexes are separated from their host’s cellular environment, their natural in-situ structure and details of how they interact with other cellular components may be lost. EM has been an invaluable tool in virology since its introduction in the late 1940’s and subsequent application to cells in the 1950’s. EM studies have expanded our knowledge of viral entry, viral replication, alteration of cellular components, and viral lysis. Most of these early studies were focused on conspicuous morphological cellular changes, because classic EM metal stains were designed to highlight classes of cellular structures rather than specific molecular structures. Much later, to identify viral proteins inducing specific structural configurations at the cellular level, immunostaining with a primary antibody followed by colloidal gold secondary antibody was employed to mark the location of specific viral proteins. This technique can suffer from artifacts in cellular ultrastructure due to compromises required to provide access to the immuno-reagents. Immunolocalization methods also require the generation of highly specific antibodies, which may not be available for every viral protein. Here we discuss new methods to visualize viral proteins and structures at high resolutions in-situ using correlated light and electron microscopy (CLEM). We discuss the use of genetically encoded protein fusions that oxidize diaminobenzidine (DAB) into an osmiophilic polymer that can be visualized by EM. Detailed protocols for applying the genetically encoded photo-oxidizing protein MiniSOG to a viral protein, photo-oxidation of the fusion protein to yield DAB polymer staining, and preparation of photo-oxidized samples for TEM and serial block-face scanning EM (SBEM) for large-scale volume EM data acquisition are also presented. As an example, we discuss the recent multi-scale analysis of Adenoviral protein E4-ORF3 that reveals a new type of multi-functional polymer that disrupts multiple cellular proteins. This new capability to visualize unambiguously specific viral protein structures at high resolutions in the native cellular environment is revealing new insights into how they usurp host proteins and functions to drive pathological viral replication. PMID:26066760

Visualizing viral protein structures in cells using genetic probes for correlated light and electron microscopy.

PubMed

Ou, Horng D; Deerinck, Thomas J; Bushong, Eric; Ellisman, Mark H; O'Shea, Clodagh C

2015-11-15

Structural studies of viral proteins most often use high-resolution techniques such as X-ray crystallography, nuclear magnetic resonance, single particle negative stain, or cryo-electron microscopy (EM) to reveal atomic interactions of soluble, homogeneous viral proteins or viral protein complexes. Once viral proteins or complexes are separated from their host's cellular environment, their natural in situ structure and details of how they interact with other cellular components may be lost. EM has been an invaluable tool in virology since its introduction in the late 1940's and subsequent application to cells in the 1950's. EM studies have expanded our knowledge of viral entry, viral replication, alteration of cellular components, and viral lysis. Most of these early studies were focused on conspicuous morphological cellular changes, because classic EM metal stains were designed to highlight classes of cellular structures rather than specific molecular structures. Much later, to identify viral proteins inducing specific structural configurations at the cellular level, immunostaining with a primary antibody followed by colloidal gold secondary antibody was employed to mark the location of specific viral proteins. This technique can suffer from artifacts in cellular ultrastructure due to compromises required to provide access to the immuno-reagents. Immunolocalization methods also require the generation of highly specific antibodies, which may not be available for every viral protein. Here we discuss new methods to visualize viral proteins and structures at high resolutions in situ using correlated light and electron microscopy (CLEM). We discuss the use of genetically encoded protein fusions that oxidize diaminobenzidine (DAB) into an osmiophilic polymer that can be visualized by EM. Detailed protocols for applying the genetically encoded photo-oxidizing protein MiniSOG to a viral protein, photo-oxidation of the fusion protein to yield DAB polymer staining, and preparation of photo-oxidized samples for TEM and serial block-face scanning EM (SBEM) for large-scale volume EM data acquisition are also presented. As an example, we discuss the recent multi-scale analysis of Adenoviral protein E4-ORF3 that reveals a new type of multi-functional polymer that disrupts multiple cellular proteins. This new capability to visualize unambiguously specific viral protein structures at high resolutions in the native cellular environment is revealing new insights into how they usurp host proteins and functions to drive pathological viral replication. Copyright © 2015 Elsevier Inc. All rights reserved.

Coupling biomechanics to a cellular level model: an approach to patient-specific image driven multi-scale and multi-physics tumor simulation.

PubMed

May, Christian P; Kolokotroni, Eleni; Stamatakos, Georgios S; Büchler, Philippe

2011-10-01

Modeling of tumor growth has been performed according to various approaches addressing different biocomplexity levels and spatiotemporal scales. Mathematical treatments range from partial differential equation based diffusion models to rule-based cellular level simulators, aiming at both improving our quantitative understanding of the underlying biological processes and, in the mid- and long term, constructing reliable multi-scale predictive platforms to support patient-individualized treatment planning and optimization. The aim of this paper is to establish a multi-scale and multi-physics approach to tumor modeling taking into account both the cellular and the macroscopic mechanical level. Therefore, an already developed biomodel of clinical tumor growth and response to treatment is self-consistently coupled with a biomechanical model. Results are presented for the free growth case of the imageable component of an initially point-like glioblastoma multiforme tumor. The composite model leads to significant tumor shape corrections that are achieved through the utilization of environmental pressure information and the application of biomechanical principles. Using the ratio of smallest to largest moment of inertia of the tumor material to quantify the effect of our coupled approach, we have found a tumor shape correction of 20% by coupling biomechanics to the cellular simulator as compared to a cellular simulation without preferred growth directions. We conclude that the integration of the two models provides additional morphological insight into realistic tumor growth behavior. Therefore, it might be used for the development of an advanced oncosimulator focusing on tumor types for which morphology plays an important role in surgical and/or radio-therapeutic treatment planning. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cell Motility Dynamics: A Novel Segmentation Algorithm to Quantify Multi-Cellular Bright Field Microscopy Images

PubMed Central

Zaritsky, Assaf; Natan, Sari; Horev, Judith; Hecht, Inbal; Wolf, Lior; Ben-Jacob, Eshel; Tsarfaty, Ilan

2011-01-01

Confocal microscopy analysis of fluorescence and morphology is becoming the standard tool in cell biology and molecular imaging. Accurate quantification algorithms are required to enhance the understanding of different biological phenomena. We present a novel approach based on image-segmentation of multi-cellular regions in bright field images demonstrating enhanced quantitative analyses and better understanding of cell motility. We present MultiCellSeg, a segmentation algorithm to separate between multi-cellular and background regions for bright field images, which is based on classification of local patches within an image: a cascade of Support Vector Machines (SVMs) is applied using basic image features. Post processing includes additional classification and graph-cut segmentation to reclassify erroneous regions and refine the segmentation. This approach leads to a parameter-free and robust algorithm. Comparison to an alternative algorithm on wound healing assay images demonstrates its superiority. The proposed approach was used to evaluate common cell migration models such as wound healing and scatter assay. It was applied to quantify the acceleration effect of Hepatocyte growth factor/scatter factor (HGF/SF) on healing rate in a time lapse confocal microscopy wound healing assay and demonstrated that the healing rate is linear in both treated and untreated cells, and that HGF/SF accelerates the healing rate by approximately two-fold. A novel fully automated, accurate, zero-parameters method to classify and score scatter-assay images was developed and demonstrated that multi-cellular texture is an excellent descriptor to measure HGF/SF-induced cell scattering. We show that exploitation of textural information from differential interference contrast (DIC) images on the multi-cellular level can prove beneficial for the analyses of wound healing and scatter assays. The proposed approach is generic and can be used alone or alongside traditional fluorescence single-cell processing to perform objective, accurate quantitative analyses for various biological applications. PMID:22096600

Cell motility dynamics: a novel segmentation algorithm to quantify multi-cellular bright field microscopy images.

PubMed

Zaritsky, Assaf; Natan, Sari; Horev, Judith; Hecht, Inbal; Wolf, Lior; Ben-Jacob, Eshel; Tsarfaty, Ilan

2011-01-01

Confocal microscopy analysis of fluorescence and morphology is becoming the standard tool in cell biology and molecular imaging. Accurate quantification algorithms are required to enhance the understanding of different biological phenomena. We present a novel approach based on image-segmentation of multi-cellular regions in bright field images demonstrating enhanced quantitative analyses and better understanding of cell motility. We present MultiCellSeg, a segmentation algorithm to separate between multi-cellular and background regions for bright field images, which is based on classification of local patches within an image: a cascade of Support Vector Machines (SVMs) is applied using basic image features. Post processing includes additional classification and graph-cut segmentation to reclassify erroneous regions and refine the segmentation. This approach leads to a parameter-free and robust algorithm. Comparison to an alternative algorithm on wound healing assay images demonstrates its superiority. The proposed approach was used to evaluate common cell migration models such as wound healing and scatter assay. It was applied to quantify the acceleration effect of Hepatocyte growth factor/scatter factor (HGF/SF) on healing rate in a time lapse confocal microscopy wound healing assay and demonstrated that the healing rate is linear in both treated and untreated cells, and that HGF/SF accelerates the healing rate by approximately two-fold. A novel fully automated, accurate, zero-parameters method to classify and score scatter-assay images was developed and demonstrated that multi-cellular texture is an excellent descriptor to measure HGF/SF-induced cell scattering. We show that exploitation of textural information from differential interference contrast (DIC) images on the multi-cellular level can prove beneficial for the analyses of wound healing and scatter assays. The proposed approach is generic and can be used alone or alongside traditional fluorescence single-cell processing to perform objective, accurate quantitative analyses for various biological applications.

Adaptive design lessons from professional architects

NASA Astrophysics Data System (ADS)

Geiger, Ray W.; Snell, J. T.

1993-09-01

Psychocybernetic systems engineering design conceptualization is mimicking the evolutionary path of habitable environmental design and the professional practice of building architecture, construction, and facilities management. In pursuing better ways to design cellular automata and qualification classifiers in a design process, we have found surprising success in exploring certain more esoteric approaches, e.g., the vision of interdisciplinary artistic discovery in and around creative problem solving. Our evaluation in research into vision and hybrid sensory systems associated with environmental design and human factors has led us to discover very specific connections between the human spirit and quality design. We would like to share those very qualitative and quantitative parameters of engineering design, particularly as it relates to multi-faceted and future oriented design practice. Discussion covers areas of case- based techniques of cognitive ergonomics, natural modeling sources, and an open architectural process of means/goal satisfaction, qualified by natural repetition, gradation, rhythm, contrast, balance, and integrity of process.

Endochondral Ossification for Enhancing Bone Regeneration: Converging Native Extracellular Matrix Biomaterials and Developmental Engineering In Vivo

PubMed Central

Dennis, S. Connor; Berkland, Cory J.; Bonewald, Lynda F.

2015-01-01

Autologous bone grafting (ABG) remains entrenched as the gold standard of treatment in bone regenerative surgery. Consequently, many marginally successful bone tissue engineering strategies have focused on mimicking portions of ABG's “ideal” osteoconductive, osteoinductive, and osteogenic composition resembling the late reparative stage extracellular matrix (ECM) in bone fracture repair, also known as the “hard” or “bony” callus. An alternative, less common approach that has emerged in the last decade harnesses endochondral (EC) ossification through developmental engineering principles, which acknowledges that the molecular and cellular mechanisms involved in developmental skeletogenesis, specifically EC ossification, are closely paralleled during native bone healing. EC ossification naturally occurs during the majority of bone fractures and, thus, can potentially be utilized to enhance bone regeneration for nearly any orthopedic indication, especially in avascular critical-sized defects where hypoxic conditions favor initial chondrogenesis instead of direct intramembranous ossification. The body's native EC ossification response, however, is not capable of regenerating critical-sized defects without intervention. We propose that an underexplored potential exists to regenerate bone through the native EC ossification response by utilizing strategies which mimic the initial inflammatory or fibrocartilaginous ECM (i.e., “pro-” or “soft” callus) observed in the early reparative stage of bone fracture repair. To date, the majority of strategies utilizing this approach rely on clinically burdensome in vitro cell expansion protocols. This review will focus on the confluence of two evolving areas, (1) native ECM biomaterials and (2) developmental engineering, which will attempt to overcome the technical, business, and regulatory challenges that persist in the area of bone regeneration. Significant attention will be given to native “raw” materials and ECM-based designs that provide necessary osteo- and chondro-conductive and inductive features for enhancing EC ossification. In addition, critical perspectives on existing stem cell-based therapeutic strategies will be discussed with a focus on their use as an extension of the acellular ECM-based designs for specific clinical indications. Within this framework, a novel realm of unexplored design strategies for bone tissue engineering will be introduced into the collective consciousness of the regenerative medicine field. PMID:25336144

The making of a lymphocyte: the choice among disparate cell fates and the IKAROS enigma.

PubMed

Georgopoulos, Katia

2017-03-01

Lymphocyte differentiation is set to produce myriad immune effector cells with the ability to respond to multitudinous foreign substances. The uniqueness of this developmental system lies in not only the great diversity of cellular functions that it can generate but also the ability of its differentiation intermediates and mature effector cells to expand upon demand, thereby providing lifelong immunity. Surprisingly, the goals of this developmental system are met by a relatively small group of DNA-binding transcription factors that work in concert to control the timing and magnitude of gene expression and fulfill the demands for cellular specialization, expansion, and maintenance. The cellular and molecular mechanisms through which these lineage-promoting transcription factors operate have been a focus of basic research in immunology. The mechanisms of development discerned in this effort are guiding clinical research on disorders with an immune cell base. Here, I focus on IKAROS, one of the earliest regulators of lymphoid lineage identity and a guardian of lymphocyte homeostasis. © 2017 Georgopoulos; Published by Cold Spring Harbor Laboratory Press.

Receptor tyrosine kinase mutations in developmental syndromes and cancer: two sides of the same coin

PubMed Central

McDonell, Laura M.; Kernohan, Kristin D.; Boycott, Kym M.; Sawyer, Sarah L.

2015-01-01

Receptor tyrosine kinases (RTKs) are a family of ligand-binding cell surface receptors that regulate a wide range of essential cellular activities, including proliferation, differentiation, cell-cycle progression, survival and apoptosis. As such, these proteins play an important role during development and throughout life; germline mutations in genes encoding RTKs cause several developmental syndromes, while somatic alterations contribute to the pathogenesis of many aggressive cancers. This creates an interesting paradigm in which mutation timing, type and location in a gene leads to different cell signaling and biological responses, and ultimately phenotypic outcomes. In this review, we highlight the roles of RTKs in developmental disorders and cancer. The multifaceted roles of these receptors, their genetic signatures and their signaling during developmental morphogenesis and oncogenesis are discussed. Additionally, we propose that comparative analysis of RTK mutations responsible for developmental syndromes may shed light on those driving tumorigenesis. PMID:26152202

78 FR 64229 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-28

... Committee: AIDS and Related Research Integrated Review Group; AIDS Molecular and Cellular Biology Study...; Fellowships: Cell Biology, Developmental Biology and Bioengineering. Date: November 18-19, 2013. Time: 10:00 a...

Mechanisms and pathways of growth failure in primordial dwarfism.

PubMed

Klingseisen, Anna; Jackson, Andrew P

2011-10-01

The greatest difference between species is size; however, the developmental mechanisms determining organism growth remain poorly understood. Primordial dwarfism is a group of human single-gene disorders with extreme global growth failure (which includes Seckel syndrome, microcephalic osteodysplastic primordial dwarfism I [MOPD] types I and II, and Meier-Gorlin syndrome). Ten genes have now been identified for microcephalic primordial dwarfism, encoding proteins involved in fundamental cellular processes including genome replication (ORC1 [origin recognition complex 1], ORC4, ORC6, CDT1, and CDC6), DNA damage response (ATR [ataxia-telangiectasia and Rad3-related]), mRNA splicing (U4atac), and centrosome function (CEP152, PCNT, and CPAP). Here, we review the cellular and developmental mechanisms underlying the pathogenesis of these conditions and address whether further study of these genes could provide novel insight into the physiological regulation of organism growth.

Imaging C. elegans embryos using an epifluorescent microscope and open source software.

PubMed

Verbrugghe, Koen J C; Chan, Raymond C

2011-03-24

Cellular processes, such as chromosome assembly, segregation and cytokinesis,are inherently dynamic. Time-lapse imaging of living cells, using fluorescent-labeled reporter proteins or differential interference contrast (DIC) microscopy, allows for the examination of the temporal progression of these dynamic events which is otherwise inferred from analysis of fixed samples(1,2). Moreover, the study of the developmental regulations of cellular processes necessitates conducting time-lapse experiments on an intact organism during development. The Caenorhabiditis elegans embryo is light-transparent and has a rapid, invariant developmental program with a known cell lineage(3), thus providing an ideal experiment model for studying questions in cell biology(4,5)and development(6-9). C. elegans is amendable to genetic manipulation by forward genetics (based on random mutagenesis(10,11)) and reverse genetics to target specific genes (based on RNAi-mediated interference and targeted mutagenesis(12-15)). In addition, transgenic animals can be readily created to express fluorescently tagged proteins or reporters(16,17). These traits combine to make it easy to identify the genetic pathways regulating fundamental cellular and developmental processes in vivo(18-21). In this protocol we present methods for live imaging of C. elegans embryos using DIC optics or GFP fluorescence on a compound epifluorescent microscope. We demonstrate the ease with which readily available microscopes, typically used for fixed sample imaging, can also be applied for time-lapse analysis using open-source software to automate the imaging process.

Developmental Dyslexia: The Visual Attention Span Deficit Hypothesis

ERIC Educational Resources Information Center

Bosse, Marie-Line; Tainturier, Marie Josephe; Valdois, Sylviane

2007-01-01

The visual attention (VA) span is defined as the amount of distinct visual elements which can be processed in parallel in a multi-element array. Both recent empirical data and theoretical accounts suggest that a VA span deficit might contribute to developmental dyslexia, independently of a phonological disorder. In this study, this hypothesis was…

Developmentally Responsive Teacher Practices across the Middle-to-High-School Transition

ERIC Educational Resources Information Center

Ellerbrock, Cheryl R.; Abbas, Bridget; DiCicco, Michael

2014-01-01

In this year-long qualitative multi-site case study, researchers identified how eighth and ninth-grade teacher practices may support students' basic and developmental needs across the middle-to-high-school transition. Data were collected throughout 2009, including individual interviews, focus group interviews, observations, and artifact data of 23…

Choreographing Learning in Developmental Psychology Utilising Multi-Generational Genograms and Reflective Journal Writing

ERIC Educational Resources Information Center

van Schalkwyk, Gertina J.

2007-01-01

Teaching a complex topic, such as lifespan developmental psychology, challenges most lecturers to find ways to produce and develop adequately students' ability to integrate theoretical knowledge and an understanding of psychosocial issues in everyday life. In this paper, I will explain the possibilities of tools from practice in creating and…

Organization and function of the actin cytoskeleton in developing root cells.

PubMed

Blancaflor, Elison B; Wang, Yuh-Shuh; Motes, Christy M

2006-01-01

The actin cytoskeleton is a highly dynamic structure, which mediates various cellular functions in large part through accessory proteins that tilt the balance between monomeric G-actin and filamentous actin (F-actin) or by facilitating interactions between actin and the plasma membrane, microtubules, and other organelles. Roots have become an attractive model to study actin in plant development because of their simple anatomy and accessibility of some root cell types such as root hairs for microscopic analyses. Roots also exhibit a remarkable developmental plasticity and possess a delicate sensory system that is easily manipulated, so that one can design experiments addressing a range of important biological questions. Many facets of root development can be regulated by the diverse actin network found in the various root developmental regions. Various molecules impinge on this actin scaffold to define how a particular root cell type grows or responds to a specific environmental signal. Although advances in genomics are leading the way toward elucidating actin function in roots, more significant strides will be realized when such tools are combined with improved methodologies for accurately depicting how actin is organized in plant cells.

3D Visualization of Developmental Toxicity of 2,4,6-Trinitrotoluene in Zebrafish Embryogenesis Using Light-Sheet Microscopy

PubMed Central

Eum, Juneyong; Kwak, Jina; Kim, Hee Joung; Ki, Seoyoung; Lee, Kooyeon; Raslan, Ahmed A.; Park, Ok Kyu; Chowdhury, Md Ashraf Uddin; Her, Song; Kee, Yun; Kwon, Seung-Hae; Hwang, Byung Joon

2016-01-01

Environmental contamination by trinitrotoluene is of global concern due to its widespread use in military ordnance and commercial explosives. Despite known long-term persistence in groundwater and soil, the toxicological profile of trinitrotoluene and other explosive wastes have not been systematically measured using in vivo biological assays. Zebrafish embryos are ideal model vertebrates for high-throughput toxicity screening and live in vivo imaging due to their small size and transparency during embryogenesis. Here, we used Single Plane Illumination Microscopy (SPIM)/light sheet microscopy to assess the developmental toxicity of explosive-contaminated water in zebrafish embryos and report 2,4,6-trinitrotoluene-associated developmental abnormalities, including defects in heart formation and circulation, in 3D. Levels of apoptotic cell death were higher in the actively developing tissues of trinitrotoluene-treated embryos than controls. Live 3D imaging of heart tube development at cellular resolution by light-sheet microscopy revealed trinitrotoluene-associated cardiac toxicity, including hypoplastic heart chamber formation and cardiac looping defects, while the real time PCR (polymerase chain reaction) quantitatively measured the molecular changes in the heart and blood development supporting the developmental defects at the molecular level. Identification of cellular toxicity in zebrafish using the state-of-the-art 3D imaging system could form the basis of a sensitive biosensor for environmental contaminants and be further valued by combining it with molecular analysis. PMID:27869673

MultiMetEval: Comparative and Multi-Objective Analysis of Genome-Scale Metabolic Models

PubMed Central

Gevorgyan, Albert; Kierzek, Andrzej M.; Breitling, Rainer; Takano, Eriko

2012-01-01

Comparative metabolic modelling is emerging as a novel field, supported by the development of reliable and standardized approaches for constructing genome-scale metabolic models in high throughput. New software solutions are needed to allow efficient comparative analysis of multiple models in the context of multiple cellular objectives. Here, we present the user-friendly software framework Multi-Metabolic Evaluator (MultiMetEval), built upon SurreyFBA, which allows the user to compose collections of metabolic models that together can be subjected to flux balance analysis. Additionally, MultiMetEval implements functionalities for multi-objective analysis by calculating the Pareto front between two cellular objectives. Using a previously generated dataset of 38 actinobacterial genome-scale metabolic models, we show how these approaches can lead to exciting novel insights. Firstly, after incorporating several pathways for the biosynthesis of natural products into each of these models, comparative flux balance analysis predicted that species like Streptomyces that harbour the highest diversity of secondary metabolite biosynthetic gene clusters in their genomes do not necessarily have the metabolic network topology most suitable for compound overproduction. Secondly, multi-objective analysis of biomass production and natural product biosynthesis in these actinobacteria shows that the well-studied occurrence of discrete metabolic switches during the change of cellular objectives is inherent to their metabolic network architecture. Comparative and multi-objective modelling can lead to insights that could not be obtained by normal flux balance analyses. MultiMetEval provides a powerful platform that makes these analyses straightforward for biologists. Sources and binaries of MultiMetEval are freely available from https://github.com/PiotrZakrzewski/MetEval/downloads. PMID:23272111

Cellular phone enabled non-invasive tissue classifier.

PubMed

Laufer, Shlomi; Rubinsky, Boris

2009-01-01

Cellular phone technology is emerging as an important tool in the effort to provide advanced medical care to the majority of the world population currently without access to such care. In this study, we show that non-invasive electrical measurements and the use of classifier software can be combined with cellular phone technology to produce inexpensive tissue characterization. This concept was demonstrated by the use of a Support Vector Machine (SVM) classifier to distinguish through the cellular phone between heart and kidney tissue via the non-invasive multi-frequency electrical measurements acquired around the tissues. After the measurements were performed at a remote site, the raw data were transmitted through the cellular phone to a central computational site and the classifier was applied to the raw data. The results of the tissue analysis were returned to the remote data measurement site. The classifiers correctly determined the tissue type with a specificity of over 90%. When used for the detection of malignant tumors, classifiers can be designed to produce false positives in order to ensure that no tumors will be missed. This mode of operation has applications in remote non-invasive tissue diagnostics in situ in the body, in combination with medical imaging, as well as in remote diagnostics of biopsy samples in vitro.

Computer Modeling of the Earliest Cellular Structures and Functions

NASA Technical Reports Server (NTRS)

Pohorille, Andrew; Chipot, Christophe; Schweighofer, Karl

2000-01-01

In the absence of extinct or extant record of protocells (the earliest ancestors of contemporary cells). the most direct way to test our understanding of the origin of cellular life is to construct laboratory models of protocells. Such efforts are currently underway in the NASA Astrobiology Program. They are accompanied by computational studies aimed at explaining self-organization of simple molecules into ordered structures and developing designs for molecules that perform proto-cellular functions. Many of these functions, such as import of nutrients, capture and storage of energy. and response to changes in the environment are carried out by proteins bound to membrane< We will discuss a series of large-scale, molecular-level computer simulations which demonstrate (a) how small proteins (peptides) organize themselves into ordered structures at water-membrane interfaces and insert into membranes, (b) how these peptides aggregate to form membrane-spanning structures (eg. channels), and (c) by what mechanisms such aggregates perform essential proto-cellular functions, such as proton transport of protons across cell walls, a key step in cellular bioenergetics. The simulations were performed using the molecular dynamics method, in which Newton's equations of motion for each item in the system are solved iteratively. The problems of interest required simulations on multi-nanosecond time scales, which corresponded to 10(exp 6)-10(exp 8) time steps.

Cellular Phone Enabled Non-Invasive Tissue Classifier

PubMed Central

Laufer, Shlomi; Rubinsky, Boris

2009-01-01

Cellular phone technology is emerging as an important tool in the effort to provide advanced medical care to the majority of the world population currently without access to such care. In this study, we show that non-invasive electrical measurements and the use of classifier software can be combined with cellular phone technology to produce inexpensive tissue characterization. This concept was demonstrated by the use of a Support Vector Machine (SVM) classifier to distinguish through the cellular phone between heart and kidney tissue via the non-invasive multi-frequency electrical measurements acquired around the tissues. After the measurements were performed at a remote site, the raw data were transmitted through the cellular phone to a central computational site and the classifier was applied to the raw data. The results of the tissue analysis were returned to the remote data measurement site. The classifiers correctly determined the tissue type with a specificity of over 90%. When used for the detection of malignant tumors, classifiers can be designed to produce false positives in order to ensure that no tumors will be missed. This mode of operation has applications in remote non-invasive tissue diagnostics in situ in the body, in combination with medical imaging, as well as in remote diagnostics of biopsy samples in vitro. PMID:19365554

Protocell design through modular compartmentalization

PubMed Central

Miller, David; Booth, Paula J.; Seddon, John M.; Templer, Richard H.; Law, Robert V.; Woscholski, Rudiger; Ces, Oscar; Barter, Laura M. C.

2013-01-01

De novo synthetic biological design has the potential to significantly impact upon applications such as energy generation and nanofabrication. Current designs for constructing organisms from component parts are typically limited in scope, as they utilize a cut-and-paste ideology to create simple stepwise engineered protein-signalling pathways. We propose the addition of a new design element that segregates components into lipid-bound ‘proto-organelles’, which are interfaced with response elements and housed within a synthetic protocell. This design is inspired by living cells, which utilize multiple types of signalling molecules to facilitate communication between isolated compartments. This paper presents our design and validation of the components required for a simple multi-compartment protocell machine, for coupling a light transducer to a gene expression system. This represents a general design concept for the compartmentalization of different types of artificial cellular machinery and the utilization of non-protein signal molecules for signal transduction. PMID:23925982

Protocell design through modular compartmentalization.

PubMed

Miller, David; Booth, Paula J; Seddon, John M; Templer, Richard H; Law, Robert V; Woscholski, Rudiger; Ces, Oscar; Barter, Laura M C

2013-10-06

De novo synthetic biological design has the potential to significantly impact upon applications such as energy generation and nanofabrication. Current designs for constructing organisms from component parts are typically limited in scope, as they utilize a cut-and-paste ideology to create simple stepwise engineered protein-signalling pathways. We propose the addition of a new design element that segregates components into lipid-bound 'proto-organelles', which are interfaced with response elements and housed within a synthetic protocell. This design is inspired by living cells, which utilize multiple types of signalling molecules to facilitate communication between isolated compartments. This paper presents our design and validation of the components required for a simple multi-compartment protocell machine, for coupling a light transducer to a gene expression system. This represents a general design concept for the compartmentalization of different types of artificial cellular machinery and the utilization of non-protein signal molecules for signal transduction.

76 FR 30736 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-26

... personal privacy. Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review.... 93.306, Comparative Medicine; 93.333, Clinical Research, 93.306, 93.333, 93.337, 93.393-93.396, 93...

Active Cellular Mechanics and its Consequences for Animal Development

NASA Astrophysics Data System (ADS)

Noll, Nicholas B.

A central goal of developmental biology is to understand how an organism shapes itself, a process referred to as morphogenesis. While the molecular components critical to determining the initial body plan have been well characterized, the control of the subsequent dynamics of cellular rearrangements which ultimately shape the organism are far less understood. A major roadblock to a more complete picture of morphogenesis is the inability to measure tissue-scale mechanics throughout development and thus answer fundamental questions: How is the mechanical state of the cell regulated by local protein expression and global pattering? In what way does stress feedback onto the larger developmental program? In this dissertation, we begin to approach these questions through the introduction and analysis of a multi-scale model of epithelial mechanics which explicitly connects cytoskeletal protein activity to tissue-level stress. In Chapter 2, we introduce the discrete Active Tension Network (ATN) model of cellular mechanics. ATNs are tissues that satisfy two primary assumptions: that the mechanical balance of cells is dominated by cortical tension and that myosin actively remodels the actin cytoskeleton in a stress-dependent manner. Remarkably, the interplay of these features allows for angle-preserving, i.e. 'isogonal', dilations or contractions of local cell geometry that do not generate stress. Asymptotically this model is stabilized provided there is mechanical feedback on expression of myosin within the cell; we take this to be a strong prediction to be tested. The ATN model exposes a fundamental connection between equilibrium cell geometry and its underlying force network. In Chapter 3, we relax the tension-net approximation and demonstrate that at equilibrium, epithelial tissues with non-uniform pressure have non-trivial geometric constraints that imply the network is described by a weighted `dual' triangulation. We show that the dual triangulation encodes all information about the mechanical state of an epithelial tissue. Utilizing the stress-geometry 'duality', we formulate a local "Mechanical Inference" of cellular-level stress using solely cell geometry that dramatically improves over past image-based inference techniques. In Chapter 4, we generalize the ATN model to explore the controlled re-arrangement of cells within epithelial tissues. This requires us to explicitly consider the effects of cadherin mediated adhesion, and its regulation, on tissue morphogenesis. We find that positive feedback between myosin and cortical tension, along with traction-dependent depletion of cytoskeletal cadherin is sufficient to recapitulate the morphogenetic movement of cells observed during convergent extension of the lateral ectoderm during Drosophila embryogenesis. Statistical analyses of live-imaging data supports the fundamentals of the model. Chapter 5 focuses on morphogenesis at a mesoscopic scale by coarse-graining the cellular ATN model. Under this limit, we expect an epithelial tissue should behave as an effective viscous, compressible fluid driven by myosin gradients on intermediate time-scales. Theoretical predictions are empirically tested against in-toto microscopy data obtained during early Drosophila embryogenesis.

Predicting multicellular function through multi-layer tissue networks

PubMed Central

Zitnik, Marinka; Leskovec, Jure

2017-01-01

Abstract Motivation: Understanding functions of proteins in specific human tissues is essential for insights into disease diagnostics and therapeutics, yet prediction of tissue-specific cellular function remains a critical challenge for biomedicine. Results: Here, we present OhmNet, a hierarchy-aware unsupervised node feature learning approach for multi-layer networks. We build a multi-layer network, where each layer represents molecular interactions in a different human tissue. OhmNet then automatically learns a mapping of proteins, represented as nodes, to a neural embedding-based low-dimensional space of features. OhmNet encourages sharing of similar features among proteins with similar network neighborhoods and among proteins activated in similar tissues. The algorithm generalizes prior work, which generally ignores relationships between tissues, by modeling tissue organization with a rich multiscale tissue hierarchy. We use OhmNet to study multicellular function in a multi-layer protein interaction network of 107 human tissues. In 48 tissues with known tissue-specific cellular functions, OhmNet provides more accurate predictions of cellular function than alternative approaches, and also generates more accurate hypotheses about tissue-specific protein actions. We show that taking into account the tissue hierarchy leads to improved predictive power. Remarkably, we also demonstrate that it is possible to leverage the tissue hierarchy in order to effectively transfer cellular functions to a functionally uncharacterized tissue. Overall, OhmNet moves from flat networks to multiscale models able to predict a range of phenotypes spanning cellular subsystems. Availability and implementation: Source code and datasets are available at http://snap.stanford.edu/ohmnet. Contact: jure@cs.stanford.edu PMID:28881986

Label-free proteome profiling reveals developmental-dependent patterns in young barley grains.

PubMed

Kaspar-Schoenefeld, Stephanie; Merx, Kathleen; Jozefowicz, Anna Maria; Hartmann, Anja; Seiffert, Udo; Weschke, Winfriede; Matros, Andrea; Mock, Hans-Peter

2016-06-30

Due to its importance as a cereal crop worldwide, high interest in the determination of factors influencing barley grain quality exists. This study focusses on the elucidation of protein networks affecting early grain developmental processes. NanoLC-based separation coupled to label-free MS detection was applied to gain insights into biochemical processes during five different grain developmental phases (pre-storage until storage phase, 3days to 16days after flowering). Multivariate statistics revealed two distinct developmental patterns during the analysed grain developmental phases: proteins showed either highest abundance in the middle phase of development - in the transition phase - or at later developmental stages - within the storage phase. Verification of developmental patterns observed by proteomic analysis was done by applying hypothesis-driven approaches, namely Western Blot analysis and enzyme assays. High general metabolic activity of the grain with regard to protein synthesis, cell cycle regulation, defence against oxidative stress, and energy production via photosynthesis was observed in the transition phase. Proteins upregulated in the storage phase are related towards storage protein accumulation, and interestingly to the defence of storage reserves against pathogens. A mixed regulatory pattern for most enzymes detected in our study points to regulatory mechanisms at the level of protein isoforms. In-depth understanding of early grain developmental processes of cereal caryopses is of high importance as they influence final grain weight and quality. Our knowledge about these processes is still limited, especially on proteome level. To identify key mechanisms in early barley grain development, a label-free data-independent proteomics acquisition approach has been applied. Our data clearly show, that proteins either exhibit highest expression during cellularization and the switch to the storage phase (transition phase, 5-7 DAF), or during storage product accumulation (10-16 DAF). The results highlight versatile cellular metabolic activity in the transition phase and strong convergence towards storage product accumulation in the storage phase. Notably, both phases are characterized by particular protective mechanism, such as scavenging of oxidative stress and defence against pathogens, during the transition and the storage phase, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Multi-jet propulsion organized by clonal development in a colonial siphonophore

PubMed Central

Costello, John H.; Colin, Sean P.; Gemmell, Brad J.; Dabiri, John O.; Sutherland, Kelly R.

2015-01-01

Physonect siphonophores are colonial cnidarians that are pervasive predators in many neritic and oceanic ecosystems. Physonects employ multiple, clonal medusan individuals, termed nectophores, to propel an aggregate colony. Here we show that developmental differences between clonal nectophores of the physonect Nanomia bijuga produce a division of labour in thrust and torque production that controls direction and magnitude of whole-colony swimming. Although smaller and less powerful, the position of young nectophores near the apex of the nectosome allows them to dominate torque production for turning, whereas older, larger and more powerful individuals near the base of the nectosome contribute predominantly to forward thrust production. The patterns we describe offer insight into the biomechanical success of an ecologically important and widespread colonial animal group, but, more broadly, provide basic physical understanding of a natural solution to multi-engine organization that may contribute to the expanding field of underwater-distributed propulsion vehicle design. PMID:26327286

Multi-jet propulsion organized by clonal development in a colonial siphonophore

NASA Astrophysics Data System (ADS)

Costello, John; Colin, Sean; Gemmell, Brad; Dabiri, John; Sutherland, Kelly

2015-11-01

Physonect siphonophores are colonial cnidarians that are pervasive predators in many neritic and oceanic ecosystems. Physonects employ multiple, clonal medusan individuals, termed nectophores, to propel an aggregate colony. Here we show that developmental differences between clonal nectophores of the physonect Nanomia bijuga produce a division of labor in thrust and torque production that controls direction and magnitude of whole colony swimming. Although smaller and less powerful, the position of young nectophores near the apex of the nectosome allows them to dominate torque production for turning whereas older, larger and more powerful individuals near the base of the nectosome contribute predominantly to forward thrust production. The patterns we describe offer insight into the biomechanical success of an ecologically important and widespread colonial animal group, but more broadly, provide basic physical understanding of a natural solution to multi-engine organization that may contribute to the expanding field of underwater distributed propulsion vehicle design.

Multi-jet propulsion organized by clonal development in a colonial siphonophore.

PubMed

Costello, John H; Colin, Sean P; Gemmell, Brad J; Dabiri, John O; Sutherland, Kelly R

2015-09-01

Physonect siphonophores are colonial cnidarians that are pervasive predators in many neritic and oceanic ecosystems. Physonects employ multiple, clonal medusan individuals, termed nectophores, to propel an aggregate colony. Here we show that developmental differences between clonal nectophores of the physonect Nanomia bijuga produce a division of labour in thrust and torque production that controls direction and magnitude of whole-colony swimming. Although smaller and less powerful, the position of young nectophores near the apex of the nectosome allows them to dominate torque production for turning, whereas older, larger and more powerful individuals near the base of the nectosome contribute predominantly to forward thrust production. The patterns we describe offer insight into the biomechanical success of an ecologically important and widespread colonial animal group, but, more broadly, provide basic physical understanding of a natural solution to multi-engine organization that may contribute to the expanding field of underwater-distributed propulsion vehicle design.

Multi-spectral confocal microendoscope for in-vivo imaging

NASA Astrophysics Data System (ADS)

Rouse, Andrew Robert

The concept of in-vivo multi-spectral confocal microscopy is introduced. A slit-scanning multi-spectral confocal microendoscope (MCME) was built to demonstrate the technique. The MCME employs a flexible fiber-optic catheter coupled to a custom built slit-scan confocal microscope fitted with a custom built imaging spectrometer. The catheter consists of a fiber-optic imaging bundle linked to a miniature objective and focus assembly. The design and performance of the miniature objective and focus assembly are discussed. The 3mm diameter catheter may be used on its own or routed though the instrument channel of a commercial endoscope. The confocal nature of the system provides optical sectioning with 3mum lateral resolution and 30mum axial resolution. The prism based multi-spectral detection assembly is typically configured to collect 30 spectral samples over the visible chromatic range. The spectral sampling rate varies from 4nm/pixel at 490nm to 8nm/pixel at 660nm and the minimum resolvable wavelength difference varies from 7nm to 18nm over the same spectral range. Each of these characteristics are primarily dictated by the dispersive power of the prism. The MCME is designed to examine cellular structures during optical biopsy and to exploit the diagnostic information contained within the spectral domain. The primary applications for the system include diagnosis of disease in the gastro-intestinal tract and female reproductive system. Recent data from the grayscale imaging mode are presented. Preliminary multi-spectral results from phantoms, cell cultures, and excised human tissue are presented to demonstrate the potential of in-vivo multi-spectral imaging.

Evolutionary construction by staying together and coming together.

PubMed

Tarnita, Corina E; Taubes, Clifford H; Nowak, Martin A

2013-03-07

The evolutionary trajectory of life on earth is one of increasing size and complexity. Yet the standard equations of evolutionary dynamics describe mutation and selection among similar organisms that compete on the same level of organization. Here we begin to outline a mathematical theory that might help to explore how evolution can be constructive, how natural selection can lead from lower to higher levels of organization. We distinguish two fundamental operations, which we call 'staying together' and 'coming together'. Staying together means that individuals form larger units by not separating after reproduction, while coming together means that independent individuals form aggregates. Staying together can lead to specialization and division of labor, but the developmental program must evolve in the basic unit. Coming together can be creative by combining units with different properties. Both operations have been identified in the context of multicellularity, but they have been treated very similarly. Here we point out that staying together and coming together can be found at every level of biological construction and moreover that they face different evolutionary problems. The distinction is particularly clear in the context of cooperation and defection. For staying together the stability of cooperation takes the form of a developmental error threshold, while coming together leads to evolutionary games and requires a mechanism for the evolution of cooperation. We use our models to discuss simple aspects of the evolution of protocells, eukarya, multi-cellularity and animal societies. Copyright © 2012 Elsevier Ltd. All rights reserved.

Undergraduate Psychology Students' Experiences with Creative Drama: A Multi-Case Study

ERIC Educational Resources Information Center

Wilcox, Ruth A.

2015-01-01

This qualitative multi-case study explored undergraduate psychology students' experiences participating in creative drama activities the instructor/researcher developed to teach psychological concepts. The study was conducted in three introductory and developmental courses in a mid-western community college setting. Participants (cases) included…

Design, analysis, and applications of cellular contact-aided compliant mechanisms

NASA Astrophysics Data System (ADS)

Mehta, Vipul

A new class of compliant mechanisms utilizing the benefits of cellular geometry and contact are addressed in this work. The design, analysis, fabrication and testing of such structures for high-strain and high-strength applications is the focus of the present research. Cellular structures have relatively good strength-to-weight ratios. They also have a higher strain capability than solid structures. Contact during deformation reduces failure-causing bending stresses through stress relief, thereby enabling such cellular structures to be stretched more than the corresponding structures without contact. Both analytical and numerical models are developed to represent one specific mechanism. Several candidate materials are investigated for such mechanisms. Although the allowable strain of all these materials is small, the overall strain of the contact-aided cellular mechanisms is at least an order of magnitude greater than that of the constitutive material. Application of contact to different materials yields an improvement in the global strain capacity by more than 100% relative to cellular structures without contact. Experiments are conducted to validate the models, and good agreement is found. Size optimization is carried out to maximize the stress relief and the overall strain. Two main applications are considered in the present work. One application consists of a morphing aircraft skin for adaptive structures. Different material models such as linearly elastic and multi-linear elastic are examined. For linearly elastic materials, contact-induced stress-relief is advantageous and for nonlinear elastic materials, reduction of transverse deflection due to contact is useful. The proposed contact-aided skin structure is compared with a cellular skin without contact. The contact mechanism helps to increase the morphing capacity while decreasing the structural mass. Using contact-aided cellular mechanisms, the global strain capability is increased by as much as 37%. For a fixed global strain, the optimum contact-aided structure is 15% lighter than an optimum non-contact structure. Another application involves investigation of meso-scaled cellular structures. Two different materials are considered---nanoparticulate zirconia and particulate stainless steel. The lost mold rapid infiltration forming process is utilized to fabricate free standing cellular mechanisms. The analytical model is employed to address the tradeoffs between the manufacturing constraints and to design suitable contact-aided cellular mechanisms. A custom rig is developed to test these meso-scaled parts. Force displacement characteristics are experimentally obtained and compared against those found using the analytical model. Topology optimization tools are applied to the design of compliant cellular mechanisms with and without a contact mechanism. A two-step procedure is developed. For cellular structures without contact, an inverse homogenization method is employed. The compliant mechanism is optimized to yield prescribed elasticity coefficients and achieve a large effective elastic strain. To implement a contact mechanism in the second step, the continuum model of a non-contact structure is converted into a frame model. Only the non-overlapping designs are investigated exhaustively for stress relief. A differential evolution optimizer is used to maximize the stress relief. Four cell topologies are found for different effective properties corresponding to different structural requirements. For each such topology, a contact mechanism is devised that demonstrates stress relief. One such topology resulted a stress relief as high as 36%.

Impaired Letter-String Processing in Developmental Dyslexia: What Visual-to-Phonology Code Mapping Disorder?

ERIC Educational Resources Information Center

Valdois, Sylviane; Lassus-Sangosse, Delphine; Lobier, Muriel

2012-01-01

Poor parallel letter-string processing in developmental dyslexia was taken as evidence of poor visual attention (VA) span, that is, a limitation of visual attentional resources that affects multi-character processing. However, the use of letter stimuli in oral report tasks was challenged on its capacity to highlight a VA span disorder. In…

Investigation of a Developmental Model of Risk for Depression and Suicidality Following Spousal Bereavement

ERIC Educational Resources Information Center

Johnson, Jeffrey G.; Zhang, Baohui; Prigerson, Holly G.

2008-01-01

Data from a community-based multi-wave investigation were used to examine a developmental model of risk for depression and suicidality following the death of a spouse. Measures of perceived parental affection and control during childhood were administered to 218 widowed adults 11 months after the death of the spouse. Self-esteem, spousal…

Cellular therapies for heart disease: unveiling the ethical and public policy challenges.

PubMed

Raval, Amish N; Kamp, Timothy J; Hogle, Linda F

2008-10-01

Cellular therapies have emerged as a potential revolutionary treatment for cardiovascular disease. Promising preclinical results have resulted in a flurry of basic research activity and spawned multiple clinical trials worldwide. However, the optimal cell type and delivery mode have not been determined for target patient populations. Nor have the mechanisms of benefit for the range of cellular interventions been clearly defined. Experiences to date have unveiled a myriad of ethical and public policy challenges which will affect the way researchers and clinicians make decisions for both basic and clinical research. Stem cells derived from embryos are at the forefront of the ethical and political debate, raising issues of which derivation methods are morally and socially permissible to pursue, as much as which are technically feasible. Adult stem cells are less controversial; however, important challenges exist in determining study design, cell processing, delivery mode, and target patient population. Pathways to successful commercialization and hence broad accessibility of cellular therapies for heart disease are only beginning to be explored. Comprehensive, multi-disciplinary and collaborative networks involving basic researchers, clinicians, regulatory officials and policymakers are required to share information, develop research, regulatory and policy standards and enable rational and ethical cell-based treatment approaches.

Fracture mechanics of cellular glass

NASA Technical Reports Server (NTRS)

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

1981-01-01

The fracture mechanics of cellular glasses (for the structural substrate of mirrored glass for solr concentrator reflecting panels) are discussed. Commercial and developmental cellular glasses were tested and analyzed using standard testing techniques and models developed from linear fracture mechanics. Two models describing the fracture behavior of these materials were developed. Slow crack growth behavior in cellular glass was found to be more complex than that encountered in dense glasses or ceramics. The crack velocity was found to be strongly dependent upon water vapor transport to the tip of the moving crack. The existence of a static fatigue limit was not conclusively established, however, it is speculated that slow crack growth behavior in Region 1 may be slower, by orders of magnitude, than that found in dense glasses.

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

NASA Astrophysics Data System (ADS)

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

2017-01-01

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

Chapter 14. Approaches for Evaluation of Mode of Action.

EPA Science Inventory

Cellular and molecular approaches vastly expand the possibilities for revealing the underlying mechanisms of developmental toxicity. The typical teratology screening test examines near-term fetuses after exposure throughout organogenesis and evaluates the potential for an exposur...

The body electric 2.0: recent advances in developmental bioelectricity for regenerative and synthetic bioengineering.

PubMed

Mathews, Juanita; Levin, Michael

2018-04-20

Breakthroughs in biomedicine and synthetic bioengineering require predictive, rational control over anatomical structure and function. Recent successes in manipulating cellular and molecular hardware have not been matched by progress in understanding the patterning software implemented during embryogenesis and regeneration. A fundamental capability gap is driving desired changes in growth and form to address birth defects and traumatic injury. Here we review new tools, results, and conceptual advances in an exciting emerging field: endogenous non-neural bioelectric signaling, which enables cellular collectives to make global decisions and implement large-scale pattern homeostasis. Spatially distributed electric circuits regulate gene expression, organ morphogenesis, and body-wide axial patterning. Developmental bioelectricity facilitates the interface to organ-level modular control points that direct patterning in vivo. Cracking the bioelectric code will enable transformative progress in bioengineering and regenerative medicine. Copyright © 2018 Elsevier Ltd. All rights reserved.

Single-nucleus analysis of accessible chromatin in developing mouse forebrain reveals cell-type-specific transcriptional regulation.

PubMed

Preissl, Sebastian; Fang, Rongxin; Huang, Hui; Zhao, Yuan; Raviram, Ramya; Gorkin, David U; Zhang, Yanxiao; Sos, Brandon C; Afzal, Veena; Dickel, Diane E; Kuan, Samantha; Visel, Axel; Pennacchio, Len A; Zhang, Kun; Ren, Bing

2018-03-01

Analysis of chromatin accessibility can reveal transcriptional regulatory sequences, but heterogeneity of primary tissues poses a significant challenge in mapping the precise chromatin landscape in specific cell types. Here we report single-nucleus ATAC-seq, a combinatorial barcoding-assisted single-cell assay for transposase-accessible chromatin that is optimized for use on flash-frozen primary tissue samples. We apply this technique to the mouse forebrain through eight developmental stages. Through analysis of more than 15,000 nuclei, we identify 20 distinct cell populations corresponding to major neuronal and non-neuronal cell types. We further define cell-type-specific transcriptional regulatory sequences, infer potential master transcriptional regulators and delineate developmental changes in forebrain cellular composition. Our results provide insight into the molecular and cellular dynamics that underlie forebrain development in the mouse and establish technical and analytical frameworks that are broadly applicable to other heterogeneous tissues.

TAM receptor signaling in development.

PubMed

Burstyn-Cohen, Tal

2017-01-01

TYRO3, AXL and MERTK comprise the TAM family of receptor protein tyrosine kinases. Activated by their ligands, protein S (PROS1) and growth-arrest-specific 6 (GAS6), they mediate numerous cellular functions throughout development and adulthood. Expressed by a myriad of cell types and tissues, they have been implicated in homeostatic regulation of the immune, nervous, vascular, bone and reproductive systems. The loss-of-function of TAM signaling in adult tissues culminates in the destruction of tissue homeostasis and diseased states, while TAM gain-of-function in various tumors promotes cancer phenotypes. Combinatorial ligand-receptor interactions may elicit different molecular and cellular responses. Many of the TAM regulatory functions are essentially developmental, taking place both during embryogenesis and postnatally. This review highlights current knowledge on the role of TAM receptors and their ligands during these developmental processes in the immune, nervous, vascular and reproductive systems.

Mechanisms and pathways of growth failure in primordial dwarfism

PubMed Central

Klingseisen, Anna; Jackson, Andrew P.

2011-01-01

The greatest difference between species is size; however, the developmental mechanisms determining organism growth remain poorly understood. Primordial dwarfism is a group of human single-gene disorders with extreme global growth failure (which includes Seckel syndrome, microcephalic osteodysplastic primordial dwarfism I [MOPD] types I and II, and Meier-Gorlin syndrome). Ten genes have now been identified for microcephalic primordial dwarfism, encoding proteins involved in fundamental cellular processes including genome replication (ORC1 [origin recognition complex 1], ORC4, ORC6, CDT1, and CDC6), DNA damage response (ATR [ataxia-telangiectasia and Rad3-related]), mRNA splicing (U4atac), and centrosome function (CEP152, PCNT, and CPAP). Here, we review the cellular and developmental mechanisms underlying the pathogenesis of these conditions and address whether further study of these genes could provide novel insight into the physiological regulation of organism growth. PMID:21979914

Quantitation of Cellular Dynamics in Growing Arabidopsis Roots with Light Sheet Microscopy

PubMed Central

Birnbaum, Kenneth D.; Leibler, Stanislas

2011-01-01

To understand dynamic developmental processes, living tissues have to be imaged frequently and for extended periods of time. Root development is extensively studied at cellular resolution to understand basic mechanisms underlying pattern formation and maintenance in plants. Unfortunately, ensuring continuous specimen access, while preserving physiological conditions and preventing photo-damage, poses major barriers to measurements of cellular dynamics in growing organs such as plant roots. We present a system that integrates optical sectioning through light sheet fluorescence microscopy with hydroponic culture that enables us to image, at cellular resolution, a vertically growing Arabidopsis root every few minutes and for several consecutive days. We describe novel automated routines to track the root tip as it grows, to track cellular nuclei and to identify cell divisions. We demonstrate the system's capabilities by collecting data on divisions and nuclear dynamics. PMID:21731697

Principles of Unconventional Myosin Function and Targeting

PubMed Central

Hartman, M. Amanda; Finan, Dina; Sivaramakrishnan, Sivaraj; Spudich, James A.

2016-01-01

Unconventional myosins are a superfamily of actin-based motors implicated in diverse cellular processes. In recent years, much progress has been made in describing their biophysical properties, and headway has been made into analyzing their cellular functions. Here, we focus on the principles that guide in vivo motor function and targeting to specific cellular locations. Rather than describe each motor comprehensively, we outline the major themes that emerge from research across the superfamily and use specific examples to illustrate each. In presenting the data in this format, we seek to identify open questions in each field as well as to point out commonalities between them. To advance our understanding of myosins’ roles in vivo, clearly we must identify their cellular cargoes and the protein complexes that regulate motor attachment to fully appreciate their functions on the cellular and developmental levels. PMID:21639800

Deposition dynamics of multi-solvent bioinks

NASA Astrophysics Data System (ADS)

Kaneelil, Paul; Pack, Min; Cui, Chunxiao; Han, Li-Hsin; Sun, Ying

2017-11-01

Inkjet printing cellular scaffolds using bioinks is gaining popularity due to the advancement of printing technology as well as the growing demands of regenerative medicine. Numerous studies have been conducted on printing scaffolds of biomimetic structures that support the cell production of human tissues. However, the underlying physics of the deposition dynamics of bioinks remains elusive. Of particular interest is the unclear deposition dynamics of multi-solvent bioinks, which is often used to tune the micro-architecture formation. Here we systematically studied the effects of jetting frequency, solvent properties, substrate wettability, and temperature on the three-dimensional deposition patterns of bioinks made of Methacrylated Gelatin and Carboxylated Gelatin. The microflows inside the inkjet-printed picolitre drops were visualized using fluorescence tracer particles to decipher the complex processes of multi-solvent evaporation and solute self-assembly. The evolution of droplet shape was observed using interferometry. With the integrated techniques, the interplay of solvent evaporation, biopolymer deposition, and multi-drop interactions were directly observed for various ink and substrate properties, and printing conditions. Such knowledge enables the design and fabrication of a variety of tissue engineering scaffolds for potential use in regenerative medicine.

Robust and irreversible development in cell society as a general consequence of intra-inter dynamics

NASA Astrophysics Data System (ADS)

Kaneko, Kunihiko; Furusawa, Chikara

2000-05-01

A dynamical systems scenario for developmental cell biology is proposed, based on numerical studies of a system with interacting units with internal dynamics and reproduction. Diversification, formation of discrete and recursive types, and rules for differentiation are found as a natural consequence of such a system. “Stem cells” that either proliferate or differentiate to different types stochastically are found to appear when intra-cellular dynamics are chaotic. Robustness of the developmental process against microscopic and macroscopic perturbations is shown to be a natural consequence of such intra-inter dynamics, while irreversibility in developmental process is discussed in terms of the gain of stability, loss of diversity and chaotic instability.

Intervention Strategies for Dealing with Multi-Problem Families.

ERIC Educational Resources Information Center

Kloss, James; And Others

This paper describes the Primary Prevention Project (PPP), a demonstration program of the Mendota Mental Health Institute in Madison, Wisconsin which provides services to multi-problem families with children under 3 years of age in order to prevent abuse and neglect, developmental delay, or future socio-emotional difficulty. The project's…

Development of a Multi-Dimensional Scale for PDD and ADHD

ERIC Educational Resources Information Center

Funabiki, Yasuko; Kawagishi, Hisaya; Uwatoko, Teruhisa; Yoshimura, Sayaka; Murai, Toshiya

2011-01-01

A novel assessment scale, the multi-dimensional scale for pervasive developmental disorder (PDD) and attention-deficit/hyperactivity disorder (ADHD) (MSPA), is reported. Existing assessment scales are intended to establish each diagnosis. However, the diagnosis by itself does not always capture individual characteristics or indicate the level of…

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

Garige, Mamatha; Walters, Eric, E-mail: ewalters@howard.edu

The molecular basis for nutraceutical properties of the polyphenol curcumin (Curcuma longa, Turmeric) is complex, affecting multiple factors that regulate cell signaling and homeostasis. Here, we report the effect of curcumin on cellular and developmental mechanisms in the eukaryotic model, Dictyostelium discoideum. Dictyostelium proliferation was inhibited in the presence of curcumin, which also suppressed the prestarvation marker, discoidin I, members of the yakA-mediated developmental signaling pathway, and expression of the extracellular matrix/cell adhesion proteins (DdCAD and csA). This resulted in delayed chemotaxis, adhesion, and development of the organism. In contrast to the inhibitory effects on developmental genes, curcumin induced gstAmore » gene expression, overall GST activity, and generated production of reactive oxygen species. These studies expand our knowledge of developmental and biochemical signaling influenced by curcumin, and lends greater consideration of GST enzyme function in eukaryotic cell signaling, development, and differentiation.« less

Designing Meaningful Developmental Reform. Research Overview

ERIC Educational Resources Information Center

Jaggars, Shanna Smith; Hodara, Michelle; Stacey, Georgia West

2013-01-01

This practitioner packet is designed to help community college administrators implement reforms to developmental education at their colleges. It reviews common impediments to developmental reform and presents data that supports directions colleges can take to create a system of developmental education that might serve students more effectively.…

Comparison of cellular toxicity between multi-walled carbon nanotubes and onion-like shell-shaped carbon nanoparticles

NASA Astrophysics Data System (ADS)

Kang, Seunghyon; Kim, Ji-Eun; Kim, Daegyu; Woo, Chang Gyu; Pikhitsa, Peter V.; Cho, Myung-Haing; Choi, Mansoo

2015-09-01

The cellular toxicity of multi-walled carbon nanotubes (MWCNTs) and onion-like shell-shaped carbon nanoparticles (SCNPs) was investigated by analyzing the comparative cell viability. For the reasonable comparison, physicochemical characteristics were controlled thoroughly such as crystallinity, carbon bonding characteristic, hydrodynamic diameter, and metal contents of the particles. To understand relation between cellular toxicity of the particles and generation of reactive oxygen species (ROS), we measured unpaired singlet electrons of the particles and intracellular ROS, and analyzed cellular toxicity with/without the antioxidant N-acetylcysteine (NAC). Regardless of the presence of NAC, the cellular toxicity of SCNPs was found to be lower than that of MWCNTs. Since both particles show similar crystallinity, hydrodynamic size, and Raman signal with negligible contribution of remnant metal particles, the difference in cell viability would be ascribed to the difference in morphology, i.e., spherical shape (aspect ratio of one) for SCNP and elongated shape (high aspect ratio) for MWCNT.

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

PubMed

Tsukahara, Tamotsu; Haniu, Hisao

2011-06-01

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

Non-coding RNA networks in cancer.

PubMed

Anastasiadou, Eleni; Jacob, Leni S; Slack, Frank J

2018-01-01

Thousands of unique non-coding RNA (ncRNA) sequences exist within cells. Work from the past decade has altered our perception of ncRNAs from 'junk' transcriptional products to functional regulatory molecules that mediate cellular processes including chromatin remodelling, transcription, post-transcriptional modifications and signal transduction. The networks in which ncRNAs engage can influence numerous molecular targets to drive specific cell biological responses and fates. Consequently, ncRNAs act as key regulators of physiological programmes in developmental and disease contexts. Particularly relevant in cancer, ncRNAs have been identified as oncogenic drivers and tumour suppressors in every major cancer type. Thus, a deeper understanding of the complex networks of interactions that ncRNAs coordinate would provide a unique opportunity to design better therapeutic interventions.

Early warning of illegal development for protected areas by integrating cellular automata with neural networks.

PubMed

Li, Xia; Lao, Chunhua; Liu, Yilun; Liu, Xiaoping; Chen, Yimin; Li, Shaoying; Ai, Bing; He, Zijian

2013-11-30

Ecological security has become a major issue under fast urbanization in China. As the first two cities in this country, Shenzhen and Dongguan issued the ordinance of Eco-designated Line of Control (ELC) to "wire" ecologically important areas for strict protection in 2005 and 2009 respectively. Early warning systems (EWS) are a useful tool for assisting the implementation ELC. In this study, a multi-model approach is proposed for the early warning of illegal development by integrating cellular automata (CA) and artificial neural networks (ANN). The objective is to prevent the ecological risks or catastrophe caused by such development at an early stage. The integrated model is calibrated by using the empirical information from both remote sensing and handheld GPS (global positioning systems). The MAR indicator which is the ratio of missing alarms to all the warnings is proposed for better assessment of the model performance. It is found that the fast urban development has caused significant threats to natural-area protection in the study area. The integration of CA, ANN and GPS provides a powerful tool for describing and predicting illegal development which is in highly non-linear and fragmented forms. The comparison shows that this multi-model approach has much better performances than the single-model approach for the early warning. Compared with the single models of CA and ANN, this integrated multi-model can improve the value of MAR by 65.48% and 5.17% respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

A novel multi-drug metronomic chemotherapy significantly delays tumor growth in mice.

PubMed

Tagliamonte, Maria; Petrizzo, Annacarmen; Napolitano, Maria; Luciano, Antonio; Rea, Domenica; Barbieri, Antonio; Arra, Claudio; Maiolino, Piera; Tornesello, Marialina; Ciliberto, Gennaro; Buonaguro, Franco M; Buonaguro, Luigi

2016-02-24

The tumor immunosuppressive microenvironment represents a major obstacle to an effective tumor-specific cellular immune response. In the present study, the counterbalance effect of a novel metronomic chemotherapy protocol on such an immunosuppressive microenvironment was evaluated in a mouse model upon sub-cutaneous ectopic implantation of B16 melanoma cells. The chemotherapy consisted of a novel multi-drug cocktail including taxanes and alkylating agents, administered in a daily metronomic fashion. The newly designed strategy was shown to be safe, well tolerated and significantly efficacious. Treated animals showed a remarkable delay in tumor growth and prolonged survival as compared to control group. Such an effect was directly correlated with CD4(+) T cell reduction and CD8(+) T cell increase. Furthermore, a significant reduction in the percentage of both CD25(+)FoxP3(+) and CD25(+)CD127(low) regulatory T cell population was found both in the spleens and in the tumor lesions. Finally, the metronomic chemotherapy induced an intrinsic CD8(+) T cell response specific to B16 naturally expressed Trp2 TAA. The novel multi-drug daily metronomic chemotherapy evaluated in the present study was very effective in counterbalancing the immunosuppressive tumor microenvironment. Consequently, the intrinsic anti-tumor T cell immunity could exert its function, targeting specific TAA and significantly containing tumor growth. Overall, the results show that this represents a promising adjuvant approach to significantly enhance efficacy of intrinsic or vaccine-elicited tumor-specific cellular immunity.

pLoc-mPlant: predict subcellular localization of multi-location plant proteins by incorporating the optimal GO information into general PseAAC.

PubMed

Cheng, Xiang; Xiao, Xuan; Chou, Kuo-Chen

2017-08-22

One of the fundamental goals in cellular biochemistry is to identify the functions of proteins in the context of compartments that organize them in the cellular environment. To realize this, it is indispensable to develop an automated method for fast and accurate identification of the subcellular locations of uncharacterized proteins. The current study is focused on plant protein subcellular location prediction based on the sequence information alone. Although considerable efforts have been made in this regard, the problem is far from being solved yet. Most of the existing methods can be used to deal with single-location proteins only. Actually, proteins with multi-locations may have some special biological functions. This kind of multiplex protein is particularly important for both basic research and drug design. Using the multi-label theory, we present a new predictor called "pLoc-mPlant" by extracting the optimal GO (Gene Ontology) information into the Chou's general PseAAC (Pseudo Amino Acid Composition). Rigorous cross-validation on the same stringent benchmark dataset indicated that the proposed pLoc-mPlant predictor is remarkably superior to iLoc-Plant, the state-of-the-art method for predicting plant protein subcellular localization. To maximize the convenience of most experimental scientists, a user-friendly web-server for the new predictor has been established at , by which users can easily get their desired results without the need to go through the complicated mathematics involved.

Can mechanics control pattern formation in plants?

PubMed

Dumais, Jacques

2007-02-01

Development of the plant body entails many pattern forming events at scales ranging from the cellular level to the whole plant. Recent evidence suggests that mechanical forces play a role in establishing some of these patterns. The development of cellular configurations in glandular trichomes and the rippling of leaf surfaces are discussed in depth to illustrate how intricate patterns can emerge from simple and well-established molecular and cellular processes. The ability of plants to sense and transduce mechanical signals suggests that complex interactions between mechanics and chemistry are possible during plant development. The inclusion of mechanics alongside traditional molecular controls offers a more comprehensive view of developmental processes.

Gene regulatory networks and the underlying biology of developmental toxicity

EPA Science Inventory

Embryonic cells are specified by large-scale networks of functionally linked regulatory genes. Knowledge of the relevant gene regulatory networks is essential for understanding phenotypic heterogeneity that emerges from disruption of molecular functions, cellular processes or sig...

vEmbryo In Silico Models: Predicting Vascular Developmental Toxicity

EPA Science Inventory

The cardiovascular system is the first to function in the vertebrate embryo, reflecting the critical need for nutrient delivery and waste removal during organogenesis. Blood vessel development occurs by complex interacting signaling networks, including extra-cellular matrix remod...

Nicotinic α5 Subunits Drive Developmental Changes in the Activation and Morphology of Prefrontal Cortex Layer VI Neurons

PubMed Central

Bailey, Craig D.C.; Alves, Nyresa C.; Nashmi, Raad; De Biasi, Mariella; Lambe, Evelyn K.

2013-01-01

Background Nicotinic signaling in prefrontal layer VI pyramidal neurons is important to the function of mature attention systems. The normal incorporation of α5 subunits into α4β2* nicotinic acetylcholine receptors augments nicotinic signaling in these neurons and is required for normal attention performance in adult mice. However, the role of α5 subunits in the development of the prefrontal cortex is not known. Methods We sought to answer this question by examining nicotinic currents and neuronal morphology in layer VI neurons of medial prefrontal cortex of wild-type and α5 subunit knockout (α5−/−) mice during postnatal development and in adulthood. Results In wild-type but not in α5−/− mice, there is a developmental peak in nicotinic acetylcholine currents in the third postnatal week. At this juvenile time period, the majority of neurons in all mice have long apical dendrites extending into cortical layer I. Yet, by early adulthood, wild-type but not α5−/− mice show a pronounced shift toward shorter apical dendrites. This cellular difference occurs in the absence of genotype differences in overall cortical morphology. Conclusions Normal developmental changes in nicotinic signaling and dendritic morphology in prefrontal cortex depend on α5-comprising nicotinic acetylcholine receptors. It appears that these receptors mediate a specific developmental retraction of apical dendrites in layer VI neurons. This finding provides novel insight into the cellular mechanisms underlying the known attention deficits in α5−/− mice and potentially also into the pathophysiology of developmental neuropsychiatric disorders such as attention-deficit disorder and autism. PMID:22030359

Standing between Two Worlds in Harlem: A Developmental Psychopathology Perspective of Perinatally Acquired Human Immunodeficiency Virus and Adolescence

ERIC Educational Resources Information Center

Kang, Ezer; Mellins, Claude Ann; Ng, Warren Yiu Kee; Robinson, Lisa-Gaye; Abrams, Elaine J.

2008-01-01

Perinatal HIV infection in the US continues to evolve from a fatal pediatric illness to a chronic medical condition of childhood and adolescence. Although navigating this period is influenced by multi-leveled deprivations commonly experienced by low-income minority families, HIV alters the timing and experience of developmental milestones for many…

Validating the Language Domain Subtest in a Developmental Assessment Scale for Preschool Children

ERIC Educational Resources Information Center

Wong, Anita M. -Y.; Leung, Cynthia; Siu, Elaine K. -L.; Lam, Catherine C. -C.

2012-01-01

This study reports on the validation of the language domain subtest of a developmental assessment scale for Cantonese Chinese preschool children. Three hundred and seventy eight multi-stage randomly selected children between 3;4 and 6;3 years of age were tested on the 104-item subtest. Fifty-four of these children, spreading across three age…

Developmental Pathways to Depressive Symptoms in Adolescence: A Multi-Wave Prospective Study of Negative Emotionality, Stressors, and Anxiety

ERIC Educational Resources Information Center

Barrocas, Andrea L.; Hankin, Benjamin L.

2011-01-01

This study examined two potential developmental pathways through which the temperament risk factor of negative emotionality (NE) leads to prospective increases in depressive symptoms through the mediating role of stressors and anxious symptoms in a sample of early to middle adolescents (N = 350, 6th-10th graders). The primary hypothesized model…

Developmental dyslexia: the visual attention span deficit hypothesis.

PubMed

Bosse, Marie-Line; Tainturier, Marie Josèphe; Valdois, Sylviane

2007-08-01

The visual attention (VA) span is defined as the amount of distinct visual elements which can be processed in parallel in a multi-element array. Both recent empirical data and theoretical accounts suggest that a VA span deficit might contribute to developmental dyslexia, independently of a phonological disorder. In this study, this hypothesis was assessed in two large samples of French and British dyslexic children whose performance was compared to that of chronological-age matched control children. Results of the French study show that the VA span capacities account for a substantial amount of unique variance in reading, as do phonological skills. The British study replicates this finding and further reveals that the contribution of the VA span to reading performance remains even after controlling IQ, verbal fluency, vocabulary and single letter identification skills, in addition to phoneme awareness. In both studies, most dyslexic children exhibit a selective phonological or VA span disorder. Overall, these findings support a multi-factorial view of developmental dyslexia. In many cases, developmental reading disorders do not seem to be due to phonological disorders. We propose that a VA span deficit is a likely alternative underlying cognitive deficit in dyslexia.

Vaccine strategies against Babesia bovis based on prime-boost immunizations in mice with modified vaccinia Ankara vector and recombinant proteins.

PubMed

Jaramillo Ortiz, José Manuel; Del Médico Zajac, María Paula; Zanetti, Flavia Adriana; Molinari, María Paula; Gravisaco, María José; Calamante, Gabriela; Wilkowsky, Silvina Elizabeth

2014-08-06

In this study, a recombinant modified vaccinia virus Ankara vector expressing a chimeric multi-antigen was obtained and evaluated as a candidate vaccine in homologous and heterologous prime-boost immunizations with a recombinant protein cocktail. The chimeric multi-antigen comprises immunodominant B and T cell regions of three Babesia bovis proteins. Humoral and cellular immune responses were evaluated in mice to compare the immunogenicity induced by different immunization schemes. The best vaccination scheme was achieved with a prime of protein cocktail and a boost with the recombinant virus. This scheme induced high level of specific IgG antibodies and secreted IFN and a high degree of activation of IFNγ(+) CD4(+) and CD8(+) specific T cells. This is the first report in which a novel vaccine candidate was constructed based on a rationally designed multi-antigen and evaluated in a prime-boost regime, optimizing the immune response necessary for protection against bovine babesiosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Developmental Designs: A Description of the Approach and Implementation in Schools

ERIC Educational Resources Information Center

Kwame-Ross, Terrance; Crawford, Linda; Klug, Erin

2011-01-01

This article describes the theoretical and conceptual framework upon which the Developmental Designs (DD) approach is based and four fundamental human needs especially compelling for adolescents. These are used as the foreground to explain and contextualize the Developmental Designs' 10 classroom practices and professional development…

Multi-scale Imaging of Cellular and Sub-cellular Structures using Scanning Probe Recognition Microscopy.

NASA Astrophysics Data System (ADS)

Chen, Q.; Rice, A. F.

2005-03-01

Scanning Probe Recognition Microscopy is a new scanning probe capability under development within our group to reliably return to and directly interact with a specific nanobiological feature of interest. In previous work, we have successfully recognized and classified tubular versus globular biological objects from experimental atomic force microscope images using a method based on normalized central moments [ref. 1]. In this paper we extend this work to include recognition schemes appropriate for cellular and sub-cellular structures. Globular cells containing tubular actin filaments are under investigation. Thus there are differences in external/internal shapes and scales. Continuous Wavelet Transform with a differential Gaussian mother wavelet is employed for multi- scale analysis. [ref. 1] Q. Chen, V. Ayres and L. Udpa, ``Biological Investigation Using Scanning Probe Recognition Microscopy,'' Proceedings 3rd IEEE Conference on Nanotechnology, vol. 2, p 863-865 (2003).

Exploring Autophagy in Drosophila

PubMed Central

Juhász, Gábor

2017-01-01

Autophagy is a catabolic process in eukaryotic cells promoting bulk or selective degradation of cellular components within lysosomes. In recent decades, several model systems were utilized to dissect the molecular machinery of autophagy and to identify the impact of this cellular “self-eating” process on various physiological and pathological processes. Here we briefly discuss the advantages and limitations of using the fruit fly Drosophila melanogaster, a popular model in cell and developmental biology, to apprehend the main pathway of autophagy in a complete animal. PMID:28704946

From single cells to tissue architecture-a bottom-up approach to modelling the spatio-temporal organisation of complex multi-cellular systems.

PubMed

Galle, J; Hoffmann, M; Aust, G

2009-01-01

Collective phenomena in multi-cellular assemblies can be approached on different levels of complexity. Here, we discuss a number of mathematical models which consider the dynamics of each individual cell, so-called agent-based or individual-based models (IBMs). As a special feature, these models allow to account for intracellular decision processes which are triggered by biomechanical cell-cell or cell-matrix interactions. We discuss their impact on the growth and homeostasis of multi-cellular systems as simulated by lattice-free models. Our results demonstrate that cell polarisation subsequent to cell-cell contact formation can be a source of stability in epithelial monolayers. Stroma contact-dependent regulation of tumour cell proliferation and migration is shown to result in invasion dynamics in accordance with the migrating cancer stem cell hypothesis. However, we demonstrate that different regulation mechanisms can equally well comply with present experimental results. Thus, we suggest a panel of experimental studies for the in-depth validation of the model assumptions.

An Update on ToxCast™ | Science Inventory | US EPA

EPA Pesticide Factsheets

In its first phase, ToxCast™ is profiling over 300 well-characterized chemicals (primarily pesticides) in over 400 HTS endpoints. These endpoints include biochemical assays of protein function, cell-based transcriptional reporter assays, multi-cell interaction assays, transcriptomics on primary cell cultures, and developmental assays in zebrafish embryos. Almost all of the compounds being examined in Phase 1 of ToxCast™ have been tested in traditional toxicology tests, including developmental toxicity, multi-generation studies, and sub-chronic and chronic rodent bioassays Lessons learned to date for ToxCast: Large amounts of quality HTS data can be economically obtained. Large scale data sets will be required to understand potential for biological activity. Value in having multiple assays with overlapping coverage of biological pathways and a variety of methodologies Concentration-response will be important for ultimate interpretation Data transparency will be important for acceptance. Metabolic capabilities and coverage of developmental toxicity pathways will need additional attention. Need to define the gold standard Partnerships are needed to bring critical mass and expertise.

Inter-Cellular Forces Orchestrate Contact Inhibition of Locomotion

PubMed Central

Davis, John R.; Luchici, Andrei; Mosis, Fuad; Thackery, James; Salazar, Jesus A.; Mao, Yanlan; Dunn, Graham A.; Betz, Timo; Miodownik, Mark; Stramer, Brian M.

2015-01-01

Summary Contact inhibition of locomotion (CIL) is a multifaceted process that causes many cell types to repel each other upon collision. During development, this seemingly uncoordinated reaction is a critical driver of cellular dispersion within embryonic tissues. Here, we show that Drosophila hemocytes require a precisely orchestrated CIL response for their developmental dispersal. Hemocyte collision and subsequent repulsion involves a stereotyped sequence of kinematic stages that are modulated by global changes in cytoskeletal dynamics. Tracking actin retrograde flow within hemocytes in vivo reveals synchronous reorganization of colliding actin networks through engagement of an inter-cellular adhesion. This inter-cellular actin-clutch leads to a subsequent build-up in lamellar tension, triggering the development of a transient stress fiber, which orchestrates cellular repulsion. Our findings reveal that the physical coupling of the flowing actin networks during CIL acts as a mechanotransducer, allowing cells to haptically sense each other and coordinate their behaviors. PMID:25799385

Origins of cellular geometry

PubMed Central

2011-01-01

Cells are highly complex and orderly machines, with defined shapes and a startling variety of internal organizations. Complex geometry is a feature of both free-living unicellular organisms and cells inside multicellular animals. Where does the geometry of a cell come from? Many of the same questions that arise in developmental biology can also be asked of cells, but in most cases we do not know the answers. How much of cellular organization is dictated by global cell polarity cues as opposed to local interactions between cellular components? Does cellular structure persist across cell generations? What is the relationship between cell geometry and tissue organization? What ensures that intracellular structures are scaled to the overall size of the cell? Cell biology is only now beginning to come to grips with these questions. PMID:21880160

Heterogeneous Structure of Stem Cells Dynamics: Statistical Models and Quantitative Predictions

PubMed Central

Bogdan, Paul; Deasy, Bridget M.; Gharaibeh, Burhan; Roehrs, Timo; Marculescu, Radu

2014-01-01

Understanding stem cell (SC) population dynamics is essential for developing models that can be used in basic science and medicine, to aid in predicting cells fate. These models can be used as tools e.g. in studying patho-physiological events at the cellular and tissue level, predicting (mal)functions along the developmental course, and personalized regenerative medicine. Using time-lapsed imaging and statistical tools, we show that the dynamics of SC populations involve a heterogeneous structure consisting of multiple sub-population behaviors. Using non-Gaussian statistical approaches, we identify the co-existence of fast and slow dividing subpopulations, and quiescent cells, in stem cells from three species. The mathematical analysis also shows that, instead of developing independently, SCs exhibit a time-dependent fractal behavior as they interact with each other through molecular and tactile signals. These findings suggest that more sophisticated models of SC dynamics should view SC populations as a collective and avoid the simplifying homogeneity assumption by accounting for the presence of more than one dividing sub-population, and their multi-fractal characteristics. PMID:24769917

Importin-β Directly Regulates the Motor Activity and Turnover of a Kinesin-4.

PubMed

Ganguly, Anindya; DeMott, Logan; Zhu, Chuanmei; McClosky, Daniel D; Anderson, Charles T; Dixit, Ram

2018-03-12

Spatiotemporal regulation of kinesins is essential for microtubule-dependent intracellular transport. In plants, cell wall deposition depends on the FRA1 kinesin, whose abundance and motility are tightly controlled to match cellular growth rate. Here, we show that an importin-β, IMB4, regulates FRA1 activity in a developmental manner. IMB4 physically interacts with a PY motif in the FRA1 motor domain and inhibits its motility by preventing microtubule binding, while also protecting FRA1 against proteasome-mediated degradation, thus providing a mechanism to couple the motility and stability of FRA1. This regulatory mechanism is likely to be broadly applicable, based on the conservation of the PY motif in the motor domains of plant and animal kinesins and the direct interaction of multiple plant kinesins with IMB4. Together, our data establish IMB4 as a multi-functional regulator of FRA1 and reveal a mechanism for how plants control the magnitude of cargo transport needed for cell wall assembly. Copyright © 2018 Elsevier Inc. All rights reserved.

RNAi Functions in Adaptive Reprogramming of the Genome | Center for Cancer Research

Cancer.gov

The regulation of transcribing DNA into RNA, including the production, processing, and degradation of RNA transcripts, affects the expression and the regulation of the genome in ways that are just beginning to be unraveled. A surprising discovery in recent years is that the vast majority of the genome is transcribed to yield an abundance of RNA transcripts. Many transcripts are regulated by the exosome, a multi-protein complex that degrades RNAs, and may also be targeted, under certain conditions, by the RNA interference (RNAi) pathway. These RNA degrading activities can recruit factors to silence certain regions of the genome by condensing the DNA into tightly-packed heterochromatin. For some chromosomal regions, such as centromeres and telomeres, which lie at the center and ends of chromosomes, respectively, silencing must be stably enforced through each cell generation. For other regions, silencing mechanisms must be easily reversible to activate gene expression in response to changing environmental or developmental conditions. Thus, the regulation of gene silencing is key to maintaining the integrity of the genome and proper cellular expression patterns, which, when disrupted can underlie many diseases, including cancer.

78 FR 3009 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-15

... Committee: Center for Scientific Review Special Emphasis Panel; Behavioral Neuroscience. Date: February 6... . Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review Group... Panel; Member Conflict: Integrative Functional and Cognitive Neurobiology. Date: February 13-14, 2013...

75 FR 54893 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-09

... 7850, Bethesda, MD 20892. 301-435-3009. [email protected] . Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review Group, Molecular Neuropharmacology and Signaling... . Name of Committee: Emerging Technologies and Training Neurosciences Integrated Review Group, Molecular...

Multi-Modal Traveler Information System - Cellular 911-State of the Practice

DOT National Transportation Integrated Search

1997-05-19

Working paper evaluates the implemented public 911 and private non-911 cellular : based emergency centers around the country, and within the : Gary-Chicago-Milwaukee (GCM) Corridor and documents the impact, implications and : experiences of switching...

Neuronal pathway finding: from neurons to initial neural networks.

PubMed

Roscigno, Cecelia I

2004-10-01

Neuronal pathway finding is crucial for structured cellular organization and development of neural circuits within the nervous system. Neuronal pathway finding within the visual system has been extensively studied and therefore is used as a model to review existing knowledge regarding concepts of this developmental process. General principles of neuron pathway finding throughout the nervous system exist. Comprehension of these concepts guides neuroscience nurses in gaining an understanding of the developmental course of action, the implications of different anomalies, as well as the theoretical basis and nursing implications of some provocative new therapies being proposed to treat neurodegenerative diseases and neurologic injuries. These therapies have limitations in light of current ethical, developmental, and delivery modes and what is known about the development of neuronal pathways.

The Classroom as Living Room: Using Group Support Systems to Promote Student Retention and Cognitive Growth in Adult Developmental Students.

ERIC Educational Resources Information Center

Goldman, Ruth E.

A project is described that was undertaken by the Developmental Studies Department at Wayne Community College (Michigan), an urban multi-campus institution of 25,000 students serving an entire county involving research in the psychology of the new adult learner. The approach used was to systematically build a classroom environment that responded…

A global characterization and identification of multifunctional enzymes.

PubMed

Cheng, Xian-Ying; Huang, Wei-Juan; Hu, Shi-Chang; Zhang, Hai-Lei; Wang, Hao; Zhang, Jing-Xian; Lin, Hong-Huang; Chen, Yu-Zong; Zou, Quan; Ji, Zhi-Liang

2012-01-01

Multi-functional enzymes are enzymes that perform multiple physiological functions. Characterization and identification of multi-functional enzymes are critical for communication and cooperation between different functions and pathways within a complex cellular system or between cells. In present study, we collected literature-reported 6,799 multi-functional enzymes and systematically characterized them in structural, functional, and evolutionary aspects. It was found that four physiochemical properties, that is, charge, polarizability, hydrophobicity, and solvent accessibility, are important for characterization of multi-functional enzymes. Accordingly, a combinational model of support vector machine and random forest model was constructed, based on which 6,956 potential novel multi-functional enzymes were successfully identified from the ENZYME database. Moreover, it was observed that multi-functional enzymes are non-evenly distributed in species, and that Bacteria have relatively more multi-functional enzymes than Archaebacteria and Eukaryota. Comparative analysis indicated that the multi-functional enzymes experienced a fluctuation of gene gain and loss during the evolution from S. cerevisiae to H. sapiens. Further pathway analyses indicated that a majority of multi-functional enzymes were well preserved in catalyzing several essential cellular processes, for example, metabolisms of carbohydrates, nucleotides, and amino acids. What's more, a database of known multi-functional enzymes and a server for novel multi-functional enzyme prediction were also constructed for free access at http://bioinf.xmu.edu.cn/databases/MFEs/index.htm.

ETOILE Regulates Developmental Patterning in the Filamentous Brown Alga Ectocarpus siliculosus[W

PubMed Central

Le Bail, Aude; Billoud, Bernard; Le Panse, Sophie; Chenivesse, Sabine; Charrier, Bénédicte

2011-01-01

Brown algae are multicellular marine organisms evolutionarily distant from both metazoans and land plants. The molecular or cellular mechanisms that govern the developmental patterning in brown algae are poorly characterized. Here, we report the first morphogenetic mutant, étoile (etl), produced in the brown algal model Ectocarpus siliculosus. Genetic, cellular, and morphometric analyses showed that a single recessive locus, ETL, regulates cell differentiation: etl cells display thickening of the extracellular matrix (ECM), and the elongated, apical, and actively dividing E cells are underrepresented. As a result of this defect, the overrepresentation of round, branch-initiating R cells in the etl mutant leads to the rapid induction of the branching process at the expense of the uniaxial growth in the primary filament. Computational modeling allowed the simulation of the etl mutant phenotype by including a modified response to the neighborhood information in the division rules used to specify wild-type development. Microarray experiments supported the hypothesis of a defect in cell–cell communication, as primarily Lin-Notch-domain transmembrane proteins, which share similarities with metazoan Notch proteins involved in binary cell differentiation were repressed in etl. Thus, our study highlights the role of the ECM and of novel transmembrane proteins in cell–cell communication during the establishment of the developmental pattern in this brown alga. PMID:21478443

76 FR 54238 - Center for Scientific Review; Notice of Closed Meetings

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2011-08-31

...-806-2515, [email protected] . Name of Committee: Molecular, Cellular and Developmental Neuroscience... Neuroscience Integrated Review Group, Neurogenesis and Cell Fate Study Section. Date: October 5, 2011. Time: 8... Cognitive Neuroscience Integrated Review Group, Neuroendocrinology, Neuroimmunology, Rhythms and Sleep Study...

76 FR 3640 - Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-20

...-1747. [email protected] . Name of Committee: Integrative, Functional and Cognitive Neuroscience...: Integrative Neuroscience. Date: February 17-18, 2011. Time: 7 a.m. to 8 p.m. Agenda: To review and evaluate...: Molecular, Cellular and Developmental Neuroscience Integrated Review Group. Biophysics of Neural Systems...

77 FR 3277 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-23

... Training Neurosciences Integrated Review Group; Molecular Neurogenetics Study Section. Date: February 16-17..., [email protected] . Name of Committee: Vascular and Hematology Integrated Review Group; Molecular and...- 1213, [email protected] . Name of Committee: Molecular, Cellular and Developmental Neuroscience...

20180312 - Mechanistic Modeling of Developmental Defects through Computational Embryology (SOT)

EPA Science Inventory

Significant advances in the genome sciences, in automated high-throughput screening (HTS), and in alternative methods for testing enable rapid profiling of chemical libraries for quantitative effects on diverse cellular activities. While a surfeit of HTS data and information is n...

Expanding the test set: Chemicals with potential to disrupt mammalian brain development

EPA Science Inventory

High-throughput test methods including molecular, cellular, and alternative species-based assays that examine critical events of normal brain development are being developed for detection of developmental neurotoxcants. As new assays are developed, a "training set' of chemicals i...

High-throughput screening, predictive modeling and computational embryology - Abstract

EPA Science Inventory

High-throughput screening (HTS) studies are providing a rich source of data that can be applied to chemical profiling to address sensitivity and specificity of molecular targets, biological pathways, cellular and developmental processes. EPA’s ToxCast project is testing 960 uniq...

ADHESION AND REPULSION MOLECULES IN DEVELOPMENTAL NEUROTOXIC INJURY

EPA Science Inventory

Work during the next year will focus on establishing structural and functional correlations between the changes in Eph/ephrin expression and MeHg exposure. We have begun to characterize the cellular expression of the specific molecules using in situ hybridization ...

Changes in lipid membranes may trigger amyloid toxicity in Alzheimer's disease

PubMed Central

Drolle, Elizabeth; Negoda, Alexander; Hammond, Keely; Pavlov, Evgeny

2017-01-01

Amyloid-beta peptides (Aβ), implicated in Alzheimer’s disease (AD), interact with the cellular membrane and induce amyloid toxicity. The composition of cellular membranes changes in aging and AD. We designed multi-component lipid models to mimic healthy and diseased states of the neuronal membrane. Using atomic force microscopy (AFM), Kelvin probe force microscopy (KPFM) and black lipid membrane (BLM) techniques, we demonstrated that these model membranes differ in their nanoscale structure and physical properties, and interact differently with Aβ1–42. Based on our data, we propose a new hypothesis that changes in lipid membrane due to aging and AD may trigger amyloid toxicity through electrostatic mechanisms, similar to the accepted mechanism of antimicrobial peptide action. Understanding the role of the membrane changes as a key activating amyloid toxicity may aid in the development of a new avenue for the prevention and treatment of AD. PMID:28767712

Recent Advances in Subunit Vaccine Carriers

PubMed Central

Vartak, Abhishek; Sucheck, Steven J.

2016-01-01

The lower immunogenicity of synthetic subunit antigens, compared to live attenuated vaccines, is being addressed with improved vaccine carriers. Recent reports indicate that the physio-chemical properties of these carriers can be altered to achieve optimal antigen presentation, endosomal escape, particle bio-distribution, and cellular trafficking. The carriers can be modified with various antigens and ligands for dendritic cells targeting. They can also be modified with adjuvants, either covalently or entrapped in the matrix, to improve cellular and humoral immune responses against the antigen. As a result, these multi-functional carrier systems are being explored for use in active immunotherapy against cancer and infectious diseases. Advancing technology, improved analytical methods, and use of computational methodology have also contributed to the development of subunit vaccine carriers. This review details recent breakthroughs in the design of nano-particulate vaccine carriers, including liposomes, polymeric nanoparticles, and inorganic nanoparticles. PMID:27104575

Smart-Pixel Array Processors Based on Optimal Cellular Neural Networks for Space Sensor Applications

NASA Technical Reports Server (NTRS)

Fang, Wai-Chi; Sheu, Bing J.; Venus, Holger; Sandau, Rainer

1997-01-01

A smart-pixel cellular neural network (CNN) with hardware annealing capability, digitally programmable synaptic weights, and multisensor parallel interface has been under development for advanced space sensor applications. The smart-pixel CNN architecture is a programmable multi-dimensional array of optoelectronic neurons which are locally connected with their local neurons and associated active-pixel sensors. Integration of the neuroprocessor in each processor node of a scalable multiprocessor system offers orders-of-magnitude computing performance enhancements for on-board real-time intelligent multisensor processing and control tasks of advanced small satellites. The smart-pixel CNN operation theory, architecture, design and implementation, and system applications are investigated in detail. The VLSI (Very Large Scale Integration) implementation feasibility was illustrated by a prototype smart-pixel 5x5 neuroprocessor array chip of active dimensions 1380 micron x 746 micron in a 2-micron CMOS technology.

Wet-spinning fabrication of shear-patterned alginate hydrogel microfibers and the guidance of cell alignment

PubMed Central

Yang, You; Sun, Jing; Liu, Xiaolu; Guo, Zhenzhen; He, Yunhu; Wei, Dan; Zhong, Meiling; Guo, Likun; Zhang, Xingdong

2017-01-01

Abstract Native tissue is naturally comprised of highly-ordered cell-matrix assemblies in a multi-hierarchical way, and the nano/submicron alignment of fibrous matrix is found to be significant in supporting cellular functionalization. In this study, a self-designed wet-spinning device appended with a rotary receiving pool was used to continuously produce shear-patterned hydrogel microfibers with aligned submicron topography. The process that the flow-induced shear force reshapes the surface of hydrogel fiber into aligned submicron topography was systematically analysed. Afterwards, the effect of fiber topography on cellular longitudinal spread and elongation was investigated by culturing rat neuron-like PC12 cells and human osteosarcoma MG63 cells with the spun hydrogel microfibers, respectively. The results suggested that the stronger shear flow force would lead to more distinct aligned submicron topography on fiber surface, which could induce cell orientation along with fiber axis and therefore form the cell-matrix dual-alignment. Finally, a multi-hierarchical tissue-like structure constructed by dual-oriented cell-matrix assemblies was fabricated based on this wet-spinning method. This work is believed to be a potentially novel biofabrication scheme for bottom-up constructing of engineered linear tissue, such as nerve bundle, cortical bone, muscle and hepatic cord. PMID:29026644

Update on Development of Mesh Generation Algorithms in MeshKit

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

Jain, Rajeev; Vanderzee, Evan; Mahadevan, Vijay

2015-09-30

MeshKit uses a graph-based design for coding all its meshing algorithms, which includes the Reactor Geometry (and mesh) Generation (RGG) algorithms. This report highlights the developmental updates of all the algorithms, results and future work. Parallel versions of algorithms, documentation and performance results are reported. RGG GUI design was updated to incorporate new features requested by the users; boundary layer generation and parallel RGG support were added to the GUI. Key contributions to the release, upgrade and maintenance of other SIGMA1 libraries (CGM and MOAB) were made. Several fundamental meshing algorithms for creating a robust parallel meshing pipeline in MeshKitmore » are under development. Results and current status of automated, open-source and high quality nuclear reactor assembly mesh generation algorithms such as trimesher, quadmesher, interval matching and multi-sweeper are reported.« less

Developmentally Appropriate Practices in the Primary Program: A Survey of Primary School Teachers.

ERIC Educational Resources Information Center

Addington, Brenda Burton; Hinton, Samuel

Under the Kentucky Education Reform Act, public schools in Kentucky were required to restructure the traditional kindergarten through third-grade classes into a multi-age and multi-ability level, ungraded primary program during the 1993-1994 school year. Classrooms that once contained children at relatively the same age have been replaced with…

The Development of Stranger Fear in Infancy and Toddlerhood: Normative Development, Individual Differences, Antecedents, and Outcomes

ERIC Educational Resources Information Center

Brooker, Rebecca J.; Buss, Kristin A.; Lemery-Chalfant, Kathryn; Aksan, Nazan; Davidson, Richard J.; Goldsmith, H. Hill

2013-01-01

Despite implications that stranger fear is an important aspect of developing behavioral inhibition, a known risk factor for anxiety, normative and atypical developmental trajectories of stranger fear across infancy and toddlerhood remain understudied. We used a large, longitudinal data set (N = 1285) including multi-trait, multi-method assessments…

Chitosan-folate decorated carbon nanotubes for site specific lung cancer delivery.

PubMed

Singh, Rahul Pratap; Sharma, Gunjan; Sonali; Singh, Sanjay; Bharti, Shreekant; Pandey, Bajarangprasad L; Koch, Biplob; Muthu, Madaswamy S

2017-08-01

The aim of this work was to formulate chitosan-folate conjugated multi-walled carbon nanotubes for the lung cancer targeted delivery of docetaxel. The chitosan-folate conjugate was synthesized and the conjugation was confirmed by Fourier transform infrared spectroscopy. The multi-walled carbon nanotubes were characterized for their particle size, polydispersity, zeta potential, surface morphology, drug encapsulation efficiency and in vitro release study. The in vitro cellular uptake, cytotoxicity, and cell cycle analysis of the docetaxel/coumarin-6 loaded multi-walled carbon nanotubes were carried out to compare the effectiveness of the formulations. The biocompatibility and safety of chitosan-folate conjugated multi-walled carbon nanotubes was analyzed by lung histopathology in comparison with marketed docetaxel formulation (Docel™) and acylated multi-walled carbon nanotubes. The cellular internalization study shown that the chitosan-folate conjugated multi-walled carbon nanotubes could be easily internalized into the lung cancer cells through a folate receptor-mediated endocytic pathway. The IC 50 values exhibited that chitosan-folate conjugated multi-walled carbon nanotubes could be 89-fold more effective than Docel™ in human lung cancer cells (A549 cells). Copyright © 2017 Elsevier B.V. All rights reserved.

DNA replication stress: from molecular mechanisms to human disease.

PubMed

Muñoz, Sergio; Méndez, Juan

2017-02-01

The genome of proliferating cells must be precisely duplicated in each cell division cycle. Chromosomal replication entails risks such as the possibility of introducing breaks and/or mutations in the genome. Hence, DNA replication requires the coordinated action of multiple proteins and regulatory factors, whose deregulation causes severe developmental diseases and predisposes to cancer. In recent years, the concept of "replicative stress" (RS) has attracted much attention as it impinges directly on genomic stability and offers a promising new avenue to design anticancer therapies. In this review, we summarize recent progress in three areas: (1) endogenous and exogenous factors that contribute to RS, (2) molecular mechanisms that mediate the cellular responses to RS, and (3) the large list of diseases that are directly or indirectly linked to RS.

45 CFR 1386.20 - Designated State Protection and Advocacy agency.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON DEVELOPMENTAL DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM FORMULA GRANT PROGRAMS State System for Protection and Advocacy of the Rights of Individuals with Developmental Disabilities § 1386.20 Designated State Protection...

Developmental Exposure to A Commercial PBDE Mixture: Effects on Protein Networks in the Cerebellum and Hippocampus of Rats

EPA Science Inventory

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are structurally similar topolychlorinated biphenyls (PCBs) and have both central (learning and memory deficits) and peripheral (motor dysfunction) neurotoxic effects at concentrations/doses similar to those of PCBs. The cellular...

75 FR 1397 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-11

... personal privacy. Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review Group; Molecular Neuropharmacology and Signaling Study Section. Date: February 4-5, 2010. Time: 8 a.m....gov . Name of Committee: Genes, Genomes, and Genetics Integrated Review Group; Prokaryotic Cell and...

Validity and Reliability of the "Behavior Problems Inventory," the "Aberrant Behavior Checklist," and the "Repetitive Behavior Scale--Revised" among Infants and Toddlers at Risk for Intellectual or Developmental Disabilities: A Multi-Method Assessment Approach

ERIC Educational Resources Information Center

Rojahn, Johannes; Schroeder, Stephen R.; Mayo-Ortega, Liliana; Oyama-Ganiko, Rosao; LeBlanc, Judith; Marquis, Janet; Berke, Elizabeth

2013-01-01

Reliable and valid assessment of aberrant behaviors is essential in empirically verifying prevention and intervention for individuals with intellectual or developmental disabilities (IDD). Few instruments exist which assess behavior problems in infants. The current longitudinal study examined the performance of three behavior-rating scales for…

The telomeric protein SNM1B/Apollo is required for normal cell proliferation and embryonic development

PubMed Central

Akhter, Shamima; Lam, Yung C.; Chang, Sandy; Legerski, Randy J.

2013-01-01

Summary Conserved metallo β-Lactamase and β-CASP (CPSF-Artemis-Snm1-Pso2) domain nuclease family member SNM1B/Apollo is a shelterin-associated protein that localizes to telomeres through its interaction with TRF2. To study its in vivo role, we generated a knockout of SNM1B/Apollo in a mouse model. Snm1B/Apollo homozygous null mice die at birth with developmental delay and defects in multiple organ systems. Cell proliferation defects were observed in Snm1B/Apollo mutant mouse embryonic fibroblasts (MEFs) owing to high levels of telomeric end-to-end fusions. Deficiency of the nonhomologous end-joining (NHEJ) factor Ku70, but not p53, rescued the developmental defects and lethality observed in Snm1B/Apollo mutant mice as well as the impaired proliferation of Snm1B/Apollo-deficient MEFs. These findings demonstrate that SNM1B/Apollo is required to protect telomeres against NHEJ-mediated repair, which results in genomic instability and the consequent multi-organ developmental failure. Although Snm1B/Apollo-deficient MEFs exhibited high levels of apoptosis, abrogation of p53-dependent programmed cell death did not rescue the multi-organ developmental failure in the mice. PMID:20854421

The Bicoid Class Homeodomain Factors ceh-36/OTX and unc-30/PITX Cooperate in C. elegans Embryonic Progenitor Cells to Regulate Robust Development

PubMed Central

Walton, Travis; Preston, Elicia; Nair, Gautham; Zacharias, Amanda L.; Raj, Arjun; Murray, John Isaac

2015-01-01

While many transcriptional regulators of pluripotent and terminally differentiated states have been identified, regulation of intermediate progenitor states is less well understood. Previous high throughput cellular resolution expression studies identified dozens of transcription factors with lineage-specific expression patterns in C. elegans embryos that could regulate progenitor identity. In this study we identified a broad embryonic role for the C. elegans OTX transcription factor ceh-36, which was previously shown to be required for the terminal specification of four neurons. ceh-36 is expressed in progenitors of over 30% of embryonic cells, yet is not required for embryonic viability. Quantitative phenotyping by computational analysis of time-lapse movies of ceh-36 mutant embryos identified cell cycle or cell migration defects in over 100 of these cells, but most defects were low-penetrance, suggesting redundancy. Expression of ceh-36 partially overlaps with that of the PITX transcription factor unc-30. unc-30 single mutants are viable but loss of both ceh-36 and unc-30 causes 100% lethality, and double mutants have significantly higher frequencies of cellular developmental defects in the cells where their expression normally overlaps. These factors are also required for robust expression of the downstream developmental regulator mls-2/HMX. This work provides the first example of genetic redundancy between the related yet evolutionarily distant OTX and PITX families of bicoid class homeodomain factors and demonstrates the power of quantitative developmental phenotyping in C. elegans to identify developmental regulators acting in progenitor cells. PMID:25738873

Developmentally arrested structures preceding cerebellar tumors in von Hippel–Lindau disease

PubMed Central

Shively, Sharon B; Falke, Eric A; Li, Jie; Tran, Maxine G B; Thompson, Eli R; Maxwell, Patrick H; Roessler, Erich; Oldfield, Edward H; Lonser, Russell R; Vortmeyer, Alexander O

2011-01-01

There is increasing evidence that suggests that knockout of tumor-suppressor gene function causes developmental arrest and protraction of cellular differentiation. In the peripheral nervous system of patients with the tumor-suppressor gene disorder, von Hippel–Lindau disease, we have demonstrated developmentally arrested structural elements composed of hemangioblast progenitor cells. Some developmentally arrested structural elements progress to a frank tumor, hemangioblastoma. However, in von Hippel–Lindau disease, hemangioblastomas are frequently observed in the cerebellum, suggesting an origin in the central nervous system. We performed a structural and topographic analysis of cerebellar tissues obtained from von Hippel–Lindau disease patients to identify and characterize developmentally arrested structural elements in the central nervous system. We examined the entire cerebella of five tumor-free von Hippel–Lindau disease patients and of three non-von Hippel–Lindau disease controls. In all, 9 cerebellar developmentally arrested structural elements were detected and topographically mapped in 385 blocks of von Hippel–Lindau disease cerebella. No developmentally arrested structural elements were seen in 214 blocks from control cerebella. Developmentally arrested structural elements are composed of poorly differentiated cells that express hypoxia-inducible factor (HIF)2α, but not HIF1α or brachyury, and preferentially involve the molecular layer of the dorsum cerebelli. For the first time, we identify and characterize developmentally arrested structural elements in the central nervous system of von Hippel–Lindau patients. We provide evidence that developmentally arrested structural elements in the cerebellum are composed of developmentally arrested hemangioblast progenitor cells in the molecular layer of the dorsum cerebelli. PMID:21499240

Comprehensive comparative analysis and identification of RNA-binding protein domains: multi-class classification and feature selection.

PubMed

Jahandideh, Samad; Srinivasasainagendra, Vinodh; Zhi, Degui

2012-11-07

RNA-protein interaction plays an important role in various cellular processes, such as protein synthesis, gene regulation, post-transcriptional gene regulation, alternative splicing, and infections by RNA viruses. In this study, using Gene Ontology Annotated (GOA) and Structural Classification of Proteins (SCOP) databases an automatic procedure was designed to capture structurally solved RNA-binding protein domains in different subclasses. Subsequently, we applied tuned multi-class SVM (TMCSVM), Random Forest (RF), and multi-class ℓ1/ℓq-regularized logistic regression (MCRLR) for analysis and classifying RNA-binding protein domains based on a comprehensive set of sequence and structural features. In this study, we compared prediction accuracy of three different state-of-the-art predictor methods. From our results, TMCSVM outperforms the other methods and suggests the potential of TMCSVM as a useful tool for facilitating the multi-class prediction of RNA-binding protein domains. On the other hand, MCRLR by elucidating importance of features for their contribution in predictive accuracy of RNA-binding protein domains subclasses, helps us to provide some biological insights into the roles of sequences and structures in protein-RNA interactions.

Multi-stability and variable stiffness of cellular solids designed based on origami patterns

NASA Astrophysics Data System (ADS)

Sengupta, Sattam; Li, Suyi

2017-04-01

The application of origami-inspired designs to engineered structures and materials has been a subject of much research efforts. These structures and materials, whose mechanical properties are directly related to the geometry of folding, are capable of achieving a host of unique adaptive functions. In this study, we investigate a three-dimensional multistability and variable stiffness function of a cellular solid based on the Miura-Ori folding pattern. The unit cell of such a solid, consisting of two stacked Miura-Ori sheets, can be elastically bistable due to the nonlinear relationship between rigid-folding deformation and crease material bending. Such a bistability possesses an unorthodox property: the critical, unstable configuration lies on the same side of two stable ones, so that two different force-deformation curves co-exist within the same range of deformation. By exploiting such unique stability properties, we can achieve a programmable stiffness change between the two elastically stable states, and the stiffness differences can be prescribed by tailoring the crease patterns of the cell. This paper presents a comprehensive parametric study revealing the correlations between such variable stiffness and various design parameters. The unique properties stemming from the bistability and design of such a unit cell can be advanced further by assembling them into a solid which can be capable of shape morphing and programmable mechanical properties.

Stiffness and strength of fiber reinforced polymer composite bridge deck systems

NASA Astrophysics Data System (ADS)

Zhou, Aixi

This research investigates two principal characteristics that are of primary importance in Fiber Reinforced Polymer (FRP) bridge deck applications: STIFFNESS and STRENGTH. The research was undertaken by investigating the stiffness and strength characteristics of the multi-cellular FRP bridge deck systems consisting of pultruded FRP shapes. A systematic analysis procedure was developed for the stiffness analysis of multi-cellular FRP deck systems. This procedure uses the Method of Elastic Equivalence to model the cellular deck as an equivalent orthotropic plate. The procedure provides a practical method to predict the equivalent orthotropic plate properties of cellular FRP decks. Analytical solutions for the bending analysis of single span decks were developed using classical laminated plate theory. The analysis procedures can be extended to analyze continuous FRP decks. It can also be further developed using higher order plate theories. Several failure modes of the cellular FRP deck systems were recorded and analyzed through laboratory and field tests and Finite Element Analysis (FEA). Two schemes of loading patches were used in the laboratory test: a steel patch made according to the ASSHTO's bridge testing specifications; and a tire patch made from a real truck tire reinforced with silicon rubber. The tire patch was specially designed to simulate service loading conditions by modifying real contact loading from a tire. Our research shows that the effects of the stiffness and contact conditions of loading patches are significant in the stiffness and strength testing of FRP decks. Due to the localization of load, a simulated tire patch yields larger deflection than the steel patch under the same loading level. The tire patch produces significantly different failure compared to the steel patch: a local bending mode with less damage for the tire patch; and a local punching-shear mode for the steel patch. A deck failure function method is proposed for predicting the failure of FRP decks. Using developed laminated composite theories and FEA techniques, a strength analysis procedure containing ply-level information was proposed and detailed for FRP deck systems. The behavior of the deck's unsupported (free) edges was also investigated using ply-level FEA.

Hematopoiesis: an evolving paradigm for stem cell biology.

PubMed

Orkin, Stuart H; Zon, Leonard I

2008-02-22

Establishment and maintenance of the blood system relies on self-renewing hematopoietic stem cells (HSCs) that normally reside in small numbers in the bone marrow niche of adult mammals. This Review describes the developmental origins of HSCs and the molecular mechanisms that regulate lineage-specific differentiation. Studies of hematopoiesis provide critical insights of general relevance to other areas of stem cell biology including the role of cellular interactions in development and tissue homeostasis, lineage programming and reprogramming by transcription factors, and stage- and age-specific differences in cellular phenotypes.

Strengthening Data Confidentiality and Integrity Protection in the Context of a Multi-Centric Information System Dedicated to Autism Spectrum Disorder.

PubMed

Ben Said, Mohamed; Robel, Laurence; Golse, Bernard; Jais, Jean Philippe

2017-01-01

Autism spectrum disorders (ASD) are complex neuro-developmental disorders affecting children in early age. Diagnosis relies on multidisciplinary investigations, in psychiatry, neurology, genetics, electrophysiology, neuro-imagery, audiology, and ophthalmology. To support clinicians, researchers, and public health decision makers, we developed an information system dedicated to ASD, called TEDIS. It was designed to manage systematic, exhaustive and continuous multi-centric patient data collection via secured internet connections. TEDIS will be deployed in nine ASD expert assessment centers in Ile-DeFrance district. We present security policy and infrastructure developed in context of TEDIS to protect patient privacy and clinical information. TEDIS security policy was organized around governance, ethical and organisational chart-agreement, patients consents, controlled user access, patients' privacy protection, constrained patients' data access. Security infrastructure was enriched by further technical solutions to reinforce ASD patients' privacy protection. Solutions were tested on local secured intranet environment and showed fluid functionality with consistent, transparent and safe encrypting-decrypting results.

Mathematical modelling in developmental biology.

PubMed

Vasieva, Olga; Rasolonjanahary, Manan'Iarivo; Vasiev, Bakhtier

2013-06-01

In recent decades, molecular and cellular biology has benefited from numerous fascinating developments in experimental technique, generating an overwhelming amount of data on various biological objects and processes. This, in turn, has led biologists to look for appropriate tools to facilitate systematic analysis of data. Thus, the need for mathematical techniques, which can be used to aid the classification and understanding of this ever-growing body of experimental data, is more profound now than ever before. Mathematical modelling is becoming increasingly integrated into biological studies in general and into developmental biology particularly. This review outlines some achievements of mathematics as applied to developmental biology and demonstrates the mathematical formulation of basic principles driving morphogenesis. We begin by describing a mathematical formalism used to analyse the formation and scaling of morphogen gradients. Then we address a problem of interplay between the dynamics of morphogen gradients and movement of cells, referring to mathematical models of gastrulation in the chick embryo. In the last section, we give an overview of various mathematical models used in the study of the developmental cycle of Dictyostelium discoideum, which is probably the best example of successful mathematical modelling in developmental biology.

Demographic profile of families and children in the Study to Explore Early Development (SEED): Case-control study of autism spectrum disorder

PubMed Central

DiGuiseppi, Carolyn G.; Daniels, Julie L.; Fallin, Daniele M.; Rosenberg, Steven A.; Schieve, Laura A.; Thomas, Kathleen C.; Windham, Gayle C.; Goss, Cynthia W.; Soke, Gnakub N.; Currie, Dustin W.; Singer, Alison B.; Lee, Li-Ching; Bernal, Pilar; Croen, Lisa A.; Miller, Lisa A.; Pinto-Martin, Jennifer A.; Young, Lisa M.; Schendel, Diana E.

2016-01-01

Background The Study to Explore Early Development (SEED) is designed to enhance knowledge of autism spectrum disorder characteristics and etiologies. Objective This paper describes the demographic profile of enrolled families and examines sociodemographic differences between children with autism spectrum disorder and children with other developmental problems or who are typically developing. Methods This multi-site case-control study used health, education, and birth certificate records to identify and enroll children aged 2–5 years into one of three groups: 1) cases (children with autism spectrum disorder), 2) developmental delay or disorder controls, or 3) general population controls. Study group classification was based on sampling source, prior diagnoses, and study screening tests and developmental evaluations. The child's primary caregiver provided demographic characteristics through a telephone (or occasionally face-to-face) interview. Groups were compared using ANOVA, chi-squared test, or multinomial logistic regression as appropriate. Results Of 2768 study children, sizeable proportions were born to mothers of non-White race (31.7%), Hispanic ethnicity (11.4%), and foreign birth (17.6%); 33.0% of households had incomes below the US median. The autism spectrum disorder and population control groups differed significantly on nearly all sociodemographic parameters. In contrast, the autism spectrum disorder and developmental delay or disorder groups had generally similar sociodemographic characteristics. Conclusions SEED enrolled a sociodemographically diverse sample, which will allow further, in-depth exploration of sociodemographic differences between study groups and provide novel opportunities to explore sociodemographic influences on etiologic risk factor associations with autism spectrum disorder and phenotypic subtypes. PMID:26917104

Demographic profile of families and children in the Study to Explore Early Development (SEED): Case-control study of autism spectrum disorder.

PubMed

DiGuiseppi, Carolyn G; Daniels, Julie L; Fallin, Daniele M; Rosenberg, Steven A; Schieve, Laura A; Thomas, Kathleen C; Windham, Gayle C; Goss, Cynthia W; Soke, Gnakub N; Currie, Dustin W; Singer, Alison B; Lee, Li-Ching; Bernal, Pilar; Croen, Lisa A; Miller, Lisa A; Pinto-Martin, Jennifer A; Young, Lisa M; Schendel, Diana E

2016-07-01

The Study to Explore Early Development (SEED) is designed to enhance knowledge of autism spectrum disorder characteristics and etiologies. This paper describes the demographic profile of enrolled families and examines sociodemographic differences between children with autism spectrum disorder and children with other developmental problems or who are typically developing. This multi-site case-control study used health, education, and birth certificate records to identify and enroll children aged 2-5 years into one of three groups: 1) cases (children with autism spectrum disorder), 2) developmental delay or disorder controls, or 3) general population controls. Study group classification was based on sampling source, prior diagnoses, and study screening tests and developmental evaluations. The child's primary caregiver provided demographic characteristics through a telephone (or occasionally face-to-face) interview. Groups were compared using ANOVA, chi-squared test, or multinomial logistic regression as appropriate. Of 2768 study children, sizeable proportions were born to mothers of non-White race (31.7%), Hispanic ethnicity (11.4%), and foreign birth (17.6%); 33.0% of households had incomes below the US median. The autism spectrum disorder and population control groups differed significantly on nearly all sociodemographic parameters. In contrast, the autism spectrum disorder and developmental delay or disorder groups had generally similar sociodemographic characteristics. SEED enrolled a sociodemographically diverse sample, which will allow further, in-depth exploration of sociodemographic differences between study groups and provide novel opportunities to explore sociodemographic influences on etiologic risk factor associations with autism spectrum disorder and phenotypic subtypes. Copyright © 2016 Elsevier Inc. All rights reserved.

Determination of intra-axial brain tumors cellularity through the analysis of T2 Relaxation time of brain tumors before surgery using MATLAB software.

PubMed

Abdolmohammadi, Jamil; Shafiee, Mohsen; Faeghi, Fariborz; Arefan, Douman; Zali, Alireza; Motiei-Langroudi, Rouzbeh; Farshidfar, Zahra; Nazarlou, Ali Kiani; Tavakkoli, Ali; Yarham, Mohammad

2016-08-01

Timely diagnosis of brain tumors could considerably affect the process of patient treatment. To do so, para-clinical methods, particularly MRI, cannot be ignored. MRI has so far answered significant questions regarding tumor characteristics, as well as helping neurosurgeons. In order to detect the tumor cellularity, neuro-surgeons currently have to sample specimens by biopsy and then send them to the pathology unit. The aim of this study is to determine the tumor cellularity in the brain. In this cross-sectional study, 32 patients (18 males and 14 females from 18-77 y/o) were admitted to the neurosurgery department of Shohada-E Tajrish Hospital in Tehran, Iran from April 2012 to February 2014. In addition to routine pulse sequences, T2W Multi echo pulse sequences were taken and the images were analyzed using the MATLAB software to determine the brain tumor cellularity, compared with the biopsy. These findings illustrate the need for more T2 relaxation time decreases, the higher classes of tumors will stand out in the designed table. In this study, the results show T2 relaxation time with a 85% diagnostic weight, compared with the biopsy, to determine the brain tumor cellularity (p<0.05). Our results indicate that the T2 relaxation time feature is the best method to distinguish and present the degree of intra-axial brain tumors cellularity (85% accuracy compared to biopsy). The use of more data is recommended in order to increase the percent accuracy of this techniques.

Multi-Step Usage of in Vivo Models During Rational Drug Design and Discovery

PubMed Central

Williams, Charles H.; Hong, Charles C.

2011-01-01

In this article we propose a systematic development method for rational drug design while reviewing paradigms in industry, emerging techniques and technologies in the field. Although the process of drug development today has been accelerated by emergence of computational methodologies, it is a herculean challenge requiring exorbitant resources; and often fails to yield clinically viable results. The current paradigm of target based drug design is often misguided and tends to yield compounds that have poor absorption, distribution, metabolism, and excretion, toxicology (ADMET) properties. Therefore, an in vivo organism based approach allowing for a multidisciplinary inquiry into potent and selective molecules is an excellent place to begin rational drug design. We will review how organisms like the zebrafish and Caenorhabditis elegans can not only be starting points, but can be used at various steps of the drug development process from target identification to pre-clinical trial models. This systems biology based approach paired with the power of computational biology; genetics and developmental biology provide a methodological framework to avoid the pitfalls of traditional target based drug design. PMID:21731440

Developmental validation of the PowerPlex(®) Fusion 6C System.

PubMed

Ensenberger, Martin G; Lenz, Kristy A; Matthies, Learden K; Hadinoto, Gregory M; Schienman, John E; Przech, Angela J; Morganti, Michael W; Renstrom, Daniel T; Baker, Victoria M; Gawrys, Kori M; Hoogendoorn, Marlijn; Steffen, Carolyn R; Martín, Pablo; Alonso, Antonio; Olson, Hope R; Sprecher, Cynthia J; Storts, Douglas R

2016-03-01

The PowerPlex(®) Fusion 6C System is a 27-locus, six-dye, multiplex that includes all markers in the expanded CODIS core loci and increases overlap with STR database standards throughout the world. Additionally, it contains two, rapidly mutating, Y-STRs and is capable of both casework and database workflows, including direct amplification. A multi-laboratory developmental validation study was performed on the PowerPlex(®) Fusion 6C System. Here, we report the results of that study which followed SWGDAM guidelines and includes data for: species specificity, sensitivity, stability, precision, reproducibility and repeatability, case-type samples, concordance, stutter, DNA mixtures, and PCR-based procedures. Where appropriate we report data from both extracted DNA samples and direct amplification samples from various substrates and collection devices. Samples from all studies were separated on both Applied Biosystems 3500 series and 6-dye capable 3130 series Genetic Analyzers and data is reported for each. Together, the data validate the design and demonstrate the performance of the PowerPlex(®) Fusion 6C System. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Hyperthermal Environments Simulator for Nuclear Rocket Engine Development

NASA Technical Reports Server (NTRS)

Litchford, Ron J.; Foote, John P.; Clifton, W. B.; Hickman, Robert R.; Wang, Ten-See; Dobson, Christopher C.

2011-01-01

An arc-heater driven hyperthermal convective environments simulator was recently developed and commissioned for long duration hot hydrogen exposure of nuclear thermal rocket materials. This newly established non-nuclear testing capability uses a high-power, multi-gas, wall-stabilized constricted arc-heater to produce hightemperature pressurized hydrogen flows representative of nuclear reactor core environments, excepting radiation effects, and is intended to serve as a low-cost facility for supporting non-nuclear developmental testing of hightemperature fissile fuels and structural materials. The resulting reactor environments simulator represents a valuable addition to the available inventory of non-nuclear test facilities and is uniquely capable of investigating and characterizing candidate fuel/structural materials, improving associated processing/fabrication techniques, and simulating reactor thermal hydraulics. This paper summarizes facility design and engineering development efforts and reports baseline operational characteristics as determined from a series of performance mapping and long duration capability demonstration tests. Potential follow-on developmental strategies are also suggested in view of the technical and policy challenges ahead. Keywords: Nuclear Rocket Engine, Reactor Environments, Non-Nuclear Testing, Fissile Fuel Development.

Developmental thyroid hormone insufficiency and brain development: A role for brain-derived neurotrophic factor (BDNF)?*

EPA Science Inventory

Thyroid hormones (TH) are essential for normal brain development. Even subclinical hypothyroidism experienced in utero can result in neuropsychological deficits in children despite normal thyroid status at birth. Neurotrophins have been implicated in a host of brain cellular func...

75 FR 56115 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-15

... Processes Integrated Review Group, Biobehavioral Regulation, Learning and Ethology Study Section. Date..., Biobehavioral Regulation, Learning and Ethology. Date: October 8, 2010. Time: 9 a.m. to 10 a.m. Agenda: To..., Cellular and Developmental Neuroscience Integrated Review Group, Biophysics of Neural Systems Study Section...

The Effects of In Vivo Acute Exposure to Polychlorinatedbiphenyls on Free and Total Thyroxine in Rats

EPA Science Inventory

Hypothyroxinemia in rats has been well documented as a result of either developmental or adult exposure to polychlorinated biphenyls (PCBs). Hypothetical mechanisms for this include induction of hepatic catabolic enzymes and cellular hormone transporters, and/or interference wit...

75 FR 2877 - Center For Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-19

... Group; Molecular Neurogenetics Study Section. Date: February 11, 2010. Time: 7 a.m. to 6 p.m. Agenda: To...- 0902, [email protected] . Name of Committee: Molecular, Cellular and Developmental Neuroscience..., Genomes, and Genetics Integrated Review Group; Genetic Variation and Evolution Study Section. Date...

Multi-Grade Kindergarten Classrooms and Children's Academic Achievement, Executive Function, and Socio-Emotional Development

ERIC Educational Resources Information Center

Ansari, Arya

2017-01-01

Using data from the Early Childhood Longitudinal Study Kindergarten Class of 2010-2011 (ECLS-K: 2011; n = 11,000), this study examined the developmental outcomes of 5-year-old children in multi-grade classrooms (combined pre-kindergarten and kindergarten classrooms serving 3-, 4-, and 5-year-olds) compared with 5-year-olds attending…

Using Case Study Multi-Methods to Investigate Close(r) Collaboration: Course-Based Tutoring and the Directive/Nondirective Instructional Continuum

ERIC Educational Resources Information Center

Corbett, Steven J.

2011-01-01

This essay presents case studies of "course-based tutoring" (CBT) and one-to-one tutorials in two sections of developmental first-year composition (FYC) at a large West Coast research university. The author's study uses a combination of rhetorical and discourse analyses and ethnographic and case study multi-methods to investigate both…

In silico evolution of the hunchback gene indicates redundancy in cis-regulatory organization and spatial gene expression

PubMed Central

Zagrijchuk, Elizaveta A.; Sabirov, Marat A.; Holloway, David M.; Spirov, Alexander V.

2014-01-01

Biological development depends on the coordinated expression of genes in time and space. Developmental genes have extensive cis-regulatory regions which control their expression. These regions are organized in a modular manner, with different modules controlling expression at different times and locations. Both how modularity evolved and what function it serves are open questions. We present a computational model for the cis-regulation of the hunchback (hb) gene in the fruit fly (Drosophila). We simulate evolution (using an evolutionary computation approach from computer science) to find the optimal cis-regulatory arrangements for fitting experimental hb expression patterns. We find that the cis-regulatory region tends to readily evolve modularity. These cis-regulatory modules (CRMs) do not tend to control single spatial domains, but show a multi-CRM/multi-domain correspondence. We find that the CRM-domain correspondence seen in Drosophila evolves with a high probability in our model, supporting the biological relevance of the approach. The partial redundancy resulting from multi-CRM control may confer some biological robustness against corruption of regulatory sequences. The technique developed on hb could readily be applied to other multi-CRM developmental genes. PMID:24712536

Using CellML with OpenCMISS to Simulate Multi-Scale Physiology

PubMed Central

Nickerson, David P.; Ladd, David; Hussan, Jagir R.; Safaei, Soroush; Suresh, Vinod; Hunter, Peter J.; Bradley, Christopher P.

2014-01-01

OpenCMISS is an open-source modeling environment aimed, in particular, at the solution of bioengineering problems. OpenCMISS consists of two main parts: a computational library (OpenCMISS-Iron) and a field manipulation and visualization library (OpenCMISS-Zinc). OpenCMISS is designed for the solution of coupled multi-scale, multi-physics problems in a general-purpose parallel environment. CellML is an XML format designed to encode biophysically based systems of ordinary differential equations and both linear and non-linear algebraic equations. A primary design goal of CellML is to allow mathematical models to be encoded in a modular and reusable format to aid reproducibility and interoperability of modeling studies. In OpenCMISS, we make use of CellML models to enable users to configure various aspects of their multi-scale physiological models. This avoids the need for users to be familiar with the OpenCMISS internal code in order to perform customized computational experiments. Examples of this are: cellular electrophysiology models embedded in tissue electrical propagation models; material constitutive relationships for mechanical growth and deformation simulations; time-varying boundary conditions for various problem domains; and fluid constitutive relationships and lumped-parameter models. In this paper, we provide implementation details describing how CellML models are integrated into multi-scale physiological models in OpenCMISS. The external interface OpenCMISS presents to users is also described, including specific examples exemplifying the extensibility and usability these tools provide the physiological modeling and simulation community. We conclude with some thoughts on future extension of OpenCMISS to make use of other community developed information standards, such as FieldML, SED-ML, and BioSignalML. Plans for the integration of accelerator code (graphical processing unit and field programmable gate array) generated from CellML models is also discussed. PMID:25601911

A cellular star atlas: using astrocytes from human pluripotent stem cells for disease studies

PubMed Central

Krencik, Robert; Ullian, Erik M.

2013-01-01

What roles do astrocytes play in human disease?This question remains unanswered for nearly every human neurological disorder. Yet, because of their abundance and complexity astrocytes can impact neurological function in many ways. The differentiation of human pluripotent stem cells (hPSCs) into neuronal and glial subtypes, including astrocytes, is becoming routine, thus their use as tools for modeling neurodevelopment and disease will provide one important approach to answer this question. When designing experiments, careful consideration must be given to choosing paradigms for differentiation, maturation, and functional analysis of these temporally asynchronous cellular populations in culture. In the case of astrocytes, they display heterogeneous characteristics depending upon species of origin, brain region, developmental stage, environmental factors, and disease states, all of which may render experimental results highly variable. In this review, challenges and future directions are discussed for using hPSC-derived astroglial progenitors and mature astrocytes for neurodevelopmental studies with a focus on exploring human astrocyte effects upon neuronal function. As new technologies emerge to measure the functions of astrocytes in vitro and in vivo, there is also a need for a standardized source of human astrocytes that are most relevant to the diseases of interest. PMID:23503583

Next-generation mammalian genetics toward organism-level systems biology.

PubMed

Susaki, Etsuo A; Ukai, Hideki; Ueda, Hiroki R

2017-01-01

Organism-level systems biology in mammals aims to identify, analyze, control, and design molecular and cellular networks executing various biological functions in mammals. In particular, system-level identification and analysis of molecular and cellular networks can be accelerated by next-generation mammalian genetics. Mammalian genetics without crossing, where all production and phenotyping studies of genome-edited animals are completed within a single generation drastically reduce the time, space, and effort of conducting the systems research. Next-generation mammalian genetics is based on recent technological advancements in genome editing and developmental engineering. The process begins with introduction of double-strand breaks into genomic DNA by using site-specific endonucleases, which results in highly efficient genome editing in mammalian zygotes or embryonic stem cells. By using nuclease-mediated genome editing in zygotes, or ~100% embryonic stem cell-derived mouse technology, whole-body knock-out and knock-in mice can be produced within a single generation. These emerging technologies allow us to produce multiple knock-out or knock-in strains in high-throughput manner. In this review, we discuss the basic concepts and related technologies as well as current challenges and future opportunities for next-generation mammalian genetics in organism-level systems biology.

Single Cell Force Spectroscopy for Quantification of Cellular Adhesion on Surfaces

NASA Astrophysics Data System (ADS)

Christenson, Wayne B.

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

Nutrition and Fitness Curriculum: Designing Instructional Interventions for Children with Developmental Disabilities

ERIC Educational Resources Information Center

Simpson, Cynthia G.; Swicegood, Philip R.; Gaus, Mark D.

2006-01-01

With the recent rise of childhood obesity, teaching children with developmental disabilities about healthful lifestyle choices has important implications for special educators. Designing instructional interventions for children with developmental disabilities in the areas of nutrition and weight management poses challenges to educators, who must…

MicroRNAs and the metabolic hallmarks of aging.

PubMed

Victoria, Berta; Nunez Lopez, Yury O; Masternak, Michal M

2017-11-05

Aging, the natural process of growing older, is characterized by a progressive deterioration of physiological homeostasis at the cellular, tissue, and organismal level. Metabolically, the aging process is characterized by extensive changes in body composition, multi-tissue/multi-organ insulin resistance, and physiological declines in multiple signaling pathways including growth hormone, insulin/insulin-like growth factor 1, and sex steroids regulation. With this review, we intend to consolidate published information about microRNAs that regulate critical metabolic processes relevant to aging. In certain occasions we uncover relationships likely relevant to aging, which has not been directly described before, such as the miR-451/AMPK axis. We have also included a provocative section highlighting the potential role in aging of a new designation of miRNAs, namely fecal miRNAs, recently discovered to regulate intestinal microbiota in mammals. Copyright © 2016. Published by Elsevier B.V.

Advances in multi-scale modeling of solidification and casting processes

NASA Astrophysics Data System (ADS)

Liu, Baicheng; Xu, Qingyan; Jing, Tao; Shen, Houfa; Han, Zhiqiang

2011-04-01

The development of the aviation, energy and automobile industries requires an advanced integrated product/process R&D systems which could optimize the product and the process design as well. Integrated computational materials engineering (ICME) is a promising approach to fulfill this requirement and make the product and process development efficient, economic, and environmentally friendly. Advances in multi-scale modeling of solidification and casting processes, including mathematical models as well as engineering applications are presented in the paper. Dendrite morphology of magnesium and aluminum alloy of solidification process by using phase field and cellular automaton methods, mathematical models of segregation of large steel ingot, and microstructure models of unidirectionally solidified turbine blade casting are studied and discussed. In addition, some engineering case studies, including microstructure simulation of aluminum casting for automobile industry, segregation of large steel ingot for energy industry, and microstructure simulation of unidirectionally solidified turbine blade castings for aviation industry are discussed.

Theoretical study of chromophores for biological sensing: Understanding the mechanism of rhodol based multi-chromophoric systems

NASA Astrophysics Data System (ADS)

Rivera-Jacquez, Hector J.; Masunov, Artëm E.

2018-06-01

Development of two-photon fluorescent probes can aid in visualizing the cellular environment. Multi-chromophore systems display complex manifolds of electronic transitions, enabling their use for optical sensing applications. Time-Dependent Density Functional Theory (TDDFT) methods allow for accurate predictions of the optical properties. These properties are related to the electronic transitions in the molecules, which include two-photon absorption cross-sections. Here we use TDDFT to understand the mechanism of aza-crown based fluorescent probes for metals sensing applications. Our findings suggest changes in local excitation in the rhodol chromophore between unbound form and when bound to the metal analyte. These changes are caused by a charge transfer from the aza-crown group and pyrazol units toward the rhodol unit. Understanding this mechanism leads to an optimized design with higher two-photon excited fluorescence to be used in medical applications.

Theoretical study of chromophores for biological sensing: Understanding the mechanism of rhodol based multi-chromophoric systems.

PubMed

Rivera-Jacquez, Hector J; Masunov, Artëm E

2018-06-05

Development of two-photon fluorescent probes can aid in visualizing the cellular environment. Multi-chromophore systems display complex manifolds of electronic transitions, enabling their use for optical sensing applications. Time-Dependent Density Functional Theory (TDDFT) methods allow for accurate predictions of the optical properties. These properties are related to the electronic transitions in the molecules, which include two-photon absorption cross-sections. Here we use TDDFT to understand the mechanism of aza-crown based fluorescent probes for metals sensing applications. Our findings suggest changes in local excitation in the rhodol chromophore between unbound form and when bound to the metal analyte. These changes are caused by a charge transfer from the aza-crown group and pyrazol units toward the rhodol unit. Understanding this mechanism leads to an optimized design with higher two-photon excited fluorescence to be used in medical applications. Copyright © 2018 Elsevier B.V. All rights reserved.

Terminal addition in a cellular world.

PubMed

Torday, J S; Miller, William B

2018-07-01

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

Inter-cellular forces orchestrate contact inhibition of locomotion.

PubMed

Davis, John R; Luchici, Andrei; Mosis, Fuad; Thackery, James; Salazar, Jesus A; Mao, Yanlan; Dunn, Graham A; Betz, Timo; Miodownik, Mark; Stramer, Brian M

2015-04-09

Contact inhibition of locomotion (CIL) is a multifaceted process that causes many cell types to repel each other upon collision. During development, this seemingly uncoordinated reaction is a critical driver of cellular dispersion within embryonic tissues. Here, we show that Drosophila hemocytes require a precisely orchestrated CIL response for their developmental dispersal. Hemocyte collision and subsequent repulsion involves a stereotyped sequence of kinematic stages that are modulated by global changes in cytoskeletal dynamics. Tracking actin retrograde flow within hemocytes in vivo reveals synchronous reorganization of colliding actin networks through engagement of an inter-cellular adhesion. This inter-cellular actin-clutch leads to a subsequent build-up in lamellar tension, triggering the development of a transient stress fiber, which orchestrates cellular repulsion. Our findings reveal that the physical coupling of the flowing actin networks during CIL acts as a mechanotransducer, allowing cells to haptically sense each other and coordinate their behaviors. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Single-cell topological RNA-Seq analysis reveals insights into cellular differentiation and development

PubMed Central

Rizvi, Abbas H.; Camara, Pablo G.; Kandror, Elena K.; Roberts, Thomas J.; Schieren, Ira; Maniatis, Tom; Rabadan, Raul

2017-01-01

Transcriptional programs control cellular lineage commitment and differentiation during development. Understanding cell fate has been advanced by studying single-cell RNA-seq, but is limited by the assumptions of current analytic methods regarding the structure of data. We present single-cell topological data analysis (scTDA), an algorithm for topology-based computational analyses to study temporal, unbiased transcriptional regulation. Compared to other methods, scTDA is a non-linear, model-independent, unsupervised statistical framework that can characterize transient cellular states. We applied scTDA to the analysis of murine embryonic stem cell (mESC) differentiation in vitro in response to inducers of motor neuron differentiation. scTDA resolved asynchrony and continuity in cellular identity over time, and identified four transient states (pluripotent, precursor, progenitor, and fully differentiated cells) based on changes in stage-dependent combinations of transcription factors, RNA-binding proteins and long non-coding RNAs. scTDA can be applied to study asynchronous cellular responses to either developmental cues or environmental perturbations. PMID:28459448

Combining a leadership course and multi-source feedback has no effect on leadership skills of leaders in postgraduate medical education. An intervention study with a control group

PubMed Central

2009-01-01

Background Leadership courses and multi-source feedback are widely used developmental tools for leaders in health care. On this background we aimed to study the additional effect of a leadership course following a multi-source feedback procedure compared to multi-source feedback alone especially regarding development of leadership skills over time. Methods Study participants were consultants responsible for postgraduate medical education at clinical departments. Study design: pre-post measures with an intervention and control group. The intervention was participation in a seven-day leadership course. Scores of multi-source feedback from the consultants responsible for education and respondents (heads of department, consultants and doctors in specialist training) were collected before and one year after the intervention and analysed using Mann-Whitney's U-test and Multivariate analysis of variances. Results There were no differences in multi-source feedback scores at one year follow up compared to baseline measurements, either in the intervention or in the control group (p = 0.149). Conclusion The study indicates that a leadership course following a MSF procedure compared to MSF alone does not improve leadership skills of consultants responsible for education in clinical departments. Developing leadership skills takes time and the time frame of one year might have been too short to show improvement in leadership skills of consultants responsible for education. Further studies are needed to investigate if other combination of initiatives to develop leadership might have more impact in the clinical setting. PMID:20003311

Developmental Specificity in Targeting and Teaching Play Activities to Children with Pervasive Developmental Disorders

ERIC Educational Resources Information Center

Lifter, Karin; Ellis, James; Cannon, Barbara; Anderson, Stephen R.

2005-01-01

Developmentally specific play programs were designed for three children with pervasive developmental disorders being served in a home-based program. Using the Developmental Play Assessment, six activities for each of three adjacent developmentally sequenced play categories were targeted for direct instruction using different toy sets. A modified…

Multi -omics and metabolic modelling pipelines: challenges and tools for systems microbiology.

PubMed

Fondi, Marco; Liò, Pietro

2015-02-01

Integrated -omics approaches are quickly spreading across microbiology research labs, leading to (i) the possibility of detecting previously hidden features of microbial cells like multi-scale spatial organization and (ii) tracing molecular components across multiple cellular functional states. This promises to reduce the knowledge gap between genotype and phenotype and poses new challenges for computational microbiologists. We underline how the capability to unravel the complexity of microbial life will strongly depend on the integration of the huge and diverse amount of information that can be derived today from -omics experiments. In this work, we present opportunities and challenges of multi -omics data integration in current systems biology pipelines. We here discuss which layers of biological information are important for biotechnological and clinical purposes, with a special focus on bacterial metabolism and modelling procedures. A general review of the most recent computational tools for performing large-scale datasets integration is also presented, together with a possible framework to guide the design of systems biology experiments by microbiologists. Copyright © 2015. Published by Elsevier GmbH.

Quantitative analysis of tissue deformation dynamics reveals three characteristic growth modes and globally aligned anisotropic tissue deformation during chick limb development.

PubMed

Morishita, Yoshihiro; Kuroiwa, Atsushi; Suzuki, Takayuki

2015-05-01

Tissue-level characterization of deformation dynamics is crucial for understanding organ morphogenetic mechanisms, especially the interhierarchical links among molecular activities, cellular behaviors and tissue/organ morphogenetic processes. Limb development is a well-studied topic in vertebrate organogenesis. Nevertheless, there is still little understanding of tissue-level deformation relative to molecular and cellular dynamics. This is mainly because live recording of detailed cell behaviors in whole tissues is technically difficult. To overcome this limitation, by applying a recently developed Bayesian approach, we here constructed tissue deformation maps for chick limb development with high precision, based on snapshot lineage tracing using dye injection. The precision of the constructed maps was validated with a clear statistical criterion. From the geometrical analysis of the map, we identified three characteristic tissue growth modes in the limb and showed that they are consistent with local growth factor activity and cell cycle length. In particular, we report that SHH signaling activity changes dynamically with developmental stage and strongly correlates with the dynamic shift in the tissue growth mode. We also found anisotropic tissue deformation along the proximal-distal axis. Morphogenetic simulation and experimental studies suggested that this directional tissue elongation, and not local growth, has the greatest impact on limb shaping. This result was supported by the novel finding that anisotropic tissue elongation along the proximal-distal axis occurs independently of cell proliferation. Our study marks a pivotal point for multi-scale system understanding in vertebrate development. © 2015. Published by The Company of Biologists Ltd.

Space Propulsion Research Facility (B-2): An Innovative, Multi-Purpose Test Facility

NASA Technical Reports Server (NTRS)

Hill, Gerald M.; Weaver, Harold F.; Kudlac, Maureen T.; Maloney, Christian T.; Evans, Richard K.

2011-01-01

The Space Propulsion Research Facility, commonly referred to as B-2, is designed to hot fire rocket engines or upper stage launch vehicles with up to 890,000 N force (200,000 lb force), after environmental conditioning of the test article in simulated thermal vacuum space environment. As NASA s third largest thermal vacuum facility, and the largest designed to store and transfer large quantities of propellant, it is uniquely suited to support developmental testing associated with large lightweight structures and Cryogenic Fluid Management (CFM) systems, as well as non-traditional propulsion test programs such as Electric and In-Space propulsion. B-2 has undergone refurbishment of key subsystems to support the NASA s future test needs, including data acquisition and controls, vacuum, and propellant systems. This paper details the modernization efforts at B-2 to support the Nation s thermal vacuum/propellant test capabilities, the unique design considerations implemented for efficient operations and maintenance, and ultimately to reduce test costs.

Nicotine-induced plasticity during development: modulation of the cholinergic system and long-term consequences for circuits involved in attention and sensory processing.

PubMed

Heath, Christopher J; Picciotto, Marina R

2009-01-01

Despite a great deal of progress, more than 10% of pregnant women in the USA smoke. Epidemiological studies have demonstrated correlations between developmental tobacco smoke exposure and sensory processing deficits, as well as a number of neuropsychiatric conditions, including attention deficit hyperactivity disorder. Significantly, data from animal models of developmental nicotine exposure have suggested that the nicotine in tobacco contributes significantly to the effects of developmental smoke exposure. Consequently, we hypothesize that nicotinic acetylcholine receptors (nAChRs) are important for setting and refining the strength of corticothalamic-thalamocortical loops during critical periods of development and that disruption of this process by developmental nicotine exposure can result in long-lasting dysregulation of sensory processing. The ability of nAChR activation to modulate synaptic plasticity is likely to underlie the effects of both endogenous cholinergic signaling and pharmacologically administered nicotine to alter cellular, physiological and behavioral processes during critical periods of development.

The significance and scope of evolutionary developmental biology: a vision for the 21st century.

PubMed

Moczek, Armin P; Sears, Karen E; Stollewerk, Angelika; Wittkopp, Patricia J; Diggle, Pamela; Dworkin, Ian; Ledon-Rettig, Cristina; Matus, David Q; Roth, Siegfried; Abouheif, Ehab; Brown, Federico D; Chiu, Chi-Hua; Cohen, C Sarah; Tomaso, Anthony W De; Gilbert, Scott F; Hall, Brian; Love, Alan C; Lyons, Deirdre C; Sanger, Thomas J; Smith, Joel; Specht, Chelsea; Vallejo-Marin, Mario; Extavour, Cassandra G

2015-01-01

Evolutionary developmental biology (evo-devo) has undergone dramatic transformations since its emergence as a distinct discipline. This paper aims to highlight the scope, power, and future promise of evo-devo to transform and unify diverse aspects of biology. We articulate key questions at the core of eleven biological disciplines-from Evolution, Development, Paleontology, and Neurobiology to Cellular and Molecular Biology, Quantitative Genetics, Human Diseases, Ecology, Agriculture and Science Education, and lastly, Evolutionary Developmental Biology itself-and discuss why evo-devo is uniquely situated to substantially improve our ability to find meaningful answers to these fundamental questions. We posit that the tools, concepts, and ways of thinking developed by evo-devo have profound potential to advance, integrate, and unify biological sciences as well as inform policy decisions and illuminate science education. We look to the next generation of evolutionary developmental biologists to help shape this process as we confront the scientific challenges of the 21st century. © 2015 Wiley Periodicals, Inc.

Genome-Wide Reprogramming of Transcript Architecture by Temperature Specifies the Developmental States of the Human Pathogen Histoplasma

PubMed Central

Gilmore, Sarah A.; Voorhies, Mark; Gebhart, Dana; Sil, Anita

2015-01-01

Eukaryotic cells integrate layers of gene regulation to coordinate complex cellular processes; however, mechanisms of post-transcriptional gene regulation remain poorly studied. The human fungal pathogen Histoplasma capsulatum (Hc) responds to environmental or host temperature by initiating unique transcriptional programs to specify multicellular (hyphae) or unicellular (yeast) developmental states that function in infectivity or pathogenesis, respectively. Here we used recent advances in next-generation sequencing to uncover a novel re-programming of transcript length between Hc developmental cell types. We found that ~2% percent of Hc transcripts exhibit 5’ leader sequences that differ markedly in length between morphogenetic states. Ribosome density and mRNA abundance measurements of differential leader transcripts revealed nuanced transcriptional and translational regulation. One such class of regulated longer leader transcripts exhibited tight transcriptional and translational repression. Further examination of these dually repressed genes revealed that some control Hc morphology and that their strict regulation is necessary for the pathogen to make appropriate developmental decisions in response to temperature. PMID:26177267

Genome-Wide Reprogramming of Transcript Architecture by Temperature Specifies the Developmental States of the Human Pathogen Histoplasma.

PubMed

Gilmore, Sarah A; Voorhies, Mark; Gebhart, Dana; Sil, Anita

2015-07-01

Eukaryotic cells integrate layers of gene regulation to coordinate complex cellular processes; however, mechanisms of post-transcriptional gene regulation remain poorly studied. The human fungal pathogen Histoplasma capsulatum (Hc) responds to environmental or host temperature by initiating unique transcriptional programs to specify multicellular (hyphae) or unicellular (yeast) developmental states that function in infectivity or pathogenesis, respectively. Here we used recent advances in next-generation sequencing to uncover a novel re-programming of transcript length between Hc developmental cell types. We found that ~2% percent of Hc transcripts exhibit 5' leader sequences that differ markedly in length between morphogenetic states. Ribosome density and mRNA abundance measurements of differential leader transcripts revealed nuanced transcriptional and translational regulation. One such class of regulated longer leader transcripts exhibited tight transcriptional and translational repression. Further examination of these dually repressed genes revealed that some control Hc morphology and that their strict regulation is necessary for the pathogen to make appropriate developmental decisions in response to temperature.

Toxcast Profiling in a Human Stem Cell Assay for Developmental Toxicity (SOT)

EPA Science Inventory

We correlated the ToxCast library in a metabolic biomarker-based in vitro assay (Stemina devTOXqP) utilizing human embryonic stem (hES) cells (H9 line). This assay identifies the concentration of a chemical that disrupts cellular metabolism in a manner indicative of teratogenic...

Epigenetics and the Biological Definition of Gene X Environment Interactions

ERIC Educational Resources Information Center

Meaney, Michael J.

2010-01-01

Variations in phenotype reflect the influence of environmental conditions during development on cellular functions, including that of the genome. The recent integration of epigenetics into developmental psychobiology illustrates the processes by which environmental conditions in early life structurally alter DNA, providing a physical basis for the…

Developmental Patterning: Putting the Squeeze on Mis-specified Cells.

PubMed

Nakajima, Yu-Ichiro; Gibson, Matthew C

2016-03-07

Widely implicated in human disease, abnormal cellular cysts reflect dramatic defects in the maintenance of epithelial integrity. A new study reports that epithelial cysts may arise as a surprisingly general consequence of clonal defects in the specification of cell identity. Copyright © 2016 Elsevier Ltd. All rights reserved.

78 FR 59040 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-25

..., [email protected] . Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated... Scientific Review Special Emphasis Panel, RFA Panel: Molecular Probes. Date: October 18, 2013. Time: 8:00 a.m... Assistance Program Nos. 93.306, Comparative Medicine; 93.333, Clinical Research, 93.306, 93.333, 93.337, 93...

77 FR 1704 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-11

... Medicine. Date: February 1-2, 2012. Time: 11:30 a.m. to 5 p.m. Agenda: To review and evaluate grant...-7314, [email protected] . Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review Group; Molecular Neuropharmacology and Signaling Study Section. Date: February 6-7, 2012...

78 FR 53463 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-29

...: Molecular, Cellular and Developmental Neuroscience Integrated Review Group; Neurotransporters, Receptors... Discovery and Molecular Pharmacology Study Section. Date: September 30, 2013. Time: 8:00 a.m. to 6:00 p.m....nih.gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.306, Comparative Medicine; 93.333...

76 FR 31619 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-01

... personal privacy. Name of Committee: Center for Scientific Review Special Emphasis Panel, Molecular Genetics Applications. Date: June 20, 2011. Time: 12:30 p.m. to 3 p.m. Agenda: To review and evaluate grant... Emphasis Panel, Small Business: Molecular, Cellular and Developmental Neurobiology. Date: June 30, 2011...

The SIX1 Oncoprotein Mediates Aberrant Endometrial Basal Cell Development Following Neonatal Exposure to Diethylstilbestrol

EPA Science Inventory

Early-life exposures can disrupt cellular differentiation and contribute to increased cancer risk later in life. In a model of developmental estrogen exposure, female mice exposed on postnatal day (PND) 1-5 to diethylstilbestrol (DES) develop a high incidence of endometrial adeno...

Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

EPA Science Inventory

There is a need for rapid, efficient and cost effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be...

Genome-Wide Immune Modulation of TLR3-Mediated Inflammation in Intestinal Epithelial Cells Differs between Single and Multi-Strain Probiotic Combination.

PubMed

MacPherson, Chad W; Shastri, Padmaja; Mathieu, Olivier; Tompkins, Thomas A; Burguière, Pierre

2017-01-01

Genome-wide transcriptional analysis in intestinal epithelial cells (IEC) can aid in elucidating the impact of single versus multi-strain probiotic combinations on immunological and cellular mechanisms of action. In this study we used human expression microarray chips in an in vitro intestinal epithelial cell model to investigate the impact of three probiotic bacteria, Lactobacillus helveticus R0052 (Lh-R0052), Bifidobacterium longum subsp. infantis R0033 (Bl-R0033) and Bifidobacterium bifidum R0071 (Bb-R0071) individually and in combination, and of a surface-layer protein (SLP) purified from Lh-R0052, on HT-29 cells' transcriptional profile to poly(I:C)-induced inflammation. Hierarchical heat map clustering, Set Distiller and String analyses revealed that the effects of Lh-R0052 and Bb-R0071 diverged from those of Bl-R0033 and Lh-R0052-SLP. It was evident from the global analyses with respect to the immune, cellular and homeostasis related pathways that the co-challenge with probiotic combination (PC) vastly differed in its effect from the single strains and Lh-R0052-SLP treatments. The multi-strain PC resulted in a greater reduction of modulated genes, found through functional connections between immune and cellular pathways. Cytokine and chemokine analyses based on specific outcomes from the TNF-α and NF-κB signaling pathways revealed single, multi-strain and Lh-R0052-SLP specific attenuation of the majority of proteins measured (TNF-α, IL-8, CXCL1, CXCL2 and CXCL10), indicating potentially different mechanisms. These findings indicate a synergistic effect of the bacterial combinations relative to the single strain and Lh-R0052-SLP treatments in resolving toll-like receptor 3 (TLR3)-induced inflammation in IEC and maintaining cellular homeostasis, reinforcing the rationale for using multi-strain formulations as a probiotic.

Genome-Wide Immune Modulation of TLR3-Mediated Inflammation in Intestinal Epithelial Cells Differs between Single and Multi-Strain Probiotic Combination

PubMed Central

MacPherson, Chad W.; Shastri, Padmaja; Mathieu, Olivier; Tompkins, Thomas A.; Burguière, Pierre

2017-01-01

Genome-wide transcriptional analysis in intestinal epithelial cells (IEC) can aid in elucidating the impact of single versus multi-strain probiotic combinations on immunological and cellular mechanisms of action. In this study we used human expression microarray chips in an in vitro intestinal epithelial cell model to investigate the impact of three probiotic bacteria, Lactobacillus helveticus R0052 (Lh-R0052), Bifidobacterium longum subsp. infantis R0033 (Bl-R0033) and Bifidobacterium bifidum R0071 (Bb-R0071) individually and in combination, and of a surface-layer protein (SLP) purified from Lh-R0052, on HT-29 cells’ transcriptional profile to poly(I:C)-induced inflammation. Hierarchical heat map clustering, Set Distiller and String analyses revealed that the effects of Lh-R0052 and Bb-R0071 diverged from those of Bl-R0033 and Lh-R0052-SLP. It was evident from the global analyses with respect to the immune, cellular and homeostasis related pathways that the co-challenge with probiotic combination (PC) vastly differed in its effect from the single strains and Lh-R0052-SLP treatments. The multi-strain PC resulted in a greater reduction of modulated genes, found through functional connections between immune and cellular pathways. Cytokine and chemokine analyses based on specific outcomes from the TNF-α and NF-κB signaling pathways revealed single, multi-strain and Lh-R0052-SLP specific attenuation of the majority of proteins measured (TNF-α, IL-8, CXCL1, CXCL2 and CXCL10), indicating potentially different mechanisms. These findings indicate a synergistic effect of the bacterial combinations relative to the single strain and Lh-R0052-SLP treatments in resolving toll-like receptor 3 (TLR3)-induced inflammation in IEC and maintaining cellular homeostasis, reinforcing the rationale for using multi-strain formulations as a probiotic. PMID:28099447

Cellular computational generalized neuron network for frequency situational intelligence in a multi-machine power system.

PubMed

Wei, Yawei; Venayagamoorthy, Ganesh Kumar

2017-09-01

To prevent large interconnected power system from a cascading failure, brownout or even blackout, grid operators require access to faster than real-time information to make appropriate just-in-time control decisions. However, the communication and computational system limitations of currently used supervisory control and data acquisition (SCADA) system can only deliver delayed information. However, the deployment of synchrophasor measurement devices makes it possible to capture and visualize, in near-real-time, grid operational data with extra granularity. In this paper, a cellular computational network (CCN) approach for frequency situational intelligence (FSI) in a power system is presented. The distributed and scalable computing unit of the CCN framework makes it particularly flexible for customization for a particular set of prediction requirements. Two soft-computing algorithms have been implemented in the CCN framework: a cellular generalized neuron network (CCGNN) and a cellular multi-layer perceptron network (CCMLPN), for purposes of providing multi-timescale frequency predictions, ranging from 16.67 ms to 2 s. These two developed CCGNN and CCMLPN systems were then implemented on two different scales of power systems, one of which installed a large photovoltaic plant. A real-time power system simulator at weather station within the Real-Time Power and Intelligent Systems (RTPIS) laboratory at Clemson, SC, was then used to derive typical FSI results. Copyright © 2017 Elsevier Ltd. All rights reserved.

Discrepancy between mRNA and protein abundance: Insight from information retrieval process in computers

PubMed Central

Wang, Degeng

2008-01-01

Discrepancy between the abundance of cognate protein and RNA molecules is frequently observed. A theoretical understanding of this discrepancy remains elusive, and it is frequently described as surprises and/or technical difficulties in the literature. Protein and RNA represent different steps of the multi-stepped cellular genetic information flow process, in which they are dynamically produced and degraded. This paper explores a comparison with a similar process in computers - multi-step information flow from storage level to the execution level. Functional similarities can be found in almost every facet of the retrieval process. Firstly, common architecture is shared, as the ribonome (RNA space) and the proteome (protein space) are functionally similar to the computer primary memory and the computer cache memory respectively. Secondly, the retrieval process functions, in both systems, to support the operation of dynamic networks – biochemical regulatory networks in cells and, in computers, the virtual networks (of CPU instructions) that the CPU travels through while executing computer programs. Moreover, many regulatory techniques are implemented in computers at each step of the information retrieval process, with a goal of optimizing system performance. Cellular counterparts can be easily identified for these regulatory techniques. In other words, this comparative study attempted to utilize theoretical insight from computer system design principles as catalysis to sketch an integrative view of the gene expression process, that is, how it functions to ensure efficient operation of the overall cellular regulatory network. In context of this bird’s-eye view, discrepancy between protein and RNA abundance became a logical observation one would expect. It was suggested that this discrepancy, when interpreted in the context of system operation, serves as a potential source of information to decipher regulatory logics underneath biochemical network operation. PMID:18757239

Discrepancy between mRNA and protein abundance: insight from information retrieval process in computers.

PubMed

Wang, Degeng

2008-12-01

Discrepancy between the abundance of cognate protein and RNA molecules is frequently observed. A theoretical understanding of this discrepancy remains elusive, and it is frequently described as surprises and/or technical difficulties in the literature. Protein and RNA represent different steps of the multi-stepped cellular genetic information flow process, in which they are dynamically produced and degraded. This paper explores a comparison with a similar process in computers-multi-step information flow from storage level to the execution level. Functional similarities can be found in almost every facet of the retrieval process. Firstly, common architecture is shared, as the ribonome (RNA space) and the proteome (protein space) are functionally similar to the computer primary memory and the computer cache memory, respectively. Secondly, the retrieval process functions, in both systems, to support the operation of dynamic networks-biochemical regulatory networks in cells and, in computers, the virtual networks (of CPU instructions) that the CPU travels through while executing computer programs. Moreover, many regulatory techniques are implemented in computers at each step of the information retrieval process, with a goal of optimizing system performance. Cellular counterparts can be easily identified for these regulatory techniques. In other words, this comparative study attempted to utilize theoretical insight from computer system design principles as catalysis to sketch an integrative view of the gene expression process, that is, how it functions to ensure efficient operation of the overall cellular regulatory network. In context of this bird's-eye view, discrepancy between protein and RNA abundance became a logical observation one would expect. It was suggested that this discrepancy, when interpreted in the context of system operation, serves as a potential source of information to decipher regulatory logics underneath biochemical network operation.

The neurite growth inhibitory effects of soluble TNFα on developing sympathetic neurons are dependent on developmental age.

PubMed

Nolan, Aoife M; Collins, Louise M; Wyatt, Sean L; Gutierrez, Humberto; O'Keeffe, Gerard W

2014-01-01

During development, the growth of neural processes is regulated by an array of cellular and molecular mechanisms which influence growth rate, direction and branching. Recently, many members of the TNF superfamily have been shown to be key regulators of neurite growth during development. The founder member of this family, TNFα can both promote and inhibit neurite growth depending on the cellular context. Specifically, transmembrane TNFα promotes neurite growth, while soluble TNFα inhibits it. While the growth promoting effects of TNFα are restricted to a defined developmental window of early postnatal development, whether the growth inhibitory effects of soluble TNFα occur throughout development is unknown. In this study we used the extensively studied, well characterised neurons of the superior cervical ganglion to show that the growth inhibitory effects of soluble TNFα are restricted to a specific period of late embryonic and early postnatal development. Furthermore, we show that this growth inhibitory effect of soluble TNFα requires NF-κB signalling at all developmental stages at which soluble TNFα inhibits neurite growth. These findings raise the possibility that increases in the amount of soluble TNFα in vivo, for example as a result of maternal inflammation, could negatively affect neurite growth in developing neurons at specific stages of development. Copyright © 2015 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Cellular and Molecular Dynamics of Th17 Differentiation and its Developmental Plasticity in the Intestinal Immune Response

PubMed Central

Bhaumik, Suniti; Basu, Rajatava

2017-01-01

After emerging from the thymus, naive CD4 T cells circulate through secondary lymphoid tissues, including gut-associated lymphoid tissue of the intestine. The activation of naïve CD4 T cells by antigen-presenting cells offering cognate antigen initiate differentiation programs that lead to the development of highly specialized T helper (Th) cell lineages. Although initially believed that developmental programing of effector T cells such as T helper 1 (Th1) or T helper 2 (Th2) resulted in irreversible commitment to a fixed fate, subsequent studies have demonstrated greater flexibility, or plasticity, in effector T cell stability than originally conceived. This is particularly so for the Th17 subset, differentiation of which is a highly dynamic process with overlapping developmental axes with inducible regulatory T (iTreg), T helper 22 (Th22), and Th1 cells. Accordingly, intermediary stages of Th17 cells are found in various tissues, which co-express lineage-specific transcription factor(s) or cytokine(s) of developmentally related CD4 T cell subsets. A highly specialized tissue like that of the intestine, which harbors the largest immune compartment of the body, adds several layers of complexity to the intricate process of Th differentiation. Due to constant exposure to millions of commensal microbes and periodic exposure to pathogens, the intestinal mucosa maintains a delicate balance between regulatory and effector T cells. It is becoming increasingly clear that equilibrium between tolerogenic and inflammatory axes is maintained in the intestine by shuttling the flexible genetic programming of a developing CD4 T cell along the developmental axis of iTreg, Th17, Th22, and Th1 subsets. Currently, Th17 plasticity remains an unresolved concern in the field of clinical research as targeting Th17 cells to cure immune-mediated disease might also target its related subsets. In this review, we discuss the expanding sphere of Th17 plasticity through its shared developmental axes with related cellular subsets such as Th22, Th1, and iTreg in the context of intestinal inflammation and also examine the molecular and epigenetic features of Th17 cells that mediate these overlapping developmental programs. PMID:28408906

Multi-casting approach for vascular networks in cellularized hydrogels.

PubMed

Justin, Alexander W; Brooks, Roger A; Markaki, Athina E

2016-12-01

Vascularization is essential for living tissue and remains a major challenge in the field of tissue engineering. A lack of a perfusable channel network within a large and densely populated tissue engineered construct leads to necrotic core formation, preventing fabrication of functional tissues and organs. We report a new method for producing a hierarchical, three-dimensional (3D) and perfusable vasculature in a large, cellularized fibrin hydrogel. Bifurcating channels, varying in size from 1 mm to 200-250 µm, are formed using a novel process in which we convert a 3D printed thermoplastic material into a gelatin network template, by way of an intermediate alginate hydrogel. This enables a CAD-based model design, which is highly customizable, reproducible, and which can yield highly complex architectures, to be made into a removable material, which can be used in cellular environments. Our approach yields constructs with a uniform and high density of cells in the bulk, made from bioactive collagen and fibrin hydrogels. Using standard cell staining and immuno-histochemistry techniques, we showed good cell seeding and the presence of tight junctions between channel endothelial cells, and high cell viability and cell spreading in the bulk hydrogel. © 2016 The Authors.

Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway

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

Wang, Yi; Wei, Wei; Wang, Yuan

Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism onmore » long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and hypothyroidism. - Highlights: • Neurotoxicity of developmental hypothyroxinemia impaired LTP. • Decreased activation of PI3K signaling contributed to LTP impairments. • The recovery of TH after the developmental period did not prevent LTP impairments. • ID diet successfully induced neurotoxicity of developmental hypothyroxinemia.« less

Examining the Criterion-Related Validity of the Pervasive Developmental Disorder Behavior Inventory

ERIC Educational Resources Information Center

McMorris, Carly A.; Perry, Adrienne

2015-01-01

The Pervasive Developmental Disorder Behavior Inventory is a questionnaire designed to aid in the diagnosis of pervasive developmental disorders or autism spectrum disorders. The Pervasive Developmental Disorder Behavior Inventory assesses adaptive and maladaptive behaviors associated with pervasive developmental disorders and provides an…

A Model of Evolution of Development Based on Germline Penetration of New “No-Junk” DNA

PubMed Central

Fontana, Alessandro; Wróbel, Borys

2012-01-01

There is a mounting body of evidence that somatic transposition may be involved in normal development of multicellular organisms and in pathology, especially cancer. Epigenetic Tracking (ET) is an abstract model of multicellular development, able to generate complex 3-dimensional structures. Its aim is not to model the development of a particular organism nor to merely summarise mainstream knowledge on genetic regulation of development. Rather, the goal of ET is to provide a theoretical framework to test new postulated genetic mechanisms, not fully established yet in mainstream biology. The first proposal is that development is orchestrated through a subset of cells which we call driver cells. In these cells, the cellular state determines a specific pattern of gene activation which leads to the occurrence of developmental events. The second proposal is that evolution of development is affected by somatic transposition events. We postulate that when the genome of a driver cell does not specify what developmental event should be undertaken when the cell is in a particular cellular state, somatic transposition events can reshape the genome, build new regulatory regions, and lead to a new pattern of gene activation in the cell. Our third hypothesis, not supported yet by direct evidence, but consistent with some experimental observations, is that these new “no-junk” sequences—regulatory regions created by transposable elements at new positions in the genome—can exit the cell and enter the germline, to be incorporated in the genome of the progeny. We call this mechanism germline penetration. This process allows heritable incorporation of novel developmental events in the developmental trajectory. In this paper we will present the model and link these three postulated mechanisms to biological observations. PMID:24704981

The telomeric protein SNM1B/Apollo is required for normal cell proliferation and embryonic development.

PubMed

Akhter, Shamima; Lam, Yung C; Chang, Sandy; Legerski, Randy J

2010-12-01

Conserved metallo β-Lactamase and β-CASP (CPSF-Artemis-Snm1-Pso2) domain nuclease family member SNM1B/Apollo is a shelterin-associated protein that localizes to telomeres through its interaction with TRF2. To study its in vivo role, we generated a knockout of SNM1B/Apollo in a mouse model. Snm1B/Apollo homozygous null mice die at birth with developmental delay and defects in multiple organ systems. Cell proliferation defects were observed in Snm1B/Apollo mutant mouse embryonic fibroblasts (MEFs) owing to high levels of telomeric end-to-end fusions. Deficiency of the nonhomologous end-joining (NHEJ) factor Ku70, but not p53, rescued the developmental defects and lethality observed in Snm1B/Apollo mutant mice as well as the impaired proliferation of Snm1B/Apollo-deficient MEFs. These findings demonstrate that SNM1B/Apollo is required to protect telomeres against NHEJ-mediated repair, which results in genomic instability and the consequent multi-organ developmental failure. Although Snm1B/Apollo-deficient MEFs exhibited high levels of apoptosis, abrogation of p53-dependent programmed cell death did not rescue the multi-organ developmental failure in the mice. © 2010 The Authors. Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

Developmental plasticity of mitochondrial function in American alligators, Alligator mississippiensis

PubMed Central

Crossley, Janna; Elsey, Ruth M.; Dzialowski, Edward M.; Shiels, Holly A.; Crossley, Dane A.

2016-01-01

The effect of hypoxia on cellular metabolism is well documented in adult vertebrates, but information is entirely lacking for embryonic organisms. The effect of hypoxia on embryonic physiology is particularly interesting, as metabolic responses during development may have life-long consequences, due to developmental plasticity. To this end, we investigated the effects of chronic developmental hypoxia on cardiac mitochondrial function in embryonic and juvenile American alligators (Alligator mississippiensis). Alligator eggs were incubated in 21% or 10% oxygen from 20 to 90% of embryonic development. Embryos were either harvested at 90% development or allowed to hatch and then reared in 21% oxygen for 3 yr. Ventricular mitochondria were isolated from embryonic/juvenile alligator hearts. Mitochondrial respiration and enzymatic activities of electron transport chain complexes were measured with a microrespirometer and spectrophotometer, respectively. Developmental hypoxia induced growth restriction and increased relative heart mass, and this phenotype persisted into juvenile life. Embryonic mitochondrial function was not affected by developmental hypoxia, but at the juvenile life stage, animals from hypoxic incubations had lower levels of Leak respiration and higher respiratory control ratios, which is indicative of enhanced mitochondrial efficiency. Our results suggest developmental hypoxia can have life-long consequences for alligator morphology and metabolic function. Further investigations are necessary to reveal the adaptive significance of the enhanced mitochondrial efficiency in the hypoxic phenotype. PMID:27707718

Differential Immunotoxicity Induced by Two Different Windows of Developmental Trichloroethylene Exposure

PubMed Central

Gilbert, Kathleen M.; Woodruff, William; Blossom, Sarah J.

2014-01-01

Developmental exposure to environmental toxicants may induce immune system alterations that contribute to adult stage autoimmune disease. We have shown that continuous exposure of MRL+/+ mice to trichloroethylene (TCE) from gestational day (GD) 0 to postnatal day (PND) 49 alters several aspects of CD4+ T cell function. This window of exposure corresponds to conception-adolescence/young adulthood in humans. More narrowly defining the window of TCE developmental exposure causes immunotoxicity that would establish the stage at which avoidance and/or intervention would be most effective. The current study divided continuous TCE exposure into two separate windows, namely, gestation only (GD0 to birth (PND0)) and early-life only (PND0-PND49). The mice were examined for specific alterations in CD4+ T cell function at PND49. One potentially long-lasting effect of developmental exposure, alterations in retrotransposon expression indicative of epigenetic alterations, was found in peripheral CD4+ T cells from both sets of developmentally exposed mice. Interestingly, certain other effects, such as alterations in thymus cellularity, were only found in mice exposed to TCE during gestation. In contrast, expansion of memory/activation cell subset of peripheral CD4+ T cells were only found in mice exposed to TCE during early life. Different windows of developmental TCE exposure can have different functional consequences. PMID:24696780

Non-contact multi-frequency magnetic induction spectroscopy system for industrial-scale bio-impedance measurement

NASA Astrophysics Data System (ADS)

O'Toole, M. D.; Marsh, L. A.; Davidson, J. L.; Tan, Y. M.; Armitage, D. W.; Peyton, A. J.

2015-03-01

Biological tissues have a complex impedance, or bio-impedance, profile which changes with respect to frequency. This is caused by dispersion mechanisms which govern how the electromagnetic field interacts with the tissue at the cellular and molecular level. Measuring the bio-impedance spectra of a biological sample can potentially provide insight into the sample’s properties and its cellular structure. This has obvious applications in the medical, pharmaceutical and food-based industrial domains. However, measuring the bio-impedance spectra non-destructively and in a way which is practical at an industrial scale presents substantial challenges. The low conductivity of the sample requires a highly sensitive instrument, while the demands of industrial-scale operation require a fast high-throughput sensor of rugged design. In this paper, we describe a multi-frequency magnetic induction spectroscopy (MIS) system suitable for industrial-scale, non-contact, spectroscopic bio-impedance measurement over a bandwidth of 156 kHz-2.5 MHz. The system sensitivity and performance are investigated using calibration and known reference samples. It is shown to yield rapid and consistently sensitive results with good long-term stability. The system is then used to obtain conductivity spectra of a number of biological test samples, including yeast suspensions of varying concentration and a range of agricultural produce, such as apples, pears, nectarines, kiwis, potatoes, oranges and tomatoes.

Culture on electrospun polyurethane scaffolds decreases atrial natriuretic peptide expression by cardiomyocytes in vitro.

PubMed

Rockwood, Danielle N; Akins, Robert E; Parrag, Ian C; Woodhouse, Kimberly A; Rabolt, John F

2008-12-01

The function of the mammalian heart depends on the functional alignment of cardiomyocytes, and controlling cell alignment is an important consideration in biomaterial design for cardiac tissue engineering and research. The physical cues that guide functional cell alignment in vitro and the impact of substrate-imposed alignment on cell phenotype, however, are only partially understood. In this report, primary cardiac ventricular cells were grown on electrospun, biodegradable polyurethane (ES-PU) with either aligned or unaligned microfibers. ES-PU scaffolds supported high-density cultures and cell subpopulations remained intact over two weeks in culture. ES-PU cultures contained electrically-coupled cardiomyocytes with connexin-43 localized to points of cell:cell contact. Multi-cellular organization correlated with microfiber orientation and aligned materials yielded highly oriented cardiomyocyte groupings. Atrial natriuretic peptide, a molecular marker that shows decreasing expression during ventricular cell maturation, was significantly lower in cultures grown on ES-PU scaffolds than in those grown on tissue culture polystyrene. Cells grown on aligned ES-PU had significantly lower steady state levels of ANP and constitutively released less ANP over time indicating that scaffold-imposed cell organization resulted in a shift in cell phenotype to a more mature state. We conclude that the physical organization of microfibers in ES-PU scaffolds impacts both multi-cellular architecture and cardiac cell phenotype in vitro.

Test Review: Siegel, B. (2004). "Pervasive Developmental Disorder Screening Test--II (PDDST-II)." San Antonio, TX: Harcourt

ERIC Educational Resources Information Center

Montgomery, Janine M.; Duncan, C. Randy; Francis, Garnett C.

2007-01-01

The "Pervasive Developmental Disorder Screening Test-II (PDDST-II)--Early Childhood Screener for Autistic Spectrum Disorders" is a clinical screening tool for pervasive developmental disorders (PDD) or autism spectrum disorders (ASD) designed for use by nonspecialist clinicians. It was designed to differentiate children as young as 18 months who…

Biomimetic stratified scaffold design for ligament-to-bone interface tissue engineering.

PubMed

Lu, Helen H; Spalazzi, Jeffrey P

2009-07-01

The emphasis in the field of orthopaedic tissue engineering is on imparting biomimetic functionality to tissue engineered bone or soft tissue grafts and enabling their translation to the clinic. A significant challenge in achieving extended graft functionality is engineering the biological fixation of these grafts with each other as well as with the host environment. Biological fixation will require re-establishment of the structure-function relationship inherent at the native soft tissue-to-bone interface on these tissue engineered grafts. To this end, strategic biomimicry must be incorporated into advanced scaffold design. To facilitate integration between distinct tissue types (e.g., bone with soft tissues such as cartilage, ligament, or tendon), a stratified or multi-phasic scaffold with distinct yet continuous tissue regions is required to pre-engineer the interface between bone and soft tissues. Using the ACL-to-bone interface as a model system, this review outlines the strategies for stratified scaffold design for interface tissue engineering, focusing on identifying the relevant design parameters derived from an understanding of the structure-function relationship inherent at the soft-to-hard tissue interface. The design approach centers on first addressing the challenge of soft tissue-to-bone integration ex vivo, and then subsequently focusing on the relatively less difficult task of bone-to-bone integration in vivo. In addition, we will review stratified scaffold design aimed at exercising spatial control over heterotypic cellular interactions, which are critical for facilitating the formation and maintenance of distinct yet continuous multi-tissue regions. Finally, potential challenges and future directions in this emerging area of advanced scaffold design will be discussed.

The Epidermis of Grhl3-Null Mice Displays Altered Lipid Processing and Cellular Hyperproliferation

PubMed Central

Ting, Stephen B; Caddy, Jacinta; Wilanowski, Tomasz; Auden, Alana; Cunningham, John M; Elias, Peter M; Holleran, Walter M

2005-01-01

The presence of an impermeable surface barrier is an essential homeostatic mechanism in almost all living organisms. We have recently described a novel gene that is critical for the developmental instruction and repair of the integument in mammals. This gene, Grainy head-like 3 (Grhl3) is a member of a large family of transcription factors that are homologs of the Drosophila developmental gene grainy head (grh). Mice lacking Grhl3 fail to form an adequate skin barrier, and die at birth due to dehydration. These animals are also unable to repair the epidermis, exhibiting failed wound healing in both fetal and adult stages of development. These defects are due, in part, to diminished expression of a Grhl3 target gene, Transglutaminase 1 (TGase 1), which encodes a key enzyme involved in cross-linking of epidermal structural proteins and lipids into the cornified envelope (CE). Remarkably, the Drosophila grh gene plays an analogous role, regulating enzymes involved in the generation of quinones, which are essential for cross-linking structural components of the fly epidermis. In an extension of our initial analyses, we focus this report on additional defects observed in the Grhl3-null epidermis, namely defective extra-cellular lipid processing, altered lamellar lipid architecture and cellular hyperproliferation. These abnormalities suggest that Grhl3 plays diverse mechanistic roles in maintaining homeostasis in the skin. PMID:19521564

The epidermis of grhl3-null mice displays altered lipid processing and cellular hyperproliferation.

PubMed

Ting, Stephen B; Caddy, Jacinta; Wilanowski, Tomasz; Auden, Alana; Cunningham, John M; Elias, Peter M; Holleran, Walter M; Jane, Stephen M

2005-04-01

The presence of an impermeable surface barrier is an essential homeostatic mechanism in almost all living organisms. We have recently described a novel gene that is critical for the developmental instruction and repair of the integument in mammals. This gene, Grainy head-like 3 (Grhl3) is a member of a large family of transcription factors that are homologs of the Drosophila developmental gene grainy head (grh). Mice lacking Grhl3 fail to form an adequate skin barrier, and die at birth due to dehydration. These animals are also unable to repair the epidermis, exhibiting failed wound healing in both fetal and adult stages of development. These defects are due, in part, to diminished expression of a Grhl3 target gene, Transglutaminase 1 (TGase 1), which encodes a key enzyme involved in cross-linking of epidermal structural proteins and lipids into the cornified envelope (CE). Remarkably, the Drosophila grh gene plays an analogous role, regulating enzymes involved in the generation of quinones, which are essential for cross-linking structural components of the fly epidermis. In an extension of our initial analyses, we focus this report on additional defects observed in the Grhl3-null epidermis, namely defective extra-cellular lipid processing, altered lamellar lipid architecture and cellular hyperproliferation. These abnormalities suggest that Grhl3 plays diverse mechanistic roles in maintaining homeostasis in the skin.

Deriving excitatory neurons of the neocortex from pluripotent stem cells

PubMed Central

Hansen, David V.; Rubenstein, John L.R.; Kriegstein, Arnold R.

2011-01-01

The human cerebral cortex is an immensely complex structure that subserves critical functions that can be disrupted in developmental and degenerative disorders. Recent innovations in cellular reprogramming and differentiation techniques have provided new ways to study the cellular components of the cerebral cortex. Here we discuss approaches to generate specific subtypes of excitatory cortical neurons from pluripotent stem cells. We review spatial and temporal aspects of cortical neuron specification that can guide efforts to produce excitatory neuron subtypes with increased resolution. Finally, we discuss distinguishing features of human cortical development and their translational ramifications for cortical stem cell technologies. PMID:21609822

Conduct disorder in adolescent females: current state of research and study design of the FemNAT-CD consortium.

PubMed

Freitag, Christine M; Konrad, Kerstin; Stadler, Christina; De Brito, Stephane A; Popma, Arne; Herpertz, Sabine C; Herpertz-Dahlmann, Beate; Neumann, Inga; Kieser, Meinhard; Chiocchetti, Andreas G; Schwenck, Christina; Fairchild, Graeme

2018-06-09

Conduct disorder (CD) is a common and highly impairing psychiatric disorder of childhood and adolescence that frequently leads to poor physical and mental health outcomes in adulthood. The prevalence of CD is substantially higher in males than females, and partly due to this, most research on this condition has used all-male or predominantly male samples. Although the number of females exhibiting CD has increased in recent decades, the majority of studies on neurobiological measures, neurocognitive phenotypes, and treatments for CD have focused on male subjects only, despite strong evidence for sex differences in the aetiology and neurobiology of CD. Here, we selectively review the existing literature on CD and related phenotypes in females, focusing in particular on sex differences in CD symptoms, patterns of psychiatric comorbidity, and callous-unemotional personality traits. We also consider studies investigating the neurobiology of CD in females, with a focus on studies using genetic, structural and functional neuroimaging, psychophysiological, and neuroendocrinological methods. We end the article by providing an overview of the study design of the FemNAT-CD consortium, an interdisciplinary, multi-level and multi-site study that explicitly focuses on CD in females, but which is also investigating sex differences in the causes, developmental course, and neurobiological correlates of CD.

Full-field dual-color 100-nm super-resolution imaging reveals organization and dynamics of mitochondrial and ER networks.

PubMed

Brunstein, Maia; Wicker, Kai; Hérault, Karine; Heintzmann, Rainer; Oheim, Martin

2013-11-04

Most structured illumination microscopes use a physical or synthetic grating that is projected into the sample plane to generate a periodic illumination pattern. Albeit simple and cost-effective, this arrangement hampers fast or multi-color acquisition, which is a critical requirement for time-lapse imaging of cellular and sub-cellular dynamics. In this study, we designed and implemented an interferometric approach allowing large-field, fast, dual-color imaging at an isotropic 100-nm resolution based on a sub-diffraction fringe pattern generated by the interference of two colliding evanescent waves. Our all-mirror-based system generates illumination pat-terns of arbitrary orientation and period, limited only by the illumination aperture (NA = 1.45), the response time of a fast, piezo-driven tip-tilt mirror (10 ms) and the available fluorescence signal. At low µW laser powers suitable for long-period observation of life cells and with a camera exposure time of 20 ms, our system permits the acquisition of super-resolved 50 µm by 50 µm images at 3.3 Hz. The possibility it offers for rapidly adjusting the pattern between images is particularly advantageous for experiments that require multi-scale and multi-color information. We demonstrate the performance of our instrument by imaging mitochondrial dynamics in cultured cortical astrocytes. As an illustration of dual-color excitation dual-color detection, we also resolve interaction sites between near-membrane mitochondria and the endoplasmic reticulum. Our TIRF-SIM microscope provides a versatile, compact and cost-effective arrangement for super-resolution imaging, allowing the investigation of co-localization and dynamic interactions between organelles--important questions in both cell biology and neurophysiology.

Identification of calcium-dependent protein kinase (CDPK): A multi-functional gene family in Rafflesia cantleyi

NASA Astrophysics Data System (ADS)

Amini, Safoora; Goh, Hoe-Han; Wan, Kiew-Lian

2016-11-01

Rafflesia, a parasitic plant that belongs to the Rafflesiaceae family, is notable for producing the largest flowers in the world. This study focused on identification of Calcium-dependent protein kinases (CDPKs) due to their vital roles in plant growth and development, biotic and abiotic stress responses, and hormone signaling. RNA-seq data generated from three bud stages of Rafflesia cantleyi ie BS1, BS2, and BS3 and were assembled. Based on the BLAST searches of Rafflesia unique transcripts (UTs) to Arabidopsis TAIR database, a total of 14 unique transcripts (UTs) were identified as CDPK1 to CDPK5, CDPK7 to CDPK11, CDPK16, CDPK18, CDPK19, and CDPK28. These genes are expressed at all three bud stages of R. cantleyi with up-regulation pattern at BS1 vs. BS2 and BS2 vs. BS3. This result shows that the expression of CDPK gene family increases by developmental progress in Rafflesia in order to regulate biochemical and molecular changes at the cellular level in response to exposure to environmental changes. However, CDPKs functions in plants growth and defense process still need more experimental evidence to deeply understand their biological roles in R. cantleyi.

Instabilities in rapid solidification of multi-component alloys

NASA Astrophysics Data System (ADS)

Altieri, Anthony L.; Davis, Stephen H.

2017-10-01

Rapid solidification of multi-component liquids occurs in many modern applications such as additive manufacturing. In the present work the interface departures from equilibrium consist of the segregation coefficient and liquidus slope depending on front speed, the one-sided, frozen-temperature approximation, and the alloy behaving as the superposition of individual components. Linear-stability theory is applied, showing that the cellular and oscillatory instabilities of the binary case are modified. The addition of components tends to destabilize the interface while the addition of a single large-diffusivity material can entirely suppress the oscillatory mode. Multiple minima in the neutral curve for the cellular mode occur.

ML-Space: Hybrid Spatial Gillespie and Particle Simulation of Multi-Level Rule-Based Models in Cell Biology.

PubMed

Bittig, Arne T; Uhrmacher, Adelinde M

2017-01-01

Spatio-temporal dynamics of cellular processes can be simulated at different levels of detail, from (deterministic) partial differential equations via the spatial Stochastic Simulation algorithm to tracking Brownian trajectories of individual particles. We present a spatial simulation approach for multi-level rule-based models, which includes dynamically hierarchically nested cellular compartments and entities. Our approach ML-Space combines discrete compartmental dynamics, stochastic spatial approaches in discrete space, and particles moving in continuous space. The rule-based specification language of ML-Space supports concise and compact descriptions of models and to adapt the spatial resolution of models easily.

Multicolor Super-Resolution Fluorescence Imaging via Multi-Parameter Fluorophore Detection

PubMed Central

Bates, Mark; Dempsey, Graham T; Chen, Kok Hao; Zhuang, Xiaowei

2012-01-01

Understanding the complexity of the cellular environment will benefit from the ability to unambiguously resolve multiple cellular components, simultaneously and with nanometer-scale spatial resolution. Multicolor super-resolution fluorescence microscopy techniques have been developed to achieve this goal, yet challenges remain in terms of the number of targets that can be simultaneously imaged and the crosstalk between color channels. Herein, we demonstrate multicolor stochastic optical reconstruction microscopy (STORM) based on a multi-parameter detection strategy, which uses both the fluorescence activation wavelength and the emission color to discriminate between photo-activatable fluorescent probes. First, we obtained two-color super-resolution images using the near-infrared cyanine dye Alexa 750 in conjunction with a red cyanine dye Alexa 647, and quantified color crosstalk levels and image registration accuracy. Combinatorial pairing of these two switchable dyes with fluorophores which enhance photo-activation enabled multi-parameter detection of six different probes. Using this approach, we obtained six-color super-resolution fluorescence images of a model sample. The combination of multiple fluorescence detection parameters for improved fluorophore discrimination promises to substantially enhance our ability to visualize multiple cellular targets with sub-diffraction-limit resolution. PMID:22213647

Shaping dendritic spines in autism spectrum disorder: mTORC1-dependent macroautophagy.

PubMed

Bowling, Heather; Klann, Eric

2014-09-03

In this issue of Neuron, Tang et al. (2014) explore the relationship between developmental dendritic pruning, elevated mTORC1 signaling, macroautophagy, and autism spectrum disorder. The study provides valuable new insight into mTORC1-dependent cellular dysfunction and neurodevelopmental disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Embryological Development: Evolutionary History, Genetic Bias, and Cellular Environment Control the Flow of Developmental Events, Part II.

ERIC Educational Resources Information Center

Caplan, Arnold I.

1981-01-01

Emphasizes ectodermal-mesodermal interaction but focuses on the genesis of specialized structures like feathers (ectodermal) and muscles, cartilage, and bone. The sum of these interactions and other factors which govern normal development may be important in regulating the regeneration of particular structures in postembryonic individuals.…

The ULT1 and ULT2 trxG genes play overlapping roles in Arabidopsis development and gene regulation

USDA-ARS?s Scientific Manuscript database

The epigenetic regulation of gene expression is critical for ensuring the proper deployment and stability of defined genome transcription programs at specific developmental stages. The cellular memory of stable gene expression states during animal and plant development is mediated by the opposing ac...

A Kinesthetic Model Demonstrating Molecular Interactions Involved in Anterior-Posterior Pattern Formation in "Drosophila"

ERIC Educational Resources Information Center

Douglas, Kristin R.

2008-01-01

Prerequisites for the Developmental Biology course at Augustana College are introductory courses in zoology and cell biology. After introductory courses students appreciate the fact that proteins have three-dimensional structures; however, they often fail to recognize how protein interactions with other cellular components can lead to specific…

Apoptosis: A Four-Week Laboratory Investigation for Advanced Molecular and Cellular Biology Students

ERIC Educational Resources Information Center

DiBartolomeis, Susan M.; Mone, James P.

2003-01-01

Over the past decade, apoptosis has emerged as an important field of study central to ongoing research in many diverse fields, from developmental biology to cancer research. Apoptosis proceeds by a highly coordinated series of events that includes enzyme activation, DNA fragmentation, and alterations in plasma membrane permeability. The detection…

Molecular aspects of eye evolution and development: from the origin of retinal cells to the future of regenerative medicine.

PubMed

Ohuchi, Hideyo

2013-01-01

A central issue of evolutionary developmental biology is how the eye is diverged morphologically and functionally. However, the unifying mechanisms or schemes that govern eye diversification remain unsolved. In this review, I first introduce the concept of evolutionary developmental biology of the eye with a focus on photoreception, the fundamental property of retinal cells. Second, I summarize the early development of vertebrate eyes and the role of a homeobox gene, Lhx1, in subdivision of the retina into 2 domains, the neural retina and retinal pigmented epithelium of the optic primordium. The 2 retinal domains are essential components of the eye as they are found in such prototypic eyes as the extant planarian eye. Finally, I propose the presence of novel retinal cell subtypes with photosensory functions based on our recent work on atypical photopigments (opsins) in vertebrates. Since human diseases are attributable to the aberration of various types of cells due to alterations in gene expression, understanding the precise mechanisms of cellular diversification and unraveling the molecular profiles of cellular subtypes are essential to future regenerative medicine.

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

Oscillatory Protein Expression Dynamics Endows Stem Cells with Robust Differentiation Potential

PubMed Central

Kaneko, Kunihiko

2011-01-01

The lack of understanding of stem cell differentiation and proliferation is a fundamental problem in developmental biology. Although gene regulatory networks (GRNs) for stem cell differentiation have been partially identified, the nature of differentiation dynamics and their regulation leading to robust development remain unclear. Herein, using a dynamical system modeling cell approach, we performed simulations of the developmental process using all possible GRNs with a few genes, and screened GRNs that could generate cell type diversity through cell-cell interactions. We found that model stem cells that both proliferated and differentiated always exhibited oscillatory expression dynamics, and the differentiation frequency of such stem cells was regulated, resulting in a robust number distribution. Moreover, we uncovered the common regulatory motifs for stem cell differentiation, in which a combination of regulatory motifs that generated oscillatory expression dynamics and stabilized distinct cellular states played an essential role. These findings may explain the recently observed heterogeneity and dynamic equilibrium in cellular states of stem cells, and can be used to predict regulatory networks responsible for differentiation in stem cell systems. PMID:22073296

Analysis of Sir2E in the cellular slime mold Dictyostelium discoideum: cellular localization, spatial expression and overexpression.

PubMed

Katayama, Takahiro; Yasukawa, Hiro

2008-10-01

It has been reported that Dictyostelium discoideum encodes four silent information regulator 2 (Sir2) proteins (Sir2A-D) showing sequence similarity to human homologues of Sir2 (SIRT1-3). Further screening in a database revealed that D. discoideum encodes an additional Sir2 homologue (Sir2E). The amino acid sequence of Sir2E is not similar to those of SIRTs but is similar to those of proteins encoded by Giardia lamblia, Cryptosporidium hominis and Cryptosporidium parvum. Fluorescence of Sir2E-green fluorescent protein fusion protein was detected in the D. discoideum nucleus, indicating that Sir2E is a nuclear localizing protein. Reverse transcription-polymerase chain reaction and whole-mount in situ hybridization analyses showed that D. discoideum expressed sir2E in amoebae in the growth phase and in prestalk cells in the developmental phase. D. discoideum overexpressing sir2E grew faster than the wild type. These results indicate that Sir2E plays important roles both in the growth phase and developmental phase of D. discoideum.

Polygenic risk accelerates the developmental progression to heavy, persistent smoking and nicotine dependence: Evidence from a 4-Decade Longitudinal Study

PubMed Central

Moffitt, Terrie E; Baker, Timothy B; Biddle, Andrea K; Evans, James P; Harrington, HonaLee; Houts, Renate; Meier, Madeline; Sugden, Karen; Williams, Benjamin; Poulton, Richie; Caspi, Avshalom

2013-01-01

OBJECTIVE To test how genomic loci identified in genome-wide association studies (GWAS) influence the developmental progression of smoking behavior. DESIGN A 38-year prospective longitudinal study of a representative birth-cohort. SETTING The Dunedin Multidisciplinary Health and Development Study, New Zealand. PARTICIPANTS N=1037 male and female study members. MAIN EXPOSURES We assessed genetic risk with a multi-locus genetic risk score (GRS). The GRS was composed of single-nucleotide polymorphisms identified in three meta-analyses of GWAS of smoking quantity phenotypes. OUTCOME MEASURES Smoking initiation, conversion to daily smoking, progression to heavy smoking, nicotine dependence (Fagerstrom Test of Nicotine Dependence), and cessation difficulties were evaluated at eight assessments spanning ages 11-38 years. RESULTS Genetic risk score was unrelated to smoking initiation. However, individuals at higher genetic risk were more likely to convert to daily smoking as teenagers, progressed more rapidly from smoking initiation to heavy smoking, persisted longer in smoking heavily, developed nicotine dependence more frequently, were more reliant on smoking to cope with stress, and were more likely to fail in their cessation attempts. Further analysis revealed that two adolescent developmental phenotypes—early conversion to daily smoking and rapid progression to heavy smoking--mediated associations between the genetic risk score and mature phenotypes of persistent heavy smoking, nicotine dependence, and cessation failure. The genetic risk score predicted smoking risk over and above family history. CONCLUSIONS Initiatives that disrupt the developmental progression of smoking behavior among adolescents may mitigate genetic risks for developing adult smoking problems. Future genetic research may maximize discovery potential by focusing on smoking behavior soon after smoking initiation and by studying young smokers. PMID:23536134

Bioinformatics approaches to single-cell analysis in developmental biology.

PubMed

Yalcin, Dicle; Hakguder, Zeynep M; Otu, Hasan H

2016-03-01

Individual cells within the same population show various degrees of heterogeneity, which may be better handled with single-cell analysis to address biological and clinical questions. Single-cell analysis is especially important in developmental biology as subtle spatial and temporal differences in cells have significant associations with cell fate decisions during differentiation and with the description of a particular state of a cell exhibiting an aberrant phenotype. Biotechnological advances, especially in the area of microfluidics, have led to a robust, massively parallel and multi-dimensional capturing, sorting, and lysis of single-cells and amplification of related macromolecules, which have enabled the use of imaging and omics techniques on single cells. There have been improvements in computational single-cell image analysis in developmental biology regarding feature extraction, segmentation, image enhancement and machine learning, handling limitations of optical resolution to gain new perspectives from the raw microscopy images. Omics approaches, such as transcriptomics, genomics and epigenomics, targeting gene and small RNA expression, single nucleotide and structural variations and methylation and histone modifications, rely heavily on high-throughput sequencing technologies. Although there are well-established bioinformatics methods for analysis of sequence data, there are limited bioinformatics approaches which address experimental design, sample size considerations, amplification bias, normalization, differential expression, coverage, clustering and classification issues, specifically applied at the single-cell level. In this review, we summarize biological and technological advancements, discuss challenges faced in the aforementioned data acquisition and analysis issues and present future prospects for application of single-cell analyses to developmental biology. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Vygotskian Approach to Heterogeneous Communication and Multi/Cultural Literacy: Commentary on David Kellogg's "Taking Uptaking up, or, a Deconstructionist "Ontology of Difference" and a Developmental One"

ERIC Educational Resources Information Center

Hwang, SungWon

2009-01-01

In this commentary, I review Kellogg's comments on a recent editorial in the journal "Mind, Culture, and Activity" (Roth, 2008). Concerning Kellogg's code-switching model for learning language, I present and exemplify a dialectic problem of multi/cultural literacy: the first articulation that crosses the boundaries of cultures and languages…

PDT-based combinations in overcoming chemoresistance from stromal and heterotypic cellular communication (Conference Presentation)

NASA Astrophysics Data System (ADS)

Rizvi, Imran; Bulin, Anne-Laure; Anbil, Sriram R.; Briars, Emma A.; Vecchio, Daniela; Celli, Jonathan P.; Broekgaarden, Mans; Hasan, Tayyaba

2017-02-01

Targeting the molecular and cellular cues that influence treatment resistance in tumors is critical to effectively treating unresponsive populations of stubborn disease. The informed design of mechanism-based combinations is emerging as increasingly important to targeting resistance and improving the efficacy of conventional treatments, while minimizing toxicity. Photodynamic therapy (PDT) has been shown to synergize with conventional agents and to overcome the evasion pathways that cause resistance. Increasing evidence shows that PDT-based combinations cooperate mechanistically with, and improve the therapeutic index of, traditional chemotherapies. These and other findings emphasize the importance of including PDT as part of comprehensive treatment plans for cancer, particularly in complex disease sites. Identifying effective combinations requires a multi-faceted approach that includes the development of bioengineered cancer models and corresponding image analysis tools. The molecular and phenotypic basis of verteporfin-mediated PDT-based enhancement of chemotherapeutic efficacy and predictability in complex 3D models for ovarian cancer will be presented.

A Review of Intervention Programs to Prevent and Treat Behavioral Problems in Young Children with Developmental Disabilities

PubMed Central

Petrenko, Christie L. M.

2013-01-01

Children with developmental disabilities are at higher risk for internalizing and externalizing behavioral problems than children in the general population. Effective prevention and treatment programs are necessary to reduce the burden of behavioral problems in this population. The current review identified 17 controlled trials of nine intervention programs for young children with developmental disabilities, with parent training the most common type of intervention in this population. Nearly all studies demonstrated medium to large intervention effects on child behavior post-intervention. Preliminary evidence suggests interventions developed for the general population can be effective for children with developmental disabilities and their families. A greater emphasis on the prevention of behavior problems in young children with developmental disabilities prior to the onset of significant symptoms or clinical disorders is needed. Multi-component interventions may be more efficacious for child behavior problems and yield greater benefits for parent and family adjustment. Recommendations for future research directions are provided. PMID:24222982

Systems metabolic engineering: the creation of microbial cell factories by rational metabolic design and evolution.

PubMed

Furusawa, Chikara; Horinouchi, Takaaki; Hirasawa, Takashi; Shimizu, Hiroshi

2013-01-01

It is widely acknowledged that in order to establish sustainable societies, production processes should shift from petrochemical-based processes to bioprocesses. Because bioconversion technologies, in which biomass resources are converted to valuable materials, are preferable to processes dependent on fossil resources, the former should be further developed. The following two approaches can be adopted to improve cellular properties and obtain high productivity and production yield of target products: (1) optimization of cellular metabolic pathways involved in various bioprocesses and (2) creation of stress-tolerant cells that can be active even under severe stress conditions in the bioprocesses. Recent progress in omics analyses has facilitated the analysis of microorganisms based on bioinformatics data for molecular breeding and bioprocess development. Systems metabolic engineering is a new area of study, and it has been defined as a methodology in which metabolic engineering and systems biology are integrated to upgrade the designability of industrially useful microorganisms. This chapter discusses multi-omics analyses and rational design methods for molecular breeding. The first is an example of the rational design of metabolic networks for target production by flux balance analysis using genome-scale metabolic models. Recent progress in the development of genome-scale metabolic models and the application of these models to the design of desirable metabolic networks is also described in this example. The second is an example of evolution engineering with omics analyses for the creation of stress-tolerant microorganisms. Long-term culture experiments to obtain the desired phenotypes and omics analyses to identify the phenotypic changes are described here.

Genetics of human hydrocephalus

PubMed Central

Williams, Michael A.; Rigamonti, Daniele

2006-01-01

Human hydrocephalus is a common medical condition that is characterized by abnormalities in the flow or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. Human hydrocephalus can be classified into two clinical forms, congenital and acquired. Hydrocephalus is one of the complex and multifactorial neurological disorders. A growing body of evidence indicates that genetic factors play a major role in the pathogenesis of hydrocephalus. An understanding of the genetic components and mechanism of this complex disorder may offer us significant insights into the molecular etiology of impaired brain development and an accumulation of the cerebrospinal fluid in cerebral compartments during the pathogenesis of hydrocephalus. Genetic studies in animal models have started to open the way for understanding the underlying pathology of hydrocephalus. At least 43 mutants/loci linked to hereditary hydrocephalus have been identified in animal models and humans. Up to date, 9 genes associated with hydrocephalus have been identified in animal models. In contrast, only one such gene has been identified in humans. Most of known hydrocephalus gene products are the important cytokines, growth factors or related molecules in the cellular signal pathways during early brain development. The current molecular genetic evidence from animal models indicate that in the early development stage, impaired and abnormal brain development caused by abnormal cellular signaling and functioning, all these cellular and developmental events would eventually lead to the congenital hydrocephalus. Owing to our very primitive knowledge of the genetics and molecular pathogenesis of human hydrocephalus, it is difficult to evaluate whether data gained from animal models can be extrapolated to humans. Initiation of a large population genetics study in humans will certainly provide invaluable information about the molecular and cellular etiology and the developmental mechanisms of human hydrocephalus. This review summarizes the recent findings on this issue among human and animal models, especially with reference to the molecular genetics, pathological, physiological and cellular studies, and identifies future research directions. PMID:16773266

Human Factors Design Guide For Acquisition of Commercial-Off-The-Shelf Subsystems, Non-Developmental Items, and Developmental Systems

DOT National Transportation Integrated Search

1996-01-15

The Human Factors Design Guide (HFDG) provides reference information to assist : in the selection, analysis, design, development, and evaluation of new and m : odified Federal Aviation Administration (FAA) systems and equipment. A : preliminary editi...

Multigenerational and transgenerational effects of endocrine disrupting chemicals: A role for altered epigenetic regulation?

PubMed Central

Xin, Frances; Susiarjo, Martha; Bartolomei, Marisa S.

2015-01-01

Increasing evidence has highlighted the critical role of early life environment in shaping the future health outcomes of an individual. Moreover, recent studies have revealed that early life perturbations can affect the health of subsequent generations. Hypothesized mechanisms of multi- and transgenerational inheritance of abnormal developmental phenotypes include epigenetic misregulation in germ cells. In this review, we will focus on the available data demonstrating the ability of endocrine disrupting chemicals (EDCs), including bisphenol A (BPA), phthalates, and parabens, to alter epigenetic marks in rodents and humans. These epigenetic marks include DNA methylation, histone post-translational modifications, and non-coding RNAs. We also review the current evidence for multi- and transgenerational inheritance of abnormal developmental changes in the offspring following EDC exposure. Based on published results, we conclude that EDC exposure can alter the mouse and human epigenome, with variable tissue susceptibilities. Although increasing data suggest that exposure to EDCs is linked to transgenerational inheritance of reproductive, metabolic, or neurological phenotypes, more studies are needed to validate these observations and to elucidate further whether these developmental changes are directly associated with the relevant epigenetic alterations. PMID:26026600

A triple-mode hexa-standard reconfigurable TI cross-coupled ΣΔ modulator

NASA Astrophysics Data System (ADS)

Prakash A. V, Jos; Jose, Babita R.; Mathew, Jimson; Jose, Bijoy A.

2017-07-01

Hardware reconfigurability is an attractive solution for modern multi-standard wireless systems. This paper analyses the performance and implementation of an efficient triple-mode hexa-standard reconfigurable sigma-delta (∑Δ) modulator designed for six different wireless communication standards. Enhanced noise-shaping characteristics and increased digitisation rate, obtained by time-interleaved cross-coupling of ∑Δ paths, have been utilised for the modulator design. Power/hardware efficiency and the capability to acclimate the requirements of wide hexa-standard specifications are achieved by introducing an advanced noise-shaping structure, the dual-extended architecture. Simulation results of the proposed architecture using Hspice shows that the proposed modulator obtains a peak signal-to-noise ratio of 83.4/80.2/67.8/61.5/60.8/51.03 dB for hexa-standards, i.e. GSM/Bluetooth/GPS/WCDMA/WLAN/WiMAX standards with significantly less hardware and low operating frequency. The proposed architecture is implemented in 45 nm CMOS process using a 1 V supply and 0.7 V input range with a power consumption of 1.93 mW. Both architectural- and transistor-level simulation results prove the effectiveness and feasibility of this architecture to accomplish multi-standard cellular communication characteristics.

Inner ear development: building a spiral ganglion and an organ of Corti out of unspecified ectoderm.

PubMed

Fritzsch, Bernd; Pan, Ning; Jahan, Israt; Elliott, Karen L

2015-07-01

The mammalian inner ear develops from a placodal thickening into a complex labyrinth of ducts with five sensory organs specialized to detect position and movement in space. The mammalian ear also develops a spiraled cochlear duct containing the auditory organ, the organ of Corti (OC), specialized to translate sound into hearing. Development of the OC from a uniform sheet of ectoderm requires unparalleled precision in the topological developmental engineering of four different general cell types, namely sensory neurons, hair cells, supporting cells, and general otic epithelium, into a mosaic of ten distinctly recognizable cell types in and around the OC, each with a unique distribution. Moreover, the OC receives unique innervation by ear-derived spiral ganglion afferents and brainstem-derived motor neurons as efferents and requires neural-crest-derived Schwann cells to form myelin and neural-crest-derived cells to induce the stria vascularis. This transformation of a sheet of cells into a complicated interdigitating set of cells necessitates the orchestrated expression of multiple transcription factors that enable the cellular transformation from ectoderm into neurosensory cells forming the spiral ganglion neurons (SGNs), while simultaneously transforming the flat epithelium into a tube, the cochlear duct, housing the OC. In addition to the cellular and conformational changes forming the cochlear duct with the OC, changes in the surrounding periotic mesenchyme form passageways for sound to stimulate the OC. We review molecular developmental data, generated predominantly in mice, in order to integrate the well-described expression changes of transcription factors and their actions, as revealed in mutants, in the formation of SGNs and OC in the correct position and orientation with suitable innervation. Understanding the molecular basis of these developmental changes leading to the formation of the mammalian OC and highlighting the gaps in our knowledge might guide in vivo attempts to regenerate this most complicated cellular mosaic of the mammalian body for the reconstitution of hearing in a rapidly growing population of aging people suffering from hearing loss.

Whole Exome Sequencing and Heterologous Cellular Electrophysiology Studies Elucidate a Novel Loss-of-Function Mutation in the CACNA1A-Encoded Neuronal P/Q-Type Calcium Channel in a Child With Congenital Hypotonia and Developmental Delay.

PubMed

Weyhrauch, Derek L; Ye, Dan; Boczek, Nicole J; Tester, David J; Gavrilova, Ralitza H; Patterson, Marc C; Wieben, Eric D; Ackerman, Michael J

2016-02-01

A 4-year-old boy born at 37 weeks' gestation with intrauterine growth retardation presented with developmental delay with pronounced language and gross motor delay, axial hypotonia, and dynamic hypertonia of the extremities. Investigations including the Minnesota Newborn Screen, thyroid stimulating hormone/thyroxin, and inborn errors of metabolism screening were negative. Cerebral magnetic resonance imaging and spectroscopy were normal. Genetic testing was negative for coagulopathy, Smith-Lemli-Opitz, fragile X, and Prader-Willi/Angelman syndromes. Whole genome array analysis was unremarkable. Whole exome sequencing was performed through a commercial testing laboratory to elucidate the underlying etiology for the child's presentation. A de novo mutation was hypothesized. In attempt to establish pathogenicity of our candidate variant, cellular electrophysiologic functional analysis of the putative de novo mutation was performed using patch-clamp technology. Whole exome sequencing revealed a p.P1353L variant in the CACNA1A gene, which encodes for the α1-subunit of the brain-specific P/Q-type calcium channel (CaV2.1). This presynaptic high-voltage-gated channel couples neuronal excitation to the vesicular release of neurotransmitter and is implicated in several neurologic disorders. DNA Sanger sequencing confirmed that the de novo mutation was absent in both parents and present in the child only. Electrophysiologic analysis of P1353L-CACNA1A demonstrated near complete loss of function, with a 95% reduction in peak current density. Whole exome sequencing coupled with cellular electrophysiologic functional analysis of a de novoCACNA1A missense mutation has elucidated the probable underlying pathophysiologic mechanism responsible for the child's phenotype. Genetic testing of CACNA1A in patients with congenital hypotonia and developmental delay may be warranted. Copyright © 2016. Published by Elsevier Inc.

Ground Testing of the EMCS Seed Cassette for Biocompatibility with the Cellular Slime Mold, Dictyostelium Discoideum

NASA Technical Reports Server (NTRS)

Hanely, Julia C.; Reinsch, Sigrid; Myers, Zachary A.; Freeman, John; Steele, Marianne K.; Sun, Gwo-Shing; Heathcote, David G.

2014-01-01

The European Modular Cultivation System, EMCS, was developed by ESA for plant experiments. To expand the use of flight verified hardware for various model organisms, we performed ground experiments to determine whether ARC EMCS Seed Cassettes could be adapted for use with cellular slime mold for future space flight experiments. Dictyostelium is a cellular slime mold that can exist both as a single-celled independent organism and as a part of a multicellular colony which functions as a unit (pseudoplasmodium). Under certain stress conditions, individual amoebae will aggregate to form multicellular structures. Developmental pathways are very similar to those found in Eukaryotic organisms, making this a uniquely interesting organism for use in genetic studies. Dictyostelium has been used as a genetic model organism for prior space flight experiments. Due to the formation of spores that are resistant to unfavorable conditions such as desiccation, Dictyostelium is also a good candidate for use in the EMCS Seed Cassettes. The growth substratum in the cassettes is a gridded polyether sulfone (PES) membrane. A blotter beneath the PES membranes contains dried growth medium. The goals of this study were to (1) verify that Dictyostelium are capable of normal growth and development on PES membranes, (2) develop a method for dehydration of Dictyostelium spores with successful recovery and development after rehydration, and (3) successful mock rehydration experiments in cassettes. Our results show normal developmental progression in two strains of Dictyostelium discoideum on PES membranes with a bacterial food source. We have successfully performed a mock rehydration of spores with developmental progression from aggregation to slug formation, and production of morphologically normal spores within 9 days of rehydration. Our results indicate that experiments on the ISS using the slime mold, Dictyostelium discoideum could potentially be performed in the flight verified hardware of the EMCS ARC Seed Cassettes.

Physiology and Endocrinology Symposium: influence of cattle genotype (Bos indicus vs. Bos taurus) on oocyte and preimplantation embryo resistance to increased temperature.

PubMed

Paula-Lopes, F F; Lima, R S; Satrapa, R A; Barros, C M

2013-03-01

High environmental temperatures during the hot months of the year reduce reproductive performance in cattle. Summer heat stress depression in fertility is a multifactorial problem; however, there is evidence that the bovine germinal vesicle and maturing oocyte, as well as the early embryo, are major targets of the deleterious effects of heat stress. Such adverse effects are less pronounced in heat-tolerant breeds (Bos indicus) than heat-sensitive breeds (Bos taurus). This genetic variation results from the greater thermoregulatory ability and cellular thermoresistance of heat-tolerant breeds. Heat-induced oocyte cellular damage occurs in both cytoplasmic and nuclear compartments. Heat shock has been shown to reduce oocyte nuclear maturation, induce apoptosis, compromise oocyte cytoskeleton, and impair oocyte mitochondrial function and developmental competence. However, the oocyte cytoplasm is more susceptible to heat shock than the nucleus. This effect is greater for Bos taurus than Bos indicus oocytes. The detrimental effects of heat shock are also critical during the first cleavage divisions when most of the embryonic genome is inactive; however, the bovine embryo becomes more resistant to increased temperature as it proceeds through development. Several studies demonstrated that Bos indicus embryos are more thermotolerant than Bos taurus embryos. Adaptive changes involved in acquisition of thermotolerance are likely derived from changes in gene expression and (or) activity of biochemical molecules that control cellular functions against stress. Recently, molecules such as IGF-I and caspase inhibitor z-DEVD-fmk have been shown to exert a thermoprotective role, rescuing heat-induced oocyte and embryo cellular damage and developmental competence. Therefore, cattle genotype and thermoprotective molecules can be considered as an alternative to modulate the effects of increased temperature in reproductive function.

Cell migration, intercalation and growth regulate mammalian cochlear extension.

PubMed

Driver, Elizabeth Carroll; Northrop, Amy; Kelley, Matthew W

2017-10-15

Developmental remodeling of the sensory epithelium of the cochlea is required for the formation of an elongated, tonotopically organized auditory organ, but the cellular processes that mediate these events are largely unknown. We used both morphological assessments of cellular rearrangements and time-lapse imaging to visualize cochlear remodeling in mouse. Analysis of cell redistribution showed that the cochlea extends through a combination of radial intercalation and cell growth. Live imaging demonstrated that concomitant cellular intercalation results in a brief period of epithelial convergence, although subsequent changes in cell size lead to medial-lateral spreading. Supporting cells, which retain contact with the basement membrane, exhibit biased protrusive activity and directed movement along the axis of extension. By contrast, hair cells lose contact with the basement membrane, but contribute to continued outgrowth through increased cell size. Regulation of cellular protrusions, movement and intercalation within the cochlea all require myosin II. These results establish, for the first time, many of the cellular processes that drive the distribution of sensory cells along the tonotopic axis of the cochlea. © 2017. Published by The Company of Biologists Ltd.

Light-regulated leaf expansion in two Populus species: dependence on developmentally controlled ion transport.

PubMed

Stiles, Kari A; Van Volkenburgh, Elizabeth

2002-07-01

Leaf growth responses to light have been compared in two species of Populus, P. deltoides and P. trichocarpa. These species differ markedly in morphology, anatomy, and dependence on light during leaf expansion. Light stimulates the growth rate and acidification of cell walls in P. trichocarpa but not in P. deltoides, whereas leaves of P. deltoides maintain growth in the dark. Light-induced growth is promoted in P. deltoides when cells are provided 50-100 mM KCl. In both species, light initially depolarizes, then hyperpolarizes mesophyll plasma membranes. However, in the dark, the resting E(m) of mesophyll cells in P. deltoides, but not in P. trichocarpa, is relatively insensitive to decade changes in external [K+]. Results suggest that light-stimulated leaf growth depends on developmentally regulated cellular mechanisms controlling ion fluxes across the plasma membrane. These developmental differences underlie species-level differences in growth and physiological responses to the photoenvironment.

[Effect of human oviductal embryotrophic factors on gene expression of mouse preimplantation embryos].

PubMed

Yao, Yuan-Qing; Lee, Kai-Fai; Xu, Jia-Seng; Ho, Pak-Chung; Yeung, Shu-Biu

2007-09-01

To investigate the effect of embryotrophic factors (ETF) from human oviductal cells on gene expression of mouse early developmental embryos and discuss the role of fallopian tube in early development of embryos. ETF was isolated from conditioned medium of human oviductal cell line by sequential liquid chromatographic systems. Mouse embryos were treated by ETF in vitro. Using differential display RT-PCR, the gene expression of embryos treated by ETF was compared with embryos without ETF treatment. The differentially expressed genes were separated, re-amplified, cloned and sequenced. Gene expression profiles of embryos with ETF treatment was different from embryos without this treatment. Eight differentially expressed genes were cloned and sequenced. These genes functioned in RNA degradation, synthesis, splicing, protein trafficking, cellular differentiation and embryo development. Embryotrophic factors from human oviductal cells affect gene expression of early developmental embryos. The human oviductal cells play wide roles in early developmental stages of embryos.

45 CFR 1386.20 - Designated State Protection and Advocacy agency.

Code of Federal Regulations, 2012 CFR

2012-10-01

... DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM FORMULA GRANT PROGRAMS State System for Protection and Advocacy of the Rights of Individuals with Developmental Disabilities § 1386.20 Designated State Protection... 45 Public Welfare 4 2012-10-01 2012-10-01 false Designated State Protection and Advocacy agency...

45 CFR 1386.20 - Designated State Protection and Advocacy agency.

Code of Federal Regulations, 2013 CFR

2013-10-01

... DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM FORMULA GRANT PROGRAMS State System for Protection and Advocacy of the Rights of Individuals with Developmental Disabilities § 1386.20 Designated State Protection... 45 Public Welfare 4 2013-10-01 2013-10-01 false Designated State Protection and Advocacy agency...

45 CFR 1386.20 - Designated State Protection and Advocacy agency.

Code of Federal Regulations, 2011 CFR

2011-10-01

... DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM FORMULA GRANT PROGRAMS State System for Protection and Advocacy of the Rights of Individuals with Developmental Disabilities § 1386.20 Designated State Protection... 45 Public Welfare 4 2011-10-01 2011-10-01 false Designated State Protection and Advocacy agency...

45 CFR 1386.20 - Designated State Protection and Advocacy agency.

Code of Federal Regulations, 2014 CFR

2014-10-01

... DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM FORMULA GRANT PROGRAMS State System for Protection and Advocacy of the Rights of Individuals with Developmental Disabilities § 1386.20 Designated State Protection... 45 Public Welfare 4 2014-10-01 2014-10-01 false Designated State Protection and Advocacy agency...

Developmental retardation, reduced fecundity, and modulated expression of the defensome in the intertidal copepod Tigriopus japonicus exposed to BDE-47 and PFOS.

PubMed

Han, Jeonghoon; Won, Eun-Ji; Lee, Min-Chul; Seo, Jung Soo; Lee, Su-Jae; Lee, Jae-Seong

2015-08-01

2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and perfluorooctane sulfonate (PFOS) are widely dispersed persistent organic pollutants (POPs) in the marine ecosystem. However, their toxic effects on marine organisms are still poorly understood. In this study, we investigated the effects of BDE-47 and PFOS on development and reproduction at the organismal level and reactive oxygen species (ROS) production and gene expression patterns of the defensome at the cellular level in the intertidal copepod Tigriopus japonicus. In copepods exposed to BDE-47 and PFOS, we observed developmental retardation and reduced fecundity, suggesting repercussions on in vivo endpoints through alterations to the normal molting and reproduction system of T. japonicus. BDE-47 and PFOS increased levels of ROS in T. japonicus in a concentration-dependent manner, indicating that POPs can induce oxidative stress through the generation of ROS. Additionally, transcript profiles of genes related to detoxification (e.g., CYPs), antioxidant functions (e.g., GST- sigma, catalase, MnSOD), apoptosis (e.g., p53, Rb), and cellular proliferation (e.g., PCNA) were modulated over 72h in response to BDE-47 (120μg/L) and PFOS (1000μg/L). These findings indicate that BDE-47 and PFOS can induce oxidative stress-mediated DNA damage repair systems with transcriptional regulation of detoxification, antioxidant, and apoptosis-related genes, resulting in developmental retardation and reduced fecundity in the copepod T. japonicus. Copyright © 2015 Elsevier B.V. All rights reserved.

Stage-specific apoptosis, developmental delay, and embryonic lethality in mice homozygous for a targeted disruption in the murine Bloom's syndrome gene.

PubMed

Chester, N; Kuo, F; Kozak, C; O'Hara, C D; Leder, P

1998-11-01

Bloom's syndrome is a human autosomal genetic disorder characterized at the cellular level by genome instability and increased sister chomatid exchanges (SCEs). Clinical features of the disease include proportional dwarfism and a predisposition to develop a wide variety of malignancies. The human BLM gene has been cloned recently and encodes a DNA helicase. Mouse embryos homozygous for a targeted mutation in the murine Bloom's syndrome gene (Blm) are developmentally delayed and die by embryonic day 13.5. The fact that the interrupted gene is the homolog of the human BLM gene was confirmed by its homologous sequence, its chromosomal location, and by demonstrating high numbers of SCEs in cultured murine Blm-/- fibroblasts. The proportional dwarfism seen in the human is consistent with the small size and developmental delay (12-24 hr) seen during mid-gestation in murine Blm-/- embryos. Interestingly, the growth retardation in mutant embryos can be accounted for by a wave of increased apoptosis in the epiblast restricted to early post-implantation embryogenesis. Mutant embryos do not survive past day 13.5, and at this time exhibit severe anemia. Red blood cells and their precursors from Blm-/- embryos are heterogeneous in appearance and have increased numbers of macrocytes and micronuclei. Both the apoptotic wave and the appearance of micronuclei in red blood cells are likely cellular consequences of damaged DNA caused by effects on replicating or segregating chromosomes.

Friendship group identification, multidimensional self-concept, and experience of developmental tasks in adolescence.

PubMed

Tarrant, Mark; MacKenzie, Liam; Hewitt, Lisa A

2006-08-01

This study applied a social identity perspective to the study of adolescent self-concept and social development. British adolescents aged 14-15 years (N=114) completed a questionnaire which asked them to: (i) rate their degree of identification with a school-based friendship group; (ii) complete a measure of multi-dimensional self-concept; and (iii) report their experiences of a variety of personal, relational and socio-institutional (e.g., achieving economic independence) developmental tasks. Compared to low identifiers, participants who were highly identified with a friendship group reported highest levels of self-esteem; and these differences were most marked in non-academic domains of self. High identifiers also displayed higher levels of general self-esteem and reported more positive experiences of personal and relational developmental tasks. The discussion focuses on the potential benefits to understanding of social developmental processes that can be derived from a consideration of adolescents' subjective appraisals of their peer relations.

Trajectories of risk for early sexual activity and early substance use in the Fast Track prevention program.

PubMed

2014-02-01

Children who exhibit early-starting conduct problems are more likely than their peers to initiate sexual activity and substance use at an early age, experience pregnancy, and contract a sexually-transmitted disease [STD], placing them at risk for HIV/AIDS. Hence, understanding the development of multi-problem profiles among youth with early-starting conduct problems may benefit the design of prevention programs. In this study, 1,199 kindergarten children (51% African American; 47% European American; 69% boys) over-sampled for high rates of aggressive-disruptive behavior problems were followed through age 18. Latent class analyses (LCA) were used to define developmental profiles associated with the timing of initiation of sexual activity, tobacco and alcohol/drug use and indicators of risky adolescent sex (e.g. pregnancy and STD). Half of the high-risk children were randomized to a multi-component preventive intervention (Fast Track). The intervention did not significantly reduce membership in the classes characterized by risky sex practices. However, additional analyses examined predictors of poor outcomes, which may inform future prevention efforts.

The Benefits of Multi-Year Research Experiences: Differences in Novice and Experienced Students’ Reported Gains from Undergraduate Research

PubMed Central

Thiry, Heather; Weston, Timothy J.; Laursen, Sandra L.; Hunter, Anne-Barrie

2012-01-01

This mixed-methods study explores differences in novice and experienced undergraduate students’ perceptions of their cognitive, personal, and professional gains from engaging in scientific research. The study was conducted in four different undergraduate research (UR) programs at two research-extensive universities; three of these programs had a focus on the biosciences. Seventy-three entry-level and experienced student researchers participated in in-depth, semi-structured interviews and completed the quantitative Undergraduate Research Student Self-Assessment (URSSA) instrument. Interviews and surveys assessed students’ developmental outcomes from engaging in UR. Experienced students reported distinct personal, professional, and cognitive outcomes relative to their novice peers, including a more sophisticated understanding of the process of scientific research. Students also described the trajectories by which they developed not only the intellectual skills necessary to advance in science, but also the behaviors and temperament necessary to be a scientist. The findings suggest that students benefit from multi-year UR experiences. Implications for UR program design, advising practices, and funding structures are discussed. PMID:22949423

47 CFR 2.803 - Marketing of radio frequency devices prior to equipment authorization.

Code of Federal Regulations, 2010 CFR

2010-10-01

... device that is in the conceptual, developmental, design or pre-production stage is permitted prior to... operation takes place at the manufacturer's facilities during developmental, design, or pre-production... development, design or pre-production stages. A product operated under this provision shall be labelled, in a...

47 CFR 2.803 - Marketing of radio frequency devices prior to equipment authorization.

Code of Federal Regulations, 2012 CFR

2012-10-01

... device that is in the conceptual, developmental, design or pre-production stage is permitted prior to... operation takes place at the manufacturer's facilities during developmental, design, or pre-production... development, design or pre-production stages. A product operated under this provision shall be labelled, in a...

47 CFR 2.803 - Marketing of radio frequency devices prior to equipment authorization.

Code of Federal Regulations, 2011 CFR

2011-10-01

... device that is in the conceptual, developmental, design or pre-production stage is permitted prior to... operation takes place at the manufacturer's facilities during developmental, design, or pre-production... development, design or pre-production stages. A product operated under this provision shall be labelled, in a...

Cellular Auxin Homeostasis under High Temperature Is Regulated through a SORTING NEXIN1–Dependent Endosomal Trafficking Pathway[C][W

PubMed Central

Hanzawa, Taiki; Shibasaki, Kyohei; Numata, Takahiro; Kawamura, Yukio; Gaude, Thierry; Rahman, Abidur

2013-01-01

High-temperature-mediated adaptation in plant architecture is linked to the increased synthesis of the phytohormone auxin, which alters cellular auxin homeostasis. The auxin gradient, modulated by cellular auxin homeostasis, plays an important role in regulating the developmental fate of plant organs. Although the signaling mechanism that integrates auxin and high temperature is relatively well understood, the cellular auxin homeostasis mechanism under high temperature is largely unknown. Using the Arabidopsis thaliana root as a model, we demonstrate that under high temperature, roots counterbalance the elevated level of intracellular auxin by promoting shootward auxin efflux in a PIN-FORMED2 (PIN2)-dependent manner. Further analyses revealed that high temperature selectively promotes the retrieval of PIN2 from late endosomes and sorts them to the plasma membrane through an endosomal trafficking pathway dependent on SORTING NEXIN1. Our results demonstrate that recycling endosomal pathway plays an important role in facilitating plants adaptation to increased temperature. PMID:24003052

Embryological Development: Evolutionary History, Genetic Bias, and Cellular Environment Control the Flow of Developmental Events. Part I.

ERIC Educational Resources Information Center

Caplan, Arnold I.

1981-01-01

Describes development of the limb and various interactions necessary for the expression of its unique form and phenotypes to uncover the hierarchical controlling steps in the development process for the potential of avoiding abnormal events and manipulating what might be detrimental genetic events into a normal sequence. (Author/SK)

Causal Inferences from Mining ToxCast Data and the Biomedical Literature for Molecular Pathways and Cellular Processes in Cleft Palate (SOT)

EPA Science Inventory

Sixty-five chemicals in the ToxCast high-throughput screening (HTS) dataset have been linked to cleft palate based on data from ToxRefDB (rat or rabbit prenatal developmental toxicity studies) or from literature reports. These compounds are structurally diverse and thus likely to...

PROLIFERATION AS A KEY EVENT IN DEVELOPMENTAL TOXICITY: "CHEMICAL SCREENING IN HUMAN NEURAL STEM CELLS USING HIGH CONTENT IMAGING

EPA Science Inventory

New toxicity testing approaches will rely on in vitro assays to assess chemical effects at the cellular and molecular level. Cell proliferation is imperative to normal development, and chemical disruption of this process can be detrimental to the organism. As part of an effort to...

Contributions of immune responses to developmental resistance in Lymantria dispar challenged with baculovirus

Treesearch

James McNeil; Diana Cox-Foster; James Slavicek; Kelli Hoover

2010-01-01

How the innate immune system functions to defend insects from viruses is an emerging field of study. We examined the impact of melanized encapsulation, a component of innate immunity that integrates both cellular and humoral immune responses, on the success of the baculovirus Lymantria dispar multiple nucleocapsid nucleopolyhedrovirus (LdMNPV) in its...

Reliability of Eye Tracking and Pupillometry Measures in Individuals with Fragile X Syndrome

ERIC Educational Resources Information Center

Farzin, Faraz; Scaggs, Felicia; Hervey, Crystal; Berry-Kravis, Elizabeth; Hessl, David

2011-01-01

Recent insight into the underlying molecular and cellular mechanisms of fragile X syndrome (FXS) has led to the proposal and development of new pharmaceutical treatment strategies, and the initiation of clinical trials aimed at correcting core symptoms of the developmental disorder. Consequently, there is an urgent and critical need for outcome…

UV-B COMPONENT OF SUNLIGHT CAUSES MEASURABLE DAMAGE IN FIELD-GROWN MAIZE (ZEA MAYS L.): DEVELOPMENTAL AND CELLULAR HETEROGENEITY OF DAMAGE AND REPAIR. (R824900)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Caenorhabditis elegans utilizes dauer pheromone biosynthesis to dispose of toxic peroxisomal fatty acids for cellular homoeostasis

USDA-ARS?s Scientific Manuscript database

Caenorhabditis elegans secretes a dauer pheromone or daumone composed of ascarylose and a fatty acid side chain, perception of which enables worms to gauge depletion of food or a high worm population density. As a result, worms enter the dauer state, a specific developmental stage capable of surviv...

Of Heart & Kidneys: Hands-On Activities for Demonstrating Organ Function & Repair

ERIC Educational Resources Information Center

Kao, Robert M.

2014-01-01

A major challenge in teaching organ development and disease is deconstructing a complex choreography of molecular and cellular changes over time into a linear stepwise process for students. As an entry toward learning developmental concepts, I propose two inexpensive hands-on activities to help facilitate learning of (1) how to identify defects in…

Trafficking to the Apical and Basolateral Membranes in Polarized Epithelial Cells

PubMed Central

Stoops, Emily H.

2014-01-01

Renal epithelial cells must maintain distinct protein compositions in their apical and basolateral membranes in order to perform their transport functions. The creation of these polarized protein distributions depends on sorting signals that designate the trafficking route and site of ultimate functional residence for each protein. Segregation of newly synthesized apical and basolateral proteins into distinct carrier vesicles can occur at the trans-Golgi network, recycling endosomes, or a growing assortment of stations along the cellular trafficking pathway. The nature of the specific sorting signal and the mechanism through which it is interpreted can influence the route a protein takes through the cell. Cell type–specific variations in the targeting motifs of a protein, as are evident for Na,K-ATPase, demonstrate a remarkable capacity to adapt sorting pathways to different developmental states or physiologic requirements. This review summarizes our current understanding of apical and basolateral trafficking routes in polarized epithelial cells. PMID:24652803

Rbm20-deficient cardiogenesis reveals early disruption of RNA processing and sarcomere remodeling establishing a developmental etiology for dilated cardiomyopathy.

PubMed

Beraldi, Rosanna; Li, Xing; Martinez Fernandez, Almudena; Reyes, Santiago; Secreto, Frank; Terzic, Andre; Olson, Timothy M; Nelson, Timothy J

2014-07-15

Dilated cardiomyopathy (DCM) due to mutations in RBM20, a gene encoding an RNA-binding protein, is associated with high familial penetrance, risk of progressive heart failure and sudden death. Although genetic investigations and physiological models have established the linkage of RBM20 with early-onset DCM, the underlying basis of cellular and molecular dysfunction is undetermined. Modeling human genetics using a high-throughput pluripotent stem cell platform was herein designed to pinpoint the initial transcriptome dysfunction and mechanistic corruption in disease pathogenesis. Tnnt2-pGreenZeo pluripotent stem cells were engineered to knockdown Rbm20 (shRbm20) to determine the cardiac-pathogenic phenotype during cardiac differentiation. Intracellular Ca(2+) transients revealed Rbm20-dependent alteration in Ca(2+) handling, coinciding with known pathological splice variants of Titin and Camk2d genes by Day 24 of cardiogenesis. Ultrastructural analysis demonstrated elongated and thinner sarcomeres in the absence of Rbm20 that is consistent with human cardiac biopsy samples. Furthermore, Rbm20-depleted transcriptional profiling at Day 12 identified Rbm20-dependent dysregulation with 76% of differentially expressed genes linked to known cardiac pathology ranging from primordial Nkx2.5 to mature cardiac Tnnt2 as the initial molecular aberrations. Notably, downstream consequences of Rbm20-depletion at Day 24 of differentiation demonstrated significant dysregulation of extracellular matrix components such as the anomalous overexpression of the Vtn gene. By using the pluripotent stem cell platform to model human cardiac disease according to a stage-specific cardiogenic roadmap, we established a new paradigm of familial DCM pathogenesis as a developmental disorder that is patterned during early cardiogenesis and propagated with cellular mechanisms of pathological cardiac remodeling. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Developmental Summer Bridge Programs. What Works Clearinghouse™ Intervention Report

ERIC Educational Resources Information Center

What Works Clearinghouse, 2015

2015-01-01

Developmental summer bridge programs are designed to reduce the need for developmental education in college by providing students with accelerated instruction in areas where additional knowledge and skills are needed to help them succeed in higher education. The WWC identified one study of developmental summer bridge programs that meets WWC…

High Content Analysis of Hippocampal Neuron-Astrocyte Co-cultures Shows a Positive Effect of Fortasyn Connect on Neuronal Survival and Postsynaptic Maturation.

PubMed

van Deijk, Anne-Lieke F; Broersen, Laus M; Verkuyl, J Martin; Smit, August B; Verheijen, Mark H G

2017-01-01

Neuronal and synaptic membranes are composed of a phospholipid bilayer. Supplementation with dietary precursors for phospholipid synthesis -docosahexaenoic acid (DHA), uridine and choline- has been shown to increase neurite outgrowth and synaptogenesis both in vivo and in vitro . A role for multi-nutrient intervention with specific precursors and cofactors has recently emerged in early Alzheimer's disease, which is characterized by decreased synapse numbers in the hippocampus. Moreover, the medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect (FC), improves memory performance in early Alzheimer's disease patients, possibly via maintaining brain connectivity. This suggests an effect of FC on synapses, but the underlying cellular mechanism is not fully understood. Therefore, we investigated the effect of FC (consisting of DHA, eicosapentaenoic acid (EPA), uridine, choline, phospholipids, folic acid, vitamins B12, B6, C and E, and selenium), on synaptogenesis by supplementing it to primary neuron-astrocyte co-cultures, a cellular model that mimics metabolic dependencies in the brain. We measured neuronal developmental processes using high content screening in an automated manner, including neuronal survival, neurite morphology, as well as the formation and maturation of synapses. Here, we show that FC supplementation resulted in increased numbers of neurons without affecting astrocyte number. Furthermore, FC increased postsynaptic PSD95 levels in both immature and mature synapses. These findings suggest that supplementation with FC to neuron-astrocyte co-cultures increased both neuronal survival and the maturation of postsynaptic terminals, which might aid the functional interpretation of FC-based intervention strategies in neurological diseases characterized by neuronal loss and impaired synaptic functioning.

High Content Analysis of Hippocampal Neuron-Astrocyte Co-cultures Shows a Positive Effect of Fortasyn Connect on Neuronal Survival and Postsynaptic Maturation

PubMed Central

van Deijk, Anne-Lieke F.; Broersen, Laus M.; Verkuyl, J. Martin; Smit, August B.; Verheijen, Mark H. G.

2017-01-01

Neuronal and synaptic membranes are composed of a phospholipid bilayer. Supplementation with dietary precursors for phospholipid synthesis –docosahexaenoic acid (DHA), uridine and choline– has been shown to increase neurite outgrowth and synaptogenesis both in vivo and in vitro. A role for multi-nutrient intervention with specific precursors and cofactors has recently emerged in early Alzheimer's disease, which is characterized by decreased synapse numbers in the hippocampus. Moreover, the medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect (FC), improves memory performance in early Alzheimer's disease patients, possibly via maintaining brain connectivity. This suggests an effect of FC on synapses, but the underlying cellular mechanism is not fully understood. Therefore, we investigated the effect of FC (consisting of DHA, eicosapentaenoic acid (EPA), uridine, choline, phospholipids, folic acid, vitamins B12, B6, C and E, and selenium), on synaptogenesis by supplementing it to primary neuron-astrocyte co-cultures, a cellular model that mimics metabolic dependencies in the brain. We measured neuronal developmental processes using high content screening in an automated manner, including neuronal survival, neurite morphology, as well as the formation and maturation of synapses. Here, we show that FC supplementation resulted in increased numbers of neurons without affecting astrocyte number. Furthermore, FC increased postsynaptic PSD95 levels in both immature and mature synapses. These findings suggest that supplementation with FC to neuron-astrocyte co-cultures increased both neuronal survival and the maturation of postsynaptic terminals, which might aid the functional interpretation of FC-based intervention strategies in neurological diseases characterized by neuronal loss and impaired synaptic functioning. PMID:28824363

[Fanconi anemia: cellular and molecular features].

PubMed

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

2007-02-01

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

Community College Facility Design: The Relationship between the Learning-Centered Paradigm and Learning Space as Viewed through the Lens of Developmental Studies Faculty

ERIC Educational Resources Information Center

Perkinson, Betty J.

2009-01-01

The view that community college developmental studies educators have about the space in which they teach, any renovated or new spaces they were involved in designing, and the type of space in which they would like to teach is examined. The developmental studies educators are experts in their field, having completed The Kellogg Institute at…

A public health framework to translate risk factors related to political violence and war into multi-level preventive interventions.

PubMed

De Jong, Joop T V M

2010-01-01

Political violence, armed conflicts and human rights violations are produced by a variety of political, economic and socio-cultural factors. Conflicts can be analyzed with an interdisciplinary approach to obtain a global understanding of the relative contribution of risk and protective factors. A public health framework was designed to address these risk factors and protective factors. The framework resulted in a matrix that combined primary, secondary and tertiary interventions with their implementation on the levels of the society-at-large, the community, and the family and individual. Subsequently, the risk and protective factors were translated into multi-sectoral, multi-modal and multi-level preventive interventions involving the economy, governance, diplomacy, the military, human rights, agriculture, health, and education. Then the interventions were slotted in their appropriate place in the matrix. The interventions can be applied in an integrative form by international agencies, governments and non-governmental organizations, and molded to meet the requirements of the historic, political-economic and socio-cultural context. The framework maps the complementary fit among the different actors while engaging themselves in preventive, rehabilitative and reconstructive interventions. The framework shows how the economic, diplomatic, political, criminal justice, human rights, military, health and rural development sectors can collaborate to promote peace or prevent the aggravation or continuation of violence. A deeper understanding of the association between risk and protective factors and the developmental pathways of generic, country-specific and culture-specific factors leading to political violence is needed.

Smart repeater system for communications interoperability during multiagency law enforcement operations

NASA Astrophysics Data System (ADS)

Crutcher, Richard I.; Jones, R. W.; Moore, Michael R.; Smith, S. F.; Tolley, Alan L.; Rochelle, Robert W.

1997-02-01

A prototype 'smart' repeater that provides interoperability capabilities for radio communication systems in multi-agency and multi-user scenarios is being developed by the Oak Ridge National Laboratory. The smart repeater functions as a deployable communications platform that can be dynamically reconfigured to cross-link the radios of participating federal, state, and local government agencies. This interconnection capability improves the coordination and execution of multi-agency operations, including coordinated law enforcement activities and general emergency or disaster response scenarios. The repeater provides multiple channels of operation in the 30-50, 118-136, 138-174, and 403-512 MHz land mobile communications and aircraft bands while providing the ability to cross-connect among multiple frequencies, bands, modulation types, and encryption formats. Additionally, two telephone interconnects provide links to the fixed and cellular telephone networks. The 800- and 900-MHz bands are not supported by the prototype, but the modular design of the system accommodates future retrofits to extend frequency capabilities with minimal impact to the system. Configuration of the repeater is through a portable personal computer with a Windows-based graphical interface control screen that provides dynamic reconfiguration of network interconnections and formats.

Attractor Structures of Signaling Networks: Consequences of Different Conformational Barcode Dynamics and Their Relations to Network-Based Drug Design.

PubMed

Szalay, Kristóf Z; Nussinov, Ruth; Csermely, Peter

2014-06-01

Conformational barcodes tag functional sites of proteins and are decoded by interacting molecules transmitting the incoming signal. Conformational barcodes are modified by all co-occurring allosteric events induced by post-translational modifications, pathogen, drug binding, etc. We argue that fuzziness (plasticity) of conformational barcodes may be increased by disordered protein structures, by integrative plasticity of multi-phosphorylation events, by increased intracellular water content (decreased molecular crowding) and by increased action of molecular chaperones. This leads to increased plasticity of signaling and cellular networks. Increased plasticity is both substantiated by and inducing an increased noise level. Using the versatile network dynamics tool, Turbine (www.turbine.linkgroup.hu), here we show that the 10 % noise level expected in cellular systems shifts a cancer-related signaling network of human cells from its proliferative attractors to its largest, apoptotic attractor representing their health-preserving response in the carcinogen containing and tumor suppressor deficient environment modeled in our study. Thus, fuzzy conformational barcodes may not only make the cellular system more plastic, and therefore more adaptable, but may also stabilize the complex system allowing better access to its largest attractor. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Developmental and light regulation of tumor suppressor protein PP2A in the retina

PubMed Central

Rajala, Ammaji; Wang, Yuhong; Abcouwer, Steven F.; Gardner, Thomas W.; Rajala, Raju V.S.

2018-01-01

Protein phosphatases are a group of universal enzymes that are responsible for the dephosphorylation of various proteins and enzymes in cells. Cellular signal transduction events are largely governed by the phosphorylation of key proteins. The length of cellular response depends on the activation of protein phosphatase that dephosphorylates the phosphate groups to halt a biological response, and fine-tune the defined cellular outcome. Dysregulation of these phosphatase(s) results in various disease phenotypes. The retina is a post-mitotic tissue, and oncogenic tyrosine and serine/ threonine kinase activities are important for retinal neuron survival. Aberrant activation of protein phosphatase(s) may have a negative effect on retinal neurons. In the current study, we characterized tumor suppressor protein phosphatase 2 (PP2A), a major serine/ threonine kinase with a broad substrate specificity. Our data suggest that PP2A is developmentally regulated in the retina, localized predominantly in the inner retina, and expressed in photoreceptor inner segments. Our findings indicate that PKCα and mTOR may serve as PP2A substrates. We found that light regulates PP2A activity. Our studies also suggest that rhodopsin regulates PP2A and its substrate(s) dephosphorylation. PP2A substrate phosphorylation is increased in mice lacking the A-subunit of PP2A. However, there is no accompanying effect on retina structure and function. Together, our findings suggest that controlling the activity of PP2A in the retina may be neuroprotective. PMID:29416710

Imaging Cell Shape Change in Living Drosophila Embryos

PubMed Central

Figard, Lauren; Sokac, Anna Marie

2011-01-01

The developing Drosophila melanogaster embryo undergoes a number of cell shape changes that are highly amenable to live confocal imaging. Cell shape changes in the fly are analogous to those in higher organisms, and they drive tissue morphogenesis. So, in many cases, their study has direct implications for understanding human disease (Table 1)1-5. On the sub-cellular scale, these cell shape changes are the product of activities ranging from gene expression to signal transduction, cell polarity, cytoskeletal remodeling and membrane trafficking. Thus, the Drosophila embryo provides not only the context to evaluate cell shape changes as they relate to tissue morphogenesis, but also offers a completely physiological environment to study the sub-cellular activities that shape cells. The protocol described here is designed to image a specific cell shape change called cellularization. Cellularization is a process of dramatic plasma membrane growth, and it ultimately converts the syncytial embryo into the cellular blastoderm. That is, at interphase of mitotic cycle 14, the plasma membrane simultaneously invaginates around each of ~6000 cortically anchored nuclei to generate a sheet of primary epithelial cells. Counter to previous suggestions, cellularization is not driven by Myosin-2 contractility6, but is instead fueled largely by exocytosis of membrane from internal stores7. Thus, cellularization is an excellent system for studying membrane trafficking during cell shape changes that require plasma membrane invagination or expansion, such as cytokinesis or transverse-tubule (T-tubule) morphogenesis in muscle. Note that this protocol is easily applied to the imaging of other cell shape changes in the fly embryo, and only requires slight adaptations such as changing the stage of embryo collection, or using "embryo glue" to mount the embryo in a specific orientation (Table 1)8-19. In all cases, the workflow is basically the same (Figure 1). Standard methods for cloning and Drosophila transgenesis are used to prepare stable fly stocks that express a protein of interest, fused to Green Fluorescent Protein (GFP) or its variants, and these flies provide a renewable source of embryos. Alternatively, fluorescent proteins/probes are directly introduced into fly embryos via straightforward micro-injection techniques9-10. Then, depending on the developmental event and cell shape change to be imaged, embryos are collected and staged by morphology on a dissecting microscope, and finally positioned and mounted for time-lapse imaging on a confocal microscope. PMID:21490577

Tetracapsuloides bryosalmonae infection affects the expression of genes involved in cellular signal transduction and iron metabolism in the kidney of the brown trout Salmo trutta.

PubMed

Kumar, Gokhlesh; Sarker, Subhodeep; Menanteau-Ledouble, Simon; El-Matbouli, Mansour

2015-06-01

Tetracapsuloides bryosalmonae is an enigmatic endoparasite which causes proliferative kidney disease in various species of salmonids in Europe and North America. The life cycle of the European strain of T. bryosalmonae generally completes in an invertebrate host freshwater bryozoan and vertebrate host brown trout (Salmo trutta) Linnaeus, 1758. Little is known about the gene expression in the kidney of brown trout during the developmental stages of T. bryosalmonae. In the present study, quantitative real-time PCR was applied to quantify the target genes of interest in the kidney of brown trout at different time points of T. bryosalmonae development. PCR primers specific for target genes were designed and optimized, and their gene expression levels were quantified in the cDNA kidney samples using SYBR Green Supermix. Expression of Rab GDP dissociation inhibitor beta, integral membrane protein 2B, NADH dehydrogenase 1 beta subcomplex subunit 6, and 26S protease regulatory subunit S10B were upregulated significantly in infected brown trout, while the expression of the ferritin M middle subunit was downregulated significantly. These results suggest that host genes involved in cellular signal transduction, proteasomal activities, including membrane transporters and cellular iron storage, are differentially upregulated or downregulated in the kidney of brown trout during parasite development. The gene expression pattern of infected renal tissue may support the development of intraluminal sporogonic stages of T. bryosalmonae in the renal tubular lumen of brown trout which may facilitate the release of viable parasite spores to transmit to the invertebrate host bryozoan.

Genome-scale prediction of proteins with long intrinsically disordered regions.

PubMed

Peng, Zhenling; Mizianty, Marcin J; Kurgan, Lukasz

2014-01-01

Proteins with long disordered regions (LDRs), defined as having 30 or more consecutive disordered residues, are abundant in eukaryotes, and these regions are recognized as a distinct class of biologically functional domains. LDRs facilitate various cellular functions and are important for target selection in structural genomics. Motivated by the lack of methods that directly predict proteins with LDRs, we designed Super-fast predictor of proteins with Long Intrinsically DisordERed regions (SLIDER). SLIDER utilizes logistic regression that takes an empirically chosen set of numerical features, which consider selected physicochemical properties of amino acids, sequence complexity, and amino acid composition, as its inputs. Empirical tests show that SLIDER offers competitive predictive performance combined with low computational cost. It outperforms, by at least a modest margin, a comprehensive set of modern disorder predictors (that can indirectly predict LDRs) and is 16 times faster compared to the best currently available disorder predictor. Utilizing our time-efficient predictor, we characterized abundance and functional roles of proteins with LDRs over 110 eukaryotic proteomes. Similar to related studies, we found that eukaryotes have many (on average 30.3%) proteins with LDRs with majority of proteomes having between 25 and 40%, where higher abundance is characteristic to proteomes that have larger proteins. Our first-of-its-kind large-scale functional analysis shows that these proteins are enriched in a number of cellular functions and processes including certain binding events, regulation of catalytic activities, cellular component organization, biogenesis, biological regulation, and some metabolic and developmental processes. A webserver that implements SLIDER is available at http://biomine.ece.ualberta.ca/SLIDER/. Copyright © 2013 Wiley Periodicals, Inc.

Multi-Material Tissue Engineering Scaffold with Hierarchical Pore Architecture.

PubMed

Morgan, Kathy Ye; Sklaviadis, Demetra; Tochka, Zachary L; Fischer, Kristin M; Hearon, Keith; Morgan, Thomas D; Langer, Robert; Freed, Lisa E

2016-08-23

Multi-material polymer scaffolds with multiscale pore architectures were characterized and tested with vascular and heart cells as part of a platform for replacing damaged heart muscle. Vascular and muscle scaffolds were constructed from a new material, poly(limonene thioether) (PLT32i), which met the design criteria of slow biodegradability, elastomeric mechanical properties, and facile processing. The vascular-parenchymal interface was a poly(glycerol sebacate) (PGS) porous membrane that met different criteria of rapid biodegradability, high oxygen permeance, and high porosity. A hierarchical architecture of primary (macroscale) and secondary (microscale) pores was created by casting the PLT32i prepolymer onto sintered spheres of poly(methyl methacrylate) (PMMA) within precisely patterned molds followed by photocuring, de-molding, and leaching out the PMMA. Pre-fabricated polymer templates were cellularized, assembled, and perfused in order to engineer spatially organized, contractile heart tissue. Structural and functional analyses showed that the primary pores guided heart cell alignment and enabled robust perfusion while the secondary pores increased heart cell retention and reduced polymer volume fraction.

Tumor angiogenesis assessment using multi-fluorescent scans on murine slices by Markov random field framework

NASA Astrophysics Data System (ADS)

Laifa, Oumeima; Le Guillou-Buffello, Delphine; Racoceanu, Daniel

2017-11-01

The fundamental role of vascular supply in tumor growth makes the evaluation of the angiogenesis crucial in assessing effect of anti-angiogenic therapies. Since many years, such therapies are designed to inhibit the vascular endothelial growth factor (VEGF). To contribute to the assessment of anti-angiogenic agent (Pazopanib) effect on vascular and cellular structures, we acquired data from tumors extracted from a murine tumor model using Multi- Fluorescence Scanning. In this paper, we implemented an unsupervised algorithm combining the Watershed segmentation and Markov Random Field model (MRF). This algorithm allowed us to quantify the proportion of apoptotic endothelial cells and to generate maps according to cell density. Stronger association between apoptosis and endothelial cells was revealed in the tumors receiving anti-angiogenic therapy (n = 4) as compared to those receiving placebo (n = 4). A high percentage of apoptotic cells in the tumor area are endothelial. Lower density cells were detected in tumor slices presenting higher apoptotic endothelial areas.

Real-time intravital microscopy of individual nanoparticle dynamics in liver and tumors of live mice

PubMed Central

van de Ven, Anne L; Kim, Pilhan; Ferrari, Mauro; Yun, Seok Hyun

2013-01-01

Intravital microscopy is emerging as an important experimental tool for the research and development of multi-functional therapeutic nanoconstructs. The direct visualization of nanoparticle dynamics within live animals provides invaluable insights into the mechanisms that regulate nanotherapeutics transport and cell-particle interactions. Here we present a protocol to image the dynamics of nanoparticles within the liver and tumors of live mice immediately following systemic injection using a high-speed (30-400 fps) confocal or multi-photon laser-scanning fluorescence microscope. Techniques for quantifying the real-time accumulation and cellular association of individual particles with a size ranging from several tens of nanometers to micrometers are described, as well as an experimental strategy for labeling Kupffer cells in the liver in vivo. Experimental design considerations and controls are provided, as well as minimum equipment requirements. The entire protocol takes approximately 4-8 hours and yields quantitative information. These techniques can serve to study a wide range of kinetic parameters that drive nanotherapeutics delivery, uptake, and treatment response. PMID:25383179

A multi-physics model for ultrasonically activated soft tissue.

PubMed

Suvranu De, Rahul

2017-02-01

A multi-physics model has been developed to investigate the effects of cellular level mechanisms on the thermomechanical response of ultrasonically activated soft tissue. Cellular level cavitation effects have been incorporated in the tissue level continuum model to accurately determine the thermodynamic states such as temperature and pressure. A viscoelastic material model is assumed for the macromechanical response of the tissue. The cavitation model based equation-of-state provides the additional pressure arising from evaporation of intracellular and cellular water by absorbing heat due to structural and viscoelastic heating in the tissue, and temperature to the continuum level thermomechanical model. The thermomechanical response of soft tissue is studied for the operational range of frequencies of oscillations and applied loads for typical ultrasonically activated surgical instruments. The model is shown to capture characteristics of ultrasonically activated soft tissue deformation and temperature evolution. At the cellular level, evaporation of water below the boiling temperature under ambient conditions is indicative of protein denaturation around the temperature threshold for coagulation of tissues. Further, with increasing operating frequency (or loading), the temperature rises faster leading to rapid evaporation of tissue cavity water, which may lead to accelerated protein denaturation and coagulation.

Principles for designing randomized preventive trials in mental health: an emerging developmental epidemiology paradigm.

PubMed

Brown, C H; Liao, J

1999-10-01

An emerging population-based paradigm is now being used to guide the design of preventive trials used to test developmental models. We discuss elements of the designs of several ongoing randomized preventive trials involving reduction of risk for children of divorce, for children who exhibit behavioral or learning problems, and for children whose parents are being treated for depression. To test developmental models using this paradigm, we introduce three classes of design issues: design for prerandomization, design for intervention, and design for postintervention. For each of these areas, we present quantitative results from power calculations. Both scientific and cost implications of these power calculations are discussed in terms of variation among subjects on preintervention measures, unit of intervention, assignment, balancing, number of pretest and posttest measures, and the examination of moderation effects.

14 CFR 1274.905 - Rights in data.

Code of Federal Regulations, 2013 CFR

2013-01-01

... research, experimental, developmental, engineering, demonstration, or design activities are to be carried... the agreement. If cost sharing is unequal or no extensive research, experimental, developmental, engineering, demonstration, or design activities are likely, a different set of provisions may be appropriate...

14 CFR 1274.905 - Rights in data.

Code of Federal Regulations, 2010 CFR

2010-01-01

... research, experimental, developmental, engineering, demonstration, or design activities are to be carried... the agreement. If cost sharing is unequal or no extensive research, experimental, developmental, engineering, demonstration, or design activities are likely, a different set of provisions may be appropriate...

A systematic study on hemocyte identification and plasma prophenoloxidase from Culex pipiens quinquefasciatus at different developmental stages.

PubMed

Wang, Zhixiang; Lu, Anrui; Li, Xuquan; Shao, Qimiao; Beerntsen, Brenda T; Liu, Chaoliang; Ma, Yajun; Huang, Yamin; Zhu, Huaimin; Ling, Erjun

2011-01-01

Culexpipiens quinquefasciatus (C. quinquefasciatus) is an important vector that can transmit human diseases such as West Nile virus, lymphatic filariasis, Japanese encephalitis and St. Louis encephalitis. However, very limited research concerning the humoral and cellular immune defenses of C. quinquefasciatus has been done. Here we present the research on hemocyte identification and plasma including hemocyte prophenoloxidase from C. quinquefasciatus at all developmental stages in order to obtain a complete picture of C. quinquefasciatus innate immunity. We identified hemocytes into four types: prohemocytes, oenocytoids, plasmatocytes and granulocytes. Prophenoloxidase (PPO) is an essential enzyme to induce melanization after encapsulation. PPO-positive hemocytes and plasma PPO were observed at all developmental stages. As for specific hemocyte types, prophenoloxidase was found in the plasmatocytes at larval stage alone and in the smallest prohemocytes during almost all developmental stages. Moreover, the granulocytes were PPO-positive from blood-fed female mosquitoes and oenocytoids were observed PPO-positive in pupae and in adult females after blood-feeding. As for plasma, there were different patterns of PPO in C. quinquefasciatus at different developmental stages. These results are forming a basis for further studies on the function of C. quinquefasciatus hemocytes and prophenoloxidase as well as their involvement in fighting against mosquito-borne pathogens. Copyright © 2010 Elsevier Inc. All rights reserved.

Development of multi-metal interaction model for Daphnia magna: Significance of metallothionein in cellular redistribution.

PubMed

Wang, Xiangrui; Liu, Jianyu; Tan, Qiaoguo; Ren, Jinqian; Liang, Dingyuan; Fan, Wenhong

2018-04-30

Despite the great progress made in metal-induced toxicity mechanisms, a critical knowledge gap still exists in predicting adverse effects of heavy metals on living organisms in the natural environment, particularly during exposure to multi-metals. In this study, a multi-metal interaction model of Daphnia manga was developed in an effort to provide reasonable explanations regarding the joint effects resulting from exposure to multi-metals. Metallothionein (MT), a widely used biomarker, was selected. In this model, MT was supposed to play the role of a crucial transfer protein rather than detoxifying protein. Therefore, competitive complexation of metals to MT could highly affect the cellular metal redistribution. Thus, competitive complexation of MT in D. magna with metals like Pb 2+ , Cd 2+ and Cu 2+ was qualitatively studied. The results suggested that Cd 2+ had the highest affinity towards MT, followed by Pb 2+ and Cu 2+ . On the other hand, the combination of MT with Cu 2+ appeared to alter its structure which resulted in higher affinity towards Pb 2+ . Overall, the predicted bioaccumulation of metals under multi-metal exposure was consisted with earlier reported studies. This model provided an alternative angle for joint effect through a combination of kinetic process and internal interactions, which could help to develop future models predicting toxicity to multi-metal exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

A surgical confocal microlaparoscope for real-time optical biopsies

NASA Astrophysics Data System (ADS)

Tanbakuchi, Anthony Amir

The first real-time fluorescence confocal microlaparoscope has been developed that provides instant in vivo cellular images, comparable to those provided by histology, through a nondestructive procedure. The device includes an integrated contrast agent delivery mechanism and a computerized depth scan system. The instrument uses a fiber bundle to relay the image plane of a slit-scan confocal microlaparoscope into tissue. The confocal laparoscope was used to image the ovaries of twenty-one patients in vivo using fluorescein sodium and acridine orange as the fluorescent contrast agents. The results indicate that the device is safe and functions as designed. A Monte Carlo model was developed to characterize the system performance in a scattering media representative of human tissues. The results indicate that a slit aperture has limited ability to image below the surface of tissue. In contrast, the results show that multi-pinhole apertures such as a Nipkow disk or a linear pinhole array can achieve nearly the same depth performance as a single pinhole aperture. The model was used to determine the optimal aperture spacing for the multi-pinhole apertures. The confocal microlaparoscope represents a new type of in vivo imaging device. With its ability to image cellular details in real time, it has the potential to aid in the early diagnosis of cancer. Initially, the device may be used to locate unusual regions for guided biopsies. In the long term, the device may be able to supplant traditional biopsies and allow the surgeon to identify early stage cancer in vivo.

Organic-inorganic interface-induced multi-fluorescence of MgO nanocrystal clusters and their applications in cellular imaging.

PubMed

Xie, Shuifen; Bao, Shixiong; Ouyang, Junjie; Zhou, Xi; Kuang, Qin; Xie, Zhaoxiong; Zheng, Lansun

2014-04-25

Surface functionalization of inorganic nanomaterials through chemical binding of organic ligands on the surface unsaturated atoms, forming unique organic-inorganic interfaces, is a powerful approach for creating special functions for inorganic nanomaterials. Herein, we report the synthesis of hierarchical MgO nanocrystal clusters (NCs) with an organic-inorganic interface induced multi-fluorescence and their application as new alternative labels for cellular imaging. The synthetic method was established by a dissolution and regrowth process with the assistance of carboxylic acid, in which the as-prepared MgO NCs were modified with carboxylic groups at the coordinatively unsaturated atoms of the surface. By introducing acetic acid to partially replace oleic acid in the reaction, the optical absorption of the produced MgO NCs was progressively engineered from the UV to the visible region. Importantly, with wider and continuous absorption profile, those MgO NCs presented bright and tunable multicolor emissions from blue-violet to green and yellow, with the highest absolute quantum yield up to (33±1) %. The overlap for the energy levels of the inorganic-organic interface and low-coordinated states stimulated a unique fluorescence resonance energy transfer phenomenon. Considering the potential application in cellular imaging, such multi-fluorescent MgO NCs were further encapsulated with a silica shell to improve the water solubility and stability. As expected, the as-formed MgO@SiO2 NCs possessed great biocompatibility and high performance in cellular imaging. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Faceted Discrete Growth and Phase Differentiation During the Directional Solidification of 20SiMnMo5 Steel

NASA Astrophysics Data System (ADS)

Ma, Xiaoping; Li, Dianzhong

2018-07-01

The microstructures, segregation and cooling curve were investigated in the directional solidification of 20SiMnMo5 steel. The typical characteristic of faceted growth is identified. The microstructures within the single cellular and within the single dendritic arm, together with the contradictive segregation distribution against the cooling curve, verify the discrete crystal growth in multi-scales. Not only the single cellular/dendritic arm but also the single martensite zone within the single cellular/dendritic arm is produced by the discrete growth. In the viewpoint of segregation, the basic domain following continuous growth has not been revealed. Along with the multi-scale faceted discrete growth, the phase differentiation happens for both the solid and liquid. The differentiated liquid phases appear and evolve with different sizes, positions, compositions and durations. The physical mechanism for the faceted discrete growth is qualitatively established based on the nucleation of new faceted steps induced by the composition gradient and temperature gradient.

Mapping the dynamics of force transduction at cell–cell junctions of epithelial clusters

PubMed Central

Ng, Mei Rosa; Besser, Achim; Brugge, Joan S; Danuser, Gaudenz

2014-01-01

Force transduction at cell-cell adhesions regulates tissue development, maintenance and adaptation. We developed computational and experimental approaches to quantify, with both sub-cellular and multi-cellular resolution, the dynamics of force transmission in cell clusters. Applying this technology to spontaneously-forming adherent epithelial cell clusters, we found that basal force fluctuations were coupled to E-cadherin localization at the level of individual cell-cell junctions. At the multi-cellular scale, cell-cell force exchange depended on the cell position within a cluster, and was adaptive to reconfigurations due to cell divisions or positional rearrangements. Importantly, force transmission through a cell required coordinated modulation of cell-matrix adhesion and actomyosin contractility in the cell and its neighbors. These data provide insights into mechanisms that could control mechanical stress homeostasis in dynamic epithelial tissues, and highlight our methods as a resource for the study of mechanotransduction in cell-cell adhesions. DOI: http://dx.doi.org/10.7554/eLife.03282.001 PMID:25479385

The Faceted Discrete Growth and Phase Differentiation During the Directional Solidification of 20SiMnMo5 Steel

NASA Astrophysics Data System (ADS)

Ma, Xiaoping; Li, Dianzhong

2018-03-01

The microstructures, segregation and cooling curve were investigated in the directional solidification of 20SiMnMo5 steel. The typical characteristic of faceted growth is identified. The microstructures within the single cellular and within the single dendritic arm, together with the contradictive segregation distribution against the cooling curve, verify the discrete crystal growth in multi-scales. Not only the single cellular/dendritic arm but also the single martensite zone within the single cellular/dendritic arm is produced by the discrete growth. In the viewpoint of segregation, the basic domain following continuous growth has not been revealed. Along with the multi-scale faceted discrete growth, the phase differentiation happens for both the solid and liquid. The differentiated liquid phases appear and evolve with different sizes, positions, compositions and durations. The physical mechanism for the faceted discrete growth is qualitatively established based on the nucleation of new faceted steps induced by the composition gradient and temperature gradient.

System and method for monitoring cellular activity

NASA Technical Reports Server (NTRS)

Bearman, Gregory H. (Inventor); Fraser, Scott E. (Inventor); Lansford, Russell D. (Inventor)

2002-01-01

A system and method for monitoring cellular activity in a cellular specimen. According to one embodiment, a plurality of excitable markers are applied to the specimen. A multi-photon laser microscope is provided to excite a region of the specimen and cause fluorescence to be radiated from the region. The radiating fluorescence is processed by a spectral analyzer to separate the fluorescence into respective wavelength bands. The respective bands of fluorescence are then collected by an array of detectors, with each detector receiving a corresponding one of the wavelength bands.

System and method for monitoring cellular activity

NASA Technical Reports Server (NTRS)

Bearman, Gregory H. (Inventor); Fraser, Scott E. (Inventor); Lansford, Russell D. (Inventor)

2004-01-01

A system and method for monitoring cellular activity in a cellular specimen. According to one embodiment, a plurality of excitable markers are applied to the specimen. A multi-photon laser microscope is provided to excite a region of the specimen and cause fluorescence to be radiated from the region. The radiating fluorescence is processed by a spectral analyzer to separate the fluorescence into respective wavelength bands. The respective bands of fluorescence are then collected by an array of detectors, with each detector receiving a corresponding one of the wavelength bands.

ParTIES: a toolbox for Paramecium interspersed DNA elimination studies.

PubMed

Denby Wilkes, Cyril; Arnaiz, Olivier; Sperling, Linda

2016-02-15

Developmental DNA elimination occurs in a wide variety of multicellular organisms, but ciliates are the only single-celled eukaryotes in which this phenomenon has been reported. Despite considerable interest in ciliates as models for DNA elimination, no standard methods for identification and characterization of the eliminated sequences are currently available. We present the Paramecium Toolbox for Interspersed DNA Elimination Studies (ParTIES), designed for Paramecium species, that (i) identifies eliminated sequences, (ii) measures their presence in a sequencing sample and (iii) detects rare elimination polymorphisms. ParTIES is multi-threaded Perl software available at https://github.com/oarnaiz/ParTIES. ParTIES is distributed under the GNU General Public Licence v3. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Developmental Stability Covaries with Genome-Wide and Single-Locus Heterozygosity in House Sparrows

PubMed Central

Vangestel, Carl; Mergeay, Joachim; Dawson, Deborah A.; Vandomme, Viki; Lens, Luc

2011-01-01

Fluctuating asymmetry (FA), a measure of developmental instability, has been hypothesized to increase with genetic stress. Despite numerous studies providing empirical evidence for associations between FA and genome-wide properties such as multi-locus heterozygosity, support for single-locus effects remains scant. Here we test if, and to what extent, FA co-varies with single- and multilocus markers of genetic diversity in house sparrow (Passer domesticus) populations along an urban gradient. In line with theoretical expectations, FA was inversely correlated with genetic diversity estimated at genome level. However, this relationship was largely driven by variation at a single key locus. Contrary to our expectations, relationships between FA and genetic diversity were not stronger in individuals from urban populations that experience higher nutritional stress. We conclude that loss of genetic diversity adversely affects developmental stability in P. domesticus, and more generally, that the molecular basis of developmental stability may involve complex interactions between local and genome-wide effects. Further study on the relative effects of single-locus and genome-wide effects on the developmental stability of populations with different genetic properties is therefore needed. PMID:21747940

14 CFR § 1274.905 - Rights in data.

Code of Federal Regulations, 2014 CFR

2014-01-01

... collaborative research, experimental, developmental, engineering, demonstration, or design activities are to be... under the agreement. If cost sharing is unequal or no extensive research, experimental, developmental, engineering, demonstration, or design activities are likely, a different set of provisions may be appropriate...

Fluidic origami with embedded pressure dependent multi-stability: a plant inspired innovation

PubMed Central

Li, Suyi; Wang, K. W.

2015-01-01

Inspired by the impulsive movements in plants, this research investigates the physics of a novel fluidic origami concept for its pressure-dependent multi-stability. In this innovation, fluid-filled tubular cells are synthesized by integrating different Miura-Ori sheets into a three-dimensional topological system, where the internal pressures are strategically controlled similar to the motor cells in plants. Fluidic origami incorporates two crucial physiological features observed in nature: one is distributed, pressurized cellular organization, and the other is embedded multi-stability. For a single fluidic origami cell, two stable folding configurations can coexist due to the nonlinear relationships among folding, crease material deformation and internal volume change. When multiple origami cells are integrated, additional multi-stability characteristics could occur via the interactions between pressurized cells. Changes in the fluid pressure can tailor the existence and shapes of these stable folding configurations. As a result, fluidic origami can switch between being mono-stable, bistable and multi-stable with pressure control, and provide a rapid ‘snap-through’ type of shape change based on the similar principles as in plants. The outcomes of this research could lead to the development of new adaptive materials or structures, and provide insights for future plant physiology studies at the cellular level. PMID:26400197

Fluidic origami with embedded pressure dependent multi-stability: a plant inspired innovation.

PubMed

Li, Suyi; Wang, K W

2015-10-06

Inspired by the impulsive movements in plants, this research investigates the physics of a novel fluidic origami concept for its pressure-dependent multi-stability. In this innovation, fluid-filled tubular cells are synthesized by integrating different Miura-Ori sheets into a three-dimensional topological system, where the internal pressures are strategically controlled similar to the motor cells in plants. Fluidic origami incorporates two crucial physiological features observed in nature: one is distributed, pressurized cellular organization, and the other is embedded multi-stability. For a single fluidic origami cell, two stable folding configurations can coexist due to the nonlinear relationships among folding, crease material deformation and internal volume change. When multiple origami cells are integrated, additional multi-stability characteristics could occur via the interactions between pressurized cells. Changes in the fluid pressure can tailor the existence and shapes of these stable folding configurations. As a result, fluidic origami can switch between being mono-stable, bistable and multi-stable with pressure control, and provide a rapid 'snap-through' type of shape change based on the similar principles as in plants. The outcomes of this research could lead to the development of new adaptive materials or structures, and provide insights for future plant physiology studies at the cellular level. © 2015 The Author(s).

A Comparison of Developmental Sentence Scores from Head Start Children Collected in Four Conditions

ERIC Educational Resources Information Center

Longhurst, Thomas M.; File, Judy J.

1977-01-01

In a comparison of expressive language in different settings, 20 economically disadvantaged students in a Head Start program were divided into four groups: single-object picture, toy, multi-object picture, and adult-child conversation. (CL)

Realizing the Potential of Adolescence to Prevent Transgenerational Conditioning of Noncommunicable Disease Risk: Multi-Sectoral Design Frameworks

PubMed Central

Bay, Jacquie L.; Morton, Susan M.; Vickers, Mark H.

2016-01-01

Evidence from the field of Developmental Origins of Health and Disease (DOHaD) demonstrates that early life environmental exposures impact later-life risk of non-communicable diseases (NCDs). This has revealed the transgenerational nature of NCD risk, thus demonstrating that interventions to improve environmental exposures during early life offer important potential for primary prevention of DOHaD-related NCDs. Based on this evidence, the prospect of multi-sectoral approaches to enable primary NCD risk reduction has been highlighted in major international reports. It is agreed that pregnancy, lactation and early childhood offer significant intervention opportunities. However, the importance of interventions that establish positive behaviors impacting nutritional and non-nutritional environmental exposures in the pre-conceptual period in both males and females, thus capturing the full potential of DOHaD, must not be overlooked. Adolescence, a period where life-long health-related behaviors are established, is therefore an important life-stage for DOHaD-informed intervention. DOHaD evidence underpinning this potential is well documented. However, there is a gap in the literature with respect to combined application of theoretical evidence from science, education and public health to inform intervention design. This paper addresses this gap, presenting a review of evidence informing theoretical frameworks for adolescent DOHaD interventions that is accessible collectively to all relevant sectors. PMID:27417627

[Developmental status and prospect of musical electroacupuncture].

PubMed

Wang, Fan; Xu, Chun-Lan; Dong, Gui-Rong; Dong, Hong-Sheng

2014-12-01

Through searching domestic and foreign medical journals in CNKI, Wanfang database, VIP database and Pubmed database from January of 2003 to November of 2013, 39 articles regarding musical electroacupuncture (MEA) were analyzed. The result showed that MEA was clinically used to treat neurological and psychotic disorders; because it was combined with musical therapy and overcame the acupuncture tolerability, and MEA was superior to traditional electroacupuncture. However, problems such as low research efficiency and the mechanism of MEA superiority and the musical specificity not being revealed by research design still exist. In future, large-sample multi-center RCT researches should be performed to clarify MEA clinical efficacy. With modern science and technology and optimized study design, guided by five-element theory of TCM, researches on different musical elements and characteristics of musical pulse current as well as MEA's correlation with meridians and organs should be studied, so as to make a further exploration on MEA mechanisms and broaden the range of its clinical application.

Results of solar electric thrust vector control system design, development and tests

NASA Technical Reports Server (NTRS)

Fleischer, G. E.

1973-01-01

Efforts to develop and test a thrust vector control system TVCS for a solar-energy-powered ion engine array are described. The results of solar electric propulsion system technology (SEPST) III real-time tests of present versions of TVCS hardware in combination with computer-simulated attitude dynamics of a solar electric multi-mission spacecraft (SEMMS) Phase A-type spacecraft configuration are summarized. Work on an improved solar electric TVCS, based on the use of a state estimator, is described. SEPST III tests of TVCS hardware have generally proved successful and dynamic response of the system is close to predictions. It appears that, if TVCS electronic hardware can be effectively replaced by control computer software, a significant advantage in control capability and flexibility can be gained in future developmental testing, with practical implications for flight systems as well. Finally, it is concluded from computer simulations that TVCS stabilization using rate estimation promises a substantial performance improvement over the present design.

NeuroLines: A Subway Map Metaphor for Visualizing Nanoscale Neuronal Connectivity.

PubMed

Al-Awami, Ali K; Beyer, Johanna; Strobelt, Hendrik; Kasthuri, Narayanan; Lichtman, Jeff W; Pfister, Hanspeter; Hadwiger, Markus

2014-12-01

We present NeuroLines, a novel visualization technique designed for scalable detailed analysis of neuronal connectivity at the nanoscale level. The topology of 3D brain tissue data is abstracted into a multi-scale, relative distance-preserving subway map visualization that allows domain scientists to conduct an interactive analysis of neurons and their connectivity. Nanoscale connectomics aims at reverse-engineering the wiring of the brain. Reconstructing and analyzing the detailed connectivity of neurons and neurites (axons, dendrites) will be crucial for understanding the brain and its development and diseases. However, the enormous scale and complexity of nanoscale neuronal connectivity pose big challenges to existing visualization techniques in terms of scalability. NeuroLines offers a scalable visualization framework that can interactively render thousands of neurites, and that supports the detailed analysis of neuronal structures and their connectivity. We describe and analyze the design of NeuroLines based on two real-world use-cases of our collaborators in developmental neuroscience, and investigate its scalability to large-scale neuronal connectivity data.

Computation Modeling of Limb-bud Dysmorphogenesis: Predicting Cellular Dynamics and Key Events in Developmental Toxicity with a Multicellular Systems Model (FutureToxII)

EPA Science Inventory

Congenital limb malformations are among the most frequent malformation occurs in humans, with a frequency of about 1 in 500 to 1 in 1000 human live births. ToxCast is profiling the bioactivity of thousands of chemicals based on high-throughput (HTS) and computational methods that...

Recapitulation of developmental mechanisms to revascularize the ischemic heart

PubMed Central

Dubé, Karina N.; Thomas, Tonia M.; Munshaw, Sonali; Rohling, Mala; Riley, Paul R.

2017-01-01

Restoring blood flow after myocardial infarction (MI) is essential for survival of existing and newly regenerated tissue. Endogenous vascular repair processes are deployed following injury but are poorly understood. We sought to determine whether developmental mechanisms of coronary vessel formation are intrinsically reactivated in the adult mouse after MI. Using pulse-chase genetic lineage tracing, we establish that de novo vessel formation constitutes a substantial component of the neovascular response, with apparent cellular contributions from the endocardium and coronary sinus. The adult heart reverts to its former hypertrabeculated state and repeats the process of compaction, which may facilitate endocardium-derived neovascularization. The capacity for angiogenic sprouting of the coronary sinus vein, the adult derivative of the sinus venosus, may also reflect its embryonic origin. The quiescent epicardium is reactivated and, while direct cellular contribution to new vessels is minimal, it supports the directional expansion of the neovessel network toward the infarcted myocardium. Thymosin β4, a peptide with roles in vascular development, was required for endocardial compaction, epicardial vessel expansion, and smooth muscle cell recruitment. Insight into pathways that regulate endogenous vascular repair, drawing on comparisons with development, may reveal novel targets for therapeutically enhancing neovascularization. PMID:29202457

Serotonin homeostasis and serotonin receptors as actors of cortical construction: special attention to the 5-HT3A and 5-HT6 receptor subtypes

PubMed Central

Vitalis, Tania; Ansorge, Mark S.; Dayer, Alexandre G.

2013-01-01

Cortical circuits control higher-order cognitive processes and their function is highly dependent on their structure that emerges during development. The construction of cortical circuits involves the coordinated interplay between different types of cellular processes such as proliferation, migration, and differentiation of neural and glial cell subtypes. Among the multiple factors that regulate the assembly of cortical circuits, 5-HT is an important developmental signal that impacts on a broad diversity of cellular processes. 5-HT is detected at the onset of embryonic telencephalic formation and a variety of serotonergic receptors are dynamically expressed in the embryonic developing cortex in a region and cell-type specific manner. Among these receptors, the ionotropic 5-HT3A receptor and the metabotropic 5-HT6 receptor have recently been identified as novel serotonergic targets regulating different aspects of cortical construction including neuronal migration and dendritic differentiation. In this review, we focus on the developmental impact of serotonergic systems on the construction of cortical circuits and discuss their potential role in programming risk for human psychiatric disorders. PMID:23801939

Embedding Language Support in Developmental Mathematics Lessons: Exploring the Value of Design as Professional Development for Community College Mathematics Instructors

ERIC Educational Resources Information Center

Gomez, Kimberley; Gomez, Louis M.; Rodela, Katherine C.; Horton, Emily S.; Cunningham, Jahneille; Ambrocio, Rocio

2015-01-01

Three community college faculty members used improvement science techniques to design, develop, and refine contextualized developmental mathematics lessons, where language and literacy pedagogy and related supports figured prominently in these instructional materials. This article reports on the role that their design experiences played in…

Sampling Development

ERIC Educational Resources Information Center

Adolph, Karen E.; Robinson, Scott R.

2011-01-01

Research in developmental psychology requires sampling at different time points. Accurate depictions of developmental change provide a foundation for further empirical studies and theories about developmental mechanisms. However, overreliance on widely spaced sampling intervals in cross-sectional and longitudinal designs threatens the validity of…

Design and Construction of a Multi-wavelength, Micromirror Total Internal Reflectance Fluorescence Microscope

PubMed Central

Larson, Joshua; Kirk, Matt; Drier, Eric A.; O’Brien, William; MacKay, James F.; Friedman, Larry; Hoskins, Aaron

2015-01-01

Colocalization Single Molecule Spectroscopy (CoSMoS) has proven to be a useful method for studying the composition, kinetics, and mechanisms of complex cellular machines. Key to the technique is the ability to simultaneously monitor multiple proteins and/or nucleic acids as they interact with one another. Here we describe a protocol for constructing a CoSMoS micromirror Total Internal Reflection Fluorescence Microscope (mmTIRFM). Design and construction of a scientific microscope often requires a number of custom components and a significant time commitment. In our protocol, we have streamlined this process by implementation of a commercially available microscopy platform designed to accommodate the optical components necessary for a mmTIRFM. The mmTIRF system eliminates the need for machining custom parts by the end-user and facilitates optical alignment. Depending on the experience-level of the microscope builder, these time-savings and the following protocol can enable mmTIRF construction to be completed within two months. PMID:25188633

A Mobile Robot for Locomotion Through a 3D Periodic Lattice Environment

NASA Technical Reports Server (NTRS)

Jenett, Benjamin; Cellucci, Daniel; Cheung, Kenneth

2017-01-01

This paper describes a novel class of robots specifically adapted to climb periodic lattices, which we call 'Relative Robots'. These robots use the regularity of the structure to simplify the path planning, align with minimal feedback, and reduce the number of degrees of freedom (DOF) required to locomote. They can perform vital inspection and repair tasks within the structure that larger truss construction robots could not perform without modifying the structure. We detail a specific type of relative robot designed to traverse a cuboctahedral (CubOct) cellular solids lattice, show how the symmetries of the lattice simplify the design, and test these design methodologies with a CubOct relative robot that traverses a 76.2 mm (3 in.) pitch lattice, MOJO (Multi-Objective JOurneying robot). We perform three locomotion tasks with MOJO: vertical climbing, horizontal climbing, and turning, and find that, due to changes in the orientation of the robot relative to the gravity vector, the success rate of vertical and horizontal climbing is significantly different.

New concept: cellular senescence in pathophysiology of cholangiocarcinoma.

PubMed

Sasaki, Motoko; Nakanuma, Yasuni

2016-01-01

Cholangiocarcinoma, a malignant tumor arising in the hepatobiliary system, presents with poor prognosis because of difficulty in its early detection/diagnosis. Recent progress revealed that cellular senescence may be involved in the pathophysiology of cholangiocarcinoma. Cellular senescence is defined as permanent growth arrest caused by several cellular injuries, such as oncogenic mutations and oxidative stress. "Oncogene-induced" and/or stress-induced senescence may occur in the process of multi-step cholangiocarcinogenesis, and overexpression of a polycomb group protein EZH2 may play a role in the escape from, and/or bypassing of, senescence. Furthermore, senescent cells may play important roles in tumor development and progression via the production of senescence-associated secretory phenotypes. Cellular senescence may be a new target for the prevention, early diagnosis, and therapy of cholangiocarcinoma in the near future.

Developmental Regulation of Nucleolus Size during Drosophila Eye Differentiation

PubMed Central

Baker, Nicholas E.

2013-01-01

When cell cycle withdrawal accompanies terminal differentiation, biosynthesis and cellular growth are likely to change also. In this study, nucleolus size was monitored during cell fate specification in the Drosophila eye imaginal disc using fibrillarin antibody labeling. Nucleolus size is an indicator of ribosome biogenesis and can correlate with cellular growth rate. Nucleolar size was reduced significantly during cell fate specification and differentiation, predominantly as eye disc cells entered a cell cycle arrest that preceded cell fate specification. This reduction in nucleolus size required Dpp and Hh signaling. A transient enlargement of the nucleolus accompanied cell division in the Second Mitotic Wave. Nucleoli continued to diminish in postmitotic cells following fate specification. These results suggest that cellular growth is regulated early in the transition from proliferating progenitor cells to terminal cell fate specification, contemporary with regulation of the cell cycle, and requiring the same extracellular signals. PMID:23472166

Endocytosis and Endosomal Trafficking in Plants.

PubMed

Paez Valencia, Julio; Goodman, Kaija; Otegui, Marisa S

2016-04-29

Endocytosis and endosomal trafficking are essential processes in cells that control the dynamics and turnover of plasma membrane proteins, such as receptors, transporters, and cell wall biosynthetic enzymes. Plasma membrane proteins (cargo) are internalized by endocytosis through clathrin-dependent or clathrin-independent mechanism and delivered to early endosomes. From the endosomes, cargo proteins are recycled back to the plasma membrane via different pathways, which rely on small GTPases and the retromer complex. Proteins that are targeted for degradation through ubiquitination are sorted into endosomal vesicles by the ESCRT (endosomal sorting complex required for transport) machinery for degradation in the vacuole. Endocytic and endosomal trafficking regulates many cellular, developmental, and physiological processes, including cellular polarization, hormone transport, metal ion homeostasis, cytokinesis, pathogen responses, and development. In this review, we discuss the mechanisms that mediate the recognition and sorting of endocytic and endosomal cargos, the vesiculation processes that mediate their trafficking, and their connection to cellular and physiological responses in plants.

Oxidative Stress, Bone Marrow Failure, and Genome Instability in Hematopoietic Stem Cells

PubMed Central

Richardson, Christine; Yan, Shan; Vestal, C. Greer

2015-01-01

Reactive oxygen species (ROS) can be generated by defective endogenous reduction of oxygen by cellular enzymes or in the mitochondrial respiratory pathway, as well as by exogenous exposure to UV or environmental damaging agents. Regulation of intracellular ROS levels is critical since increases above normal concentrations lead to oxidative stress and DNA damage. A growing body of evidence indicates that the inability to regulate high levels of ROS leading to alteration of cellular homeostasis or defective repair of ROS-induced damage lies at the root of diseases characterized by both neurodegeneration and bone marrow failure as well as cancer. That these diseases may be reflective of the dynamic ability of cells to respond to ROS through developmental stages and aging lies in the similarities between phenotypes at the cellular level. This review summarizes work linking the ability to regulate intracellular ROS to the hematopoietic stem cell phenotype, aging, and disease. PMID:25622253

Developmental regulation of nucleolus size during Drosophila eye differentiation.

PubMed

Baker, Nicholas E

2013-01-01

When cell cycle withdrawal accompanies terminal differentiation, biosynthesis and cellular growth are likely to change also. In this study, nucleolus size was monitored during cell fate specification in the Drosophila eye imaginal disc using fibrillarin antibody labeling. Nucleolus size is an indicator of ribosome biogenesis and can correlate with cellular growth rate. Nucleolar size was reduced significantly during cell fate specification and differentiation, predominantly as eye disc cells entered a cell cycle arrest that preceded cell fate specification. This reduction in nucleolus size required Dpp and Hh signaling. A transient enlargement of the nucleolus accompanied cell division in the Second Mitotic Wave. Nucleoli continued to diminish in postmitotic cells following fate specification. These results suggest that cellular growth is regulated early in the transition from proliferating progenitor cells to terminal cell fate specification, contemporary with regulation of the cell cycle, and requiring the same extracellular signals.

Postnatal Exocrine Pancreas Growth by Cellular Hypertrophy Correlates with a Shorter Lifespan in Mammals.

PubMed

Anzi, Shira; Stolovich-Rain, Miri; Klochendler, Agnes; Fridlich, Ori; Helman, Aharon; Paz-Sonnenfeld, Avital; Avni-Magen, Nili; Kaufman, Elizabeth; Ginzberg, Miriam B; Snider, Daniel; Ray, Saikat; Brecht, Michael; Holmes, Melissa M; Meir, Karen; Avivi, Aaron; Shams, Imad; Berkowitz, Asaf; Shapiro, A M James; Glaser, Benjamin; Ben-Sasson, Shmuel; Kafri, Ran; Dor, Yuval

2018-06-18

Developmental processes in different mammals are thought to share fundamental cellular mechanisms. We report a dramatic increase in cell size during postnatal pancreas development in rodents, accounting for much of the increase in organ size after birth. Hypertrophy of pancreatic acinar cells involves both higher ploidy and increased biosynthesis per genome copy; is maximal adjacent to islets, suggesting endocrine to exocrine communication; and is partly driven by weaning-related processes. In contrast to the situation in rodents, pancreas cell size in humans remains stable postnatally, indicating organ growth by pure hyperplasia. Pancreatic acinar cell volume varies 9-fold among 24 mammalian species analyzed, and shows a striking inverse correlation with organismal lifespan. We hypothesize that cellular hypertrophy is a strategy for rapid postnatal tissue growth, entailing life-long detrimental effects. Copyright © 2018 Elsevier Inc. All rights reserved.

Understanding retirement: the promise of life-span developmental frameworks.

PubMed

Löckenhoff, Corinna E

2012-09-01

The impending retirement of large population cohorts creates a pressing need for practical interventions to optimize outcomes at the individual and societal level. This necessitates comprehensive theoretical models that acknowledge the multi-layered nature of the retirement process and shed light on the dynamic mechanisms that drive longitudinal patterns of adjustment. The present commentary highlights ways in which contemporary life-span developmental frameworks can inform retirement research, drawing on the specific examples of Bronfenbrenner's Ecological Model, Baltes and Baltes Selective Optimization with Compensation Framework, Schulz and Heckhausen's Motivational Theory of Life-Span Development, and Carstensen's Socioemotional Selectivity Theory. Ultimately, a life-span developmental perspective on retirement offers not only new interpretations of known phenomena but may also help to identify novel directions for future research as well as promising pathways for interventions.

Mapping human pluripotent stem cell differentiation pathways using high throughput single-cell RNA-sequencing.

PubMed

Han, Xiaoping; Chen, Haide; Huang, Daosheng; Chen, Huidong; Fei, Lijiang; Cheng, Chen; Huang, He; Yuan, Guo-Cheng; Guo, Guoji

2018-04-05

Human pluripotent stem cells (hPSCs) provide powerful models for studying cellular differentiations and unlimited sources of cells for regenerative medicine. However, a comprehensive single-cell level differentiation roadmap for hPSCs has not been achieved. We use high throughput single-cell RNA-sequencing (scRNA-seq), based on optimized microfluidic circuits, to profile early differentiation lineages in the human embryoid body system. We present a cellular-state landscape for hPSC early differentiation that covers multiple cellular lineages, including neural, muscle, endothelial, stromal, liver, and epithelial cells. Through pseudotime analysis, we construct the developmental trajectories of these progenitor cells and reveal the gene expression dynamics in the process of cell differentiation. We further reprogram primed H9 cells into naïve-like H9 cells to study the cellular-state transition process. We find that genes related to hemogenic endothelium development are enriched in naïve-like H9. Functionally, naïve-like H9 show higher potency for differentiation into hematopoietic lineages than primed cells. Our single-cell analysis reveals the cellular-state landscape of hPSC early differentiation, offering new insights that can be harnessed for optimization of differentiation protocols.

The Role of H1 Linker Histone Subtypes in Preserving the Fidelity of Elaboration of Mesendodermal and Neuroectodermal Lineages during Embryonic Development

PubMed Central

Nguyen, Giang D.; Gokhan, Solen; Molero, Aldrin E.; Yang, Seung-Min; Kim, Byung-Ju; Skoultchi, Arthur I.; Mehler, Mark F.

2014-01-01

H1 linker histone proteins are essential for the structural and functional integrity of chromatin and for the fidelity of additional epigenetic modifications. Deletion of H1c, H1d and H1e in mice leads to embryonic lethality by mid-gestation with a broad spectrum of developmental alterations. To elucidate the cellular and molecular mechanisms underlying H1 linker histone developmental functions, we analyzed embryonic stem cells (ESCs) depleted of H1c, H1d and H1e subtypes (H1-KO ESCs) by utilizing established ESC differentiation paradigms. Our study revealed that although H1-KO ESCs continued to express core pluripotency genes and the embryonic stem cell markers, alkaline phosphatase and SSEA1, they exhibited enhanced cell death during embryoid body formation and during specification of mesendoderm and neuroectoderm. In addition, we demonstrated deregulation in the developmental programs of cardiomyocyte, hepatic and pancreatic lineage elaboration. Moreover, ectopic neurogenesis and cardiomyogenesis occurred during endoderm-derived pancreatic but not hepatic differentiation. Furthermore, neural differentiation paradigms revealed selective impairments in the specification and maturation of glutamatergic and dopaminergic neurons with accelerated maturation of glial lineages. These impairments were associated with deregulation in the expression profiles of pro-neural genes in dorsal and ventral forebrain-derived neural stem cell species. Taken together, these experimental observations suggest that H1 linker histone proteins are critical for the specification, maturation and fidelity of organ-specific cellular lineages derived from the three cardinal germ layers. PMID:24802750

Analysis of global gene expression profiles to identify differentially expressed genes critical for embryo development in Brassica rapa.

PubMed

Zhang, Yu; Peng, Lifang; Wu, Ya; Shen, Yanyue; Wu, Xiaoming; Wang, Jianbo

2014-11-01

Embryo development represents a crucial developmental period in the life cycle of flowering plants. To gain insights into the genetic programs that control embryo development in Brassica rapa L., RNA sequencing technology was used to perform transcriptome profiling analysis of B. rapa developing embryos. The results generated 42,906,229 sequence reads aligned with 32,941 genes. In total, 27,760, 28,871, 28,384, and 25,653 genes were identified from embryos at globular, heart, early cotyledon, and mature developmental stages, respectively, and analysis between stages revealed a subset of stage-specific genes. We next investigated 9,884 differentially expressed genes with more than fivefold changes in expression and false discovery rate ≤ 0.001 from three adjacent-stage comparisons; 1,514, 3,831, and 6,633 genes were detected between globular and heart stage embryo libraries, heart stage and early cotyledon stage, and early cotyledon and mature stage, respectively. Large numbers of genes related to cellular process, metabolism process, response to stimulus, and biological process were expressed during the early and middle stages of embryo development. Fatty acid biosynthesis, biosynthesis of secondary metabolites, and photosynthesis-related genes were expressed predominantly in embryos at the middle stage. Genes for lipid metabolism and storage proteins were highly expressed in the middle and late stages of embryo development. We also identified 911 transcription factor genes that show differential expression across embryo developmental stages. These results increase our understanding of the complex molecular and cellular events during embryo development in B. rapa and provide a foundation for future studies on other oilseed crops.

Holism and life manifestations: molecular and space-time biology.

PubMed

Krecek, J

2010-01-01

Appeals of philosophers to look for new concepts in sciences are being met with a weak response. Limited attention is paid to the relation between synthetic and analytic approach in solving problems of biology. An attempt is presented to open a discussion on a possible role of holism. The term "life manifestations" is used in accordance with phenomenology. Multicellular creatures maintain milieu intérieur to keep an aqueous milieu intracellulair in order to transform the energy of nutrients into the form utilizable for driving cellular life manifestations. Milieu intérieur enables to integrate this kind of manifestations into life manifestations of the whole multicellular creatures. The integration depends on a uniqueness and uniformity of the genome of cells, on their mutual recognition and adherence. The processes of ontogenetic development represent the natural mode of integration of cellular life manifestations. Functional systems of multicellular creatures are being established by organization of integrable cells using a wide range of developmental processes. Starting from the zygote division the new being displays all properties of a whole creature, although its life manifestations vary. Therefore, the whole organism is not only more than its parts, as supposed by holism, but also more than developmental stages of its life manifestations. Implicitly, the units of whole multicellular creature are rather molecular and developmental events than the cells per se. Holism, taking in mind the existence of molecular and space-time biology, could become a guide in looking for a new mode of the combination of analytical and synthetic reasoning in biology.

Multi-scale continuum modeling of biological processes: from molecular electro-diffusion to sub-cellular signaling transduction

NASA Astrophysics Data System (ADS)

Cheng, Y.; Kekenes-Huskey, P.; Hake, J. E.; Holst, M. J.; McCammon, J. A.; Michailova, A. P.

2012-01-01

This paper presents a brief review of multi-scale modeling at the molecular to cellular scale, with new results for heart muscle cells. A finite element-based simulation package (SMOL) was used to investigate the signaling transduction at molecular and sub-cellular scales (http://mccammon.ucsd.edu/smol/, http://FETK.org) by numerical solution of the time-dependent Smoluchowski equations and a reaction-diffusion system. At the molecular scale, SMOL has yielded experimentally validated estimates of the diffusion-limited association rates for the binding of acetylcholine to mouse acetylcholinesterase using crystallographic structural data. The predicted rate constants exhibit increasingly delayed steady-state times, with increasing ionic strength, and demonstrate the role of an enzyme's electrostatic potential in influencing ligand binding. At the sub-cellular scale, an extension of SMOL solves a nonlinear, reaction-diffusion system describing Ca2+ ligand buffering and diffusion in experimentally derived rodent ventricular myocyte geometries. Results reveal the important role of mobile and stationary Ca2+ buffers, including Ca2+ indicator dye. We found that alterations in Ca2+-binding and dissociation rates of troponin C (TnC) and total TnC concentration modulate sub-cellular Ca2+ signals. The model predicts that reduced off-rate in the whole troponin complex (TnC, TnI, TnT) versus reconstructed thin filaments (Tn, Tm, actin) alters cytosolic Ca2+ dynamics under control conditions or in disease-linked TnC mutations. The ultimate goal of these studies is to develop scalable methods and theories for the integration of molecular-scale information into simulations of cellular-scale systems.

The Crabapple Experience: Insights from Program Evaluations.

ERIC Educational Resources Information Center

Elmore, Randy; Wisenbaker, Joe

2000-01-01

An evaluation of a Georgia middle school's multi-age grouping program revealed significant progress regarding student self-esteem, achievement, community building, and teacher collaboration. The Crabapple experience illustrates how one model of student-centered, developmentally appropriate, and integrated learning can benefit middle-level…

47 CFR 2.805 - Operation of radio frequency devices prior to equipment authorization.

Code of Federal Regulations, 2014 CFR

2014-10-01

... of performance and determination of customer acceptability, during developmental, design, or pre... performance and determination of customer acceptability, during developmental, design, or pre-production... authority of an experimental radio service authorization issued under part 5 of this chapter. (c) Operation...

Mutations in PIGY: expanding the phenotype of inherited glycosylphosphatidylinositol deficiencies

PubMed Central

Ilkovski, Biljana; Pagnamenta, Alistair T.; O'Grady, Gina L.; Kinoshita, Taroh; Howard, Malcolm F.; Lek, Monkol; Thomas, Brett; Turner, Anne; Christodoulou, John; Sillence, David; Knight, Samantha J.L.; Popitsch, Niko; Keays, David A.; Anzilotti, Consuelo; Goriely, Anne; Waddell, Leigh B.; Brilot, Fabienne; North, Kathryn N.; Kanzawa, Noriyuki; Macarthur, Daniel G.; Taylor, Jenny C.; Kini, Usha; Murakami, Yoshiko; Clarke, Nigel F.

2015-01-01

Glycosylphosphatidylinositol (GPI)-anchored proteins are ubiquitously expressed in the human body and are important for various functions at the cell surface. Mutations in many GPI biosynthesis genes have been described to date in patients with multi-system disease and together these constitute a subtype of congenital disorders of glycosylation. We used whole exome sequencing in two families to investigate the genetic basis of disease and used RNA and cellular studies to investigate the functional consequences of sequence variants in the PIGY gene. Two families with different phenotypes had homozygous recessive sequence variants in the GPI biosynthesis gene PIGY. Two sisters with c.137T>C (p.Leu46Pro) PIGY variants had multi-system disease including dysmorphism, seizures, severe developmental delay, cataracts and early death. There were significantly reduced levels of GPI-anchored proteins (CD55 and CD59) on the surface of patient-derived skin fibroblasts (∼20–50% compared with controls). In a second, consanguineous family, two siblings had moderate development delay and microcephaly. A homozygous PIGY promoter variant (c.-540G>A) was detected within a 7.7 Mb region of autozygosity. This variant was predicted to disrupt a SP1 consensus binding site and was shown to be associated with reduced gene expression. Mutations in PIGY can occur in coding and non-coding regions of the gene and cause variable phenotypes. This article contributes to understanding of the range of disease phenotypes and disease genes associated with deficiencies of the GPI-anchor biosynthesis pathway and also serves to highlight the potential importance of analysing variants detected in 5′-UTR regions despite their typically low coverage in exome data. PMID:26293662

Mutations in PIGY: expanding the phenotype of inherited glycosylphosphatidylinositol deficiencies.

PubMed

Ilkovski, Biljana; Pagnamenta, Alistair T; O'Grady, Gina L; Kinoshita, Taroh; Howard, Malcolm F; Lek, Monkol; Thomas, Brett; Turner, Anne; Christodoulou, John; Sillence, David; Knight, Samantha J L; Popitsch, Niko; Keays, David A; Anzilotti, Consuelo; Goriely, Anne; Waddell, Leigh B; Brilot, Fabienne; North, Kathryn N; Kanzawa, Noriyuki; Macarthur, Daniel G; Taylor, Jenny C; Kini, Usha; Murakami, Yoshiko; Clarke, Nigel F

2015-11-01

Glycosylphosphatidylinositol (GPI)-anchored proteins are ubiquitously expressed in the human body and are important for various functions at the cell surface. Mutations in many GPI biosynthesis genes have been described to date in patients with multi-system disease and together these constitute a subtype of congenital disorders of glycosylation. We used whole exome sequencing in two families to investigate the genetic basis of disease and used RNA and cellular studies to investigate the functional consequences of sequence variants in the PIGY gene. Two families with different phenotypes had homozygous recessive sequence variants in the GPI biosynthesis gene PIGY. Two sisters with c.137T>C (p.Leu46Pro) PIGY variants had multi-system disease including dysmorphism, seizures, severe developmental delay, cataracts and early death. There were significantly reduced levels of GPI-anchored proteins (CD55 and CD59) on the surface of patient-derived skin fibroblasts (∼20-50% compared with controls). In a second, consanguineous family, two siblings had moderate development delay and microcephaly. A homozygous PIGY promoter variant (c.-540G>A) was detected within a 7.7 Mb region of autozygosity. This variant was predicted to disrupt a SP1 consensus binding site and was shown to be associated with reduced gene expression. Mutations in PIGY can occur in coding and non-coding regions of the gene and cause variable phenotypes. This article contributes to understanding of the range of disease phenotypes and disease genes associated with deficiencies of the GPI-anchor biosynthesis pathway and also serves to highlight the potential importance of analysing variants detected in 5'-UTR regions despite their typically low coverage in exome data. © The Author 2015. Published by Oxford University Press.

Location and cellular stages of NK cell development

PubMed Central

Yu, Jianhua; Freud, Aharon G.; Caligiuri, Michael A

2013-01-01

The identification of distinct tissue-specific natural killer (NK) cell populations that apparently mature from local precursor populations has brought new insight into the diversity and developmental regulation of this important lymphoid subset. NK cells provide a necessary link between the early (innate) and late (adaptive) immune responses to infection. Gaining a better understanding of the processes that govern NK cell development should allow us to better harness NK cell functions in multiple clinical settings as well as to gain further insight into how these cells undergo malignant transformation. In this review, we summarize recent advances in understanding sites and cellular stages of NK cell development in humans and mice. PMID:24055329

Cellular and molecular mechanisms coordinating pancreas development.

PubMed

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

2017-08-15

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

The developmental origin of brain tumours: a cellular and molecular framework.

PubMed

Azzarelli, Roberta; Simons, Benjamin D; Philpott, Anna

2018-05-14

The development of the nervous system relies on the coordinated regulation of stem cell self-renewal and differentiation. The discovery that brain tumours contain a subpopulation of cells with stem/progenitor characteristics that are capable of sustaining tumour growth has emphasized the importance of understanding the cellular dynamics and the molecular pathways regulating neural stem cell behaviour. By focusing on recent work on glioma and medulloblastoma, we review how lineage tracing contributed to dissecting the embryonic origin of brain tumours and how lineage-specific mechanisms that regulate stem cell behaviour in the embryo may be subverted in cancer to achieve uncontrolled proliferation and suppression of differentiation. © 2018. Published by The Company of Biologists Ltd.

Large Cellular Inclusions Accumulate in Arabidopsis Roots Exposed to Low-Sulfur Conditions1[OPEN

PubMed Central

Popov, Vladimir A.; Mathur, Jaideep; Benfey, Philip N.

2015-01-01

Sulfur is vital for primary and secondary metabolism in plant roots. To understand the molecular and morphogenetic changes associated with loss of this key macronutrient, we grew Arabidopsis (Arabidopsis thaliana) seedlings in low-sulfur conditions. These conditions induced a cascade of cellular events that converged to produce a profound intracellular phenotype defined by large cytoplasmic inclusions. The inclusions, termed low-sulfur Pox, show cell type- and developmental zone-specific localization. Transcriptome analysis suggested that low sulfur causes dysfunction of the glutathione/ascorbate cycle, which reduces flavonoids. Genetic and biochemical evidence indicated that low-sulfur Pox are the result of peroxidase-catalyzed oxidation of quercetin in roots grown under sulfur-depleted conditions. PMID:26099270

The sweet spot: FDG and other 2-carbon glucose analogs for multi-modal metabolic imaging of tumor metabolism

PubMed Central

Cox, Benjamin L; Mackie, Thomas R; Eliceiri, Kevin W

2015-01-01

Multi-modal imaging approaches of tumor metabolism that provide improved specificity, physiological relevance and spatial resolution would improve diagnosing of tumors and evaluation of tumor progression. Currently, the molecular probe FDG, glucose fluorinated with 18F at the 2-carbon, is the primary metabolic approach for clinical diagnostics with PET imaging. However, PET lacks the resolution necessary to yield intratumoral distributions of deoxyglucose, on the cellular level. Multi-modal imaging could elucidate this problem, but requires the development of new glucose analogs that are better suited for other imaging modalities. Several such analogs have been created and are reviewed here. Also reviewed are several multi-modal imaging studies that have been performed that attempt to shed light on the cellular distribution of glucose analogs within tumors. Some of these studies are performed in vitro, while others are performed in vivo, in an animal model. The results from these studies introduce a visualization gap between the in vitro and in vivo studies that, if solved, could enable the early detection of tumors, the high resolution monitoring of tumors during treatment, and the greater accuracy in assessment of different imaging agents. PMID:25625022

Evaluating the Effectiveness of Developmental Mathematics by Embedding a Randomized Experiment within a Regression Discontinuity Design

ERIC Educational Resources Information Center

Moss, Brian G.; Yeaton, William H.; Lloyd, Jane E.

2014-01-01

Using a novel design approach, a randomized experiment (RE) was embedded within a regression discontinuity (RD) design (R-RE-D) to evaluate the impact of developmental mathematics at a large midwestern college ("n" = 2,122). Within a region of uncertainty near the cut-score, estimates of benefit from a prospective RE were closely…

Fused oblique incidence reflectometry and confocal fluorescence microscopy

NASA Astrophysics Data System (ADS)

Risi, Matthew D.; Rouse, Andrew R.; Gmitro, Arthur F.

2011-03-01

Confocal microendoscopy provides real-time high resolution cellular level images via a minimally invasive procedure, but relies on exogenous fluorophores, has a relatively limited penetration depth (100 μm) and field of view (700 μm), and produces a high rate of detailed information to the user. A new catheter based multi-modal system has been designed that combines confocal imaging and oblique incidence reflectometry (OIR), which is a non-invasive method capable of rapidly extracting tissue absorption, μa, and reduced scattering, μ's, spectra from tissue. The system builds on previous developments of a custom slit-scan multi-spectral confocal microendoscope and is designed to rapidly switch between diffuse spectroscopy and confocal fluorescence imaging modes of operation. An experimental proof-of-principle catheter has been developed that consists of a fiber bundle for traditional confocal fluorescence imaging and a single OIR source fiber which is manually redirected at +/- 26 degrees. Diffusely scattered light from each orientation of the source fiber is collected via the fiber bundle, with a frame of data representing spectra collected at a range of distances from the OIR source point. Initial results with intralipid phantoms show good agreement to published data over the 550-650 nm spectral range. We successfully imaged and measured the optical properties of rodent cardiac muscle.

Tensor-driven extraction of developmental features from varying paediatric EEG datasets.

PubMed

Kinney-Lang, Eli; Spyrou, Loukianos; Ebied, Ahmed; Chin, Richard Fm; Escudero, Javier

2018-05-21

Constant changes in developing children's brains can pose a challenge in EEG dependant technologies. Advancing signal processing methods to identify developmental differences in paediatric populations could help improve function and usability of such technologies. Taking advantage of the multi-dimensional structure of EEG data through tensor analysis may offer a framework for extracting relevant developmental features of paediatric datasets. A proof of concept is demonstrated through identifying latent developmental features in resting-state EEG. Approach. Three paediatric datasets (n = 50, 17, 44) were analyzed using a two-step constrained parallel factor (PARAFAC) tensor decomposition. Subject age was used as a proxy measure of development. Classification used support vector machines (SVM) to test if PARAFAC identified features could predict subject age. The results were cross-validated within each dataset. Classification analysis was complemented by visualization of the high-dimensional feature structures using t-distributed Stochastic Neighbour Embedding (t-SNE) maps. Main Results. Development-related features were successfully identified for the developmental conditions of each dataset. SVM classification showed the identified features could accurately predict subject at a significant level above chance for both healthy and impaired populations. t-SNE maps revealed suitable tensor factorization was key in extracting the developmental features. Significance. The described methods are a promising tool for identifying latent developmental features occurring throughout childhood EEG. © 2018 IOP Publishing Ltd.

Making developmental biology relevant to undergraduates in an era of economic rationalism in Australia.

PubMed

Key, Brian; Nurcombe, Victor

2003-01-01

This report describes the road map we followed at our university to accommodate three main factors: financial pressure within the university system; desire to enhance the learning experience of undergraduates; and motivation to increase the prominence of the discipline of developmental biology in our university. We engineered a novel, multi-year undergraduate developmental biology program which was "student-oriented," ensuring that students were continually exposed to the underlying principles and philosophy of this discipline throughout their undergraduate career. Among its key features are introductory lectures in core courses in the first year, which emphasize the relevance of developmental biology to tissue engineering, reproductive medicine, therapeutic approaches in medicine, agriculture and aquaculture. State-of-the-art animated computer graphics and images of high visual impact are also used. In addition, students are streamed into the developmental biology track in the second year, using courses like human embryology and courses shared with cell biology, which include practicals based on modern experimental approaches. Finally, fully dedicated third-year courses in developmental biology are undertaken in conjunction with stand-alone practical courses where students experiencefirst-hand work in a research laboratory. Our philosophy is a "cradle-to-grave" approach to the education of undergraduates so as to prepare highly motivated, enthusiastic and well-educated developmental biologists for entry into graduate programs and ultimately post-doctoral research.

Computational Modeling and Simulation of Developmental ...

EPA Pesticide Factsheets

Standard practice for assessing developmental toxicity is the observation of apical endpoints (intrauterine death, fetal growth retardation, structural malformations) in pregnant rats/rabbits following exposure during organogenesis. EPA’s computational toxicology research program (ToxCast) generated vast in vitro cellular and molecular effects data on >1858 chemicals in >600 high-throughput screening (HTS) assays. The diversity of assays has been increased for developmental toxicity with several HTS platforms, including the devTOX-quickPredict assay from Stemina Biomarker Discovery utilizing the human embryonic stem cell line (H9). Translating these HTS data into higher order-predictions of developmental toxicity is a significant challenge. Here, we address the application of computational systems models that recapitulate the kinematics of dynamical cell signaling networks (e.g., SHH, FGF, BMP, retinoids) in a CompuCell3D.org modeling environment. Examples include angiogenesis (angiodysplasia) and dysmorphogenesis. Being numerically responsive to perturbation, these models are amenable to data integration for systems Toxicology and Adverse Outcome Pathways (AOPs). The AOP simulation outputs predict potential phenotypes based on the in vitro HTS data ToxCast. A heuristic computational intelligence framework that recapitulates the kinematics of dynamical cell signaling networks in the embryo, together with the in vitro profiling data, produce quantitative predic

Signaling molecules involved in the transition of growth to development of Dictyostelium discoideum.

PubMed

Mir, Hina A; Rajawat, Jyotika; Pradhan, Shalmali; Begum, Rasheedunnisa

2007-03-01

The social amoeba Dictyostelium discoideum, a powerful paradigm provides clear insights into the regulation of growth and development. In addition to possessing complex individual cellular functions like a unicellular eukaryote, D. discoideum cells face the challenge of multicellular development. D. discoideum undergoes a relatively simple differentiation process mainly by cAMP mediated pathway. Despite this relative simplicity, the regulatory signaling pathways are as complex as those seen in metazoan development. However, the introduction of restriction-enzyme-mediated integration (REMI) technique to produce developmental gene knockouts has provided novel insights into the discovery of signaling molecules and their role in D. discoideum development. Cell cycle phase is an important aspect for differentiation of D. discoideum, as cells must reach a specific stage to enter into developmental phase and specific cell cycle regulators are involved in arresting growth phase genes and inducing the developmental genes. In this review, we present an overview of the signaling molecules involved in the regulation of growth to differentiation transition (GDT), molecular mechanism of early developmental events leading to generation of cAMP signal and components of cAMP relay system that operate in this paradigm.

Attentional networks in developmental dyscalculia

PubMed Central

2010-01-01

Background Very little is known about attention deficits in developmental dyscalculia, hence, this study was designed to provide the missing information. We examined attention abilities of participants suffering from developmental dyscalculia using the attention networks test - interactions. This test was designed to examine three different attention networks--executive function, orienting and alerting--and the interactions between them. Methods Fourteen university students that were diagnosed as suffering from developmental dyscalculia--intelligence and reading abilities in the normal range and no indication of attention-deficit hyperactivity disorder--and 14 matched controls were tested using the attention networks test - interactions. All participants were given preliminary tests to measure mathematical abilities, reading, attention and intelligence. Results The results revealed deficits in the alerting network--a larger alerting effect--and in the executive function networks--a larger congruity effect in developmental dyscalculia participants. The interaction between the alerting and executive function networks was also modulated by group. In addition, developmental dyscalculia participants were slower to respond in the non-cued conditions. Conclusions These results imply specific attentional deficits in pure developmental dyscalculia. Namely, those with developmental dyscalculia seem to be deficient in the executive function and alertness networks. They suffer from difficulty in recruiting attention, in addition to the deficits in numerical processing. PMID:20157427

Attentional networks in developmental dyscalculia.

PubMed

Askenazi, Sarit; Henik, Avishai

2010-01-07

Very little is known about attention deficits in developmental dyscalculia, hence, this study was designed to provide the missing information. We examined attention abilities of participants suffering from developmental dyscalculia using the attention networks test - interactions. This test was designed to examine three different attention networks--executive function, orienting and alerting--and the interactions between them. Fourteen university students that were diagnosed as suffering from developmental dyscalculia--intelligence and reading abilities in the normal range and no indication of attention-deficit hyperactivity disorder--and 14 matched controls were tested using the attention networks test-interactions. All participants were given preliminary tests to measure mathematical abilities, reading, attention and intelligence. The results revealed deficits in the alerting network--a larger alerting effect--and in the executive function networks--a larger congruity effect in developmental dyscalculia participants. The interaction between the alerting and executive function networks was also modulated by group. In addition, developmental dyscalculia participants were slower to respond in the non-cued conditions. These results imply specific attentional deficits in pure developmental dyscalculia. Namely, those with developmental dyscalculia seem to be deficient in the executive function and alertness networks. They suffer from difficulty in recruiting attention, in addition to the deficits in numerical processing.

Tracking and Quantifying Developmental Processes in C. elegans Using Open-source Tools.

PubMed

Dutta, Priyanka; Lehmann, Christina; Odedra, Devang; Singh, Deepika; Pohl, Christian

2015-12-16

Quantitatively capturing developmental processes is crucial to derive mechanistic models and key to identify and describe mutant phenotypes. Here protocols are presented for preparing embryos and adult C. elegans animals for short- and long-term time-lapse microscopy and methods for tracking and quantification of developmental processes. The methods presented are all based on C. elegans strains available from the Caenorhabditis Genetics Center and on open-source software that can be easily implemented in any laboratory independently of the microscopy system used. A reconstruction of a 3D cell-shape model using the modelling software IMOD, manual tracking of fluorescently-labeled subcellular structures using the multi-purpose image analysis program Endrov, and an analysis of cortical contractile flow using PIVlab (Time-Resolved Digital Particle Image Velocimetry Tool for MATLAB) are shown. It is discussed how these methods can also be deployed to quantitatively capture other developmental processes in different models, e.g., cell tracking and lineage tracing, tracking of vesicle flow.

Distinguishing between biochemical and cellular function: Are there peptide signatures for cellular function of proteins?

PubMed

Jain, Shruti; Bhattacharyya, Kausik; Bakshi, Rachit; Narang, Ankita; Brahmachari, Vani

2017-04-01

The genome annotation and identification of gene function depends on conserved biochemical activity. However, in the cell, proteins with the same biochemical function can participate in different cellular pathways and cannot complement one another. Similarly, two proteins of very different biochemical functions are put in the same class of cellular function; for example, the classification of a gene as an oncogene or a tumour suppressor gene is not related to its biochemical function, but is related to its cellular function. We have taken an approach to identify peptide signatures for cellular function in proteins with known biochemical function. ATPases as a test case, we classified ATPases (2360 proteins) and kinases (517 proteins) from the human genome into different cellular function categories such as transcriptional, replicative, and chromatin remodelling proteins. Using publicly available tool, MEME, we identify peptide signatures shared among the members of a given category but not between cellular functional categories; for example, no motif sharing is seen between chromatin remodelling and transporter ATPases, similarly between receptor Serine/Threonine Kinase and Receptor Tyrosine Kinase. There are motifs shared within each category with significant E value and high occurrence. This concept of signature for cellular function was applied to developmental regulators, the polycomb and trithorax proteins which led to the prediction of the role of INO80, a chromatin remodelling protein, in development. This has been experimentally validated earlier for its role in homeotic gene regulation and its interaction with regulatory complexes like the Polycomb and Trithorax complex. Proteins 2017; 85:682-693. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Cellular and laminar expression of Dab-1 during the postnatal critical period in cat visual cortex and the effects of dark rearing.

PubMed

Kiser, Paul J; Liu, Zijing; Wilt, Steven D; Mower, George D

2011-04-06

This study describes postnatal critical period changes in cellular and laminar expression of Dab-1, a gene shown to play a role in controlling neuronal positioning during embryonic brain development, in cat visual cortex and the effects of dark rearing (DR). At 1week, there is dense cellular staining which is uniform across cortical layers and very light neuropil staining. At the peak of the critical period (5weeks), dense cell staining is largely restricted to large pyramidal cells of deep layer III and layer V, there is faint cell body staining throughout all cortical layers, neuropil staining is markedly increased and uniform in layers III to VI. This dramatic change in laminar and cellular labeling is independent of visual input, since immunostaining is similar in 5-week DR cats. By 10weeks, the mature laminar and cellular staining pattern is established and the major subsequent change is a further reduction in the density of cellular staining in all cortical layers. Neuropil staining is pronounced and uniform across cortical layers. These developmental changes are altered by DR. Quantification by cell counts indicated that age and DR interact such that differences in cellular expression are opposite in direction between 5- and 20-week-old cats. This bidirectional regulation of cellular expression is the same in all cortical laminae. The bidirectional regulation of cellular expression matches the effects of age and DR on physiological plasticity during the critical period as assessed by ocular dominance shifts in response to monocular deprivation. Copyright © 2011 Elsevier B.V. All rights reserved.

The never-ending story: from pluripotency to plant developmental plasticity

PubMed Central

Gaillochet, Christophe; Lohmann, Jan U.

2015-01-01

Plants are sessile organisms, some of which can live for over a thousand years. Unlike most animals, plants employ a post-embryonic mode of development driven by the continuous activity of pluripotent stem cells. Consequently, plants are able to initiate new organs over extended periods of time, and many species can readily replace lost body structures by de novo organogenesis. Classical studies have also shown that plant tissues have a remarkable capacity to undergo de-differentiation and proliferation in vitro, highlighting the fact that plant cell fate is highly plastic. This suggests that the mechanisms regulating fate transitions must be continuously active in most plant cells and that the control of cellular pluripotency lies at the core of diverse developmental programs. Here, we review how pluripotency is established in plant stem cell systems, how it is maintained during development and growth and re-initiated during regeneration, and how these mechanisms eventually contribute to the amazing developmental plasticity of plants. PMID:26130755

Dynamic CRM occupancy reflects a temporal map of developmental progression.

PubMed

Wilczyński, Bartek; Furlong, Eileen E M

2010-06-22

Development is driven by tightly coordinated spatio-temporal patterns of gene expression, which are initiated through the action of transcription factors (TFs) binding to cis-regulatory modules (CRMs). Although many studies have investigated how spatial patterns arise, precise temporal control of gene expression is less well understood. Here, we show that dynamic changes in the timing of CRM occupancy is a prevalent feature common to all TFs examined in a developmental ChIP time course to date. CRMs exhibit complex binding patterns that cannot be explained by the sequence motifs or expression of the TFs themselves. The temporal changes in TF binding are highly correlated with dynamic patterns of target gene expression, which in turn reflect transitions in cellular function during different stages of development. Thus, it is not only the timing of a TF's expression, but also its temporal occupancy in refined time windows, which determines temporal gene expression. Systematic measurement of dynamic CRM occupancy may therefore serve as a powerful method to decode dynamic changes in gene expression driving developmental progression.

Knockdown of zebrafish Fancd2 causes developmental abnormalities via p53-dependent apoptosis.

PubMed

Liu, Ting Xi; Howlett, Niall G; Deng, Min; Langenau, David M; Hsu, Karl; Rhodes, Jennifer; Kanki, John P; D'Andrea, Alan D; Look, A Thomas

2003-12-01

Mechanisms underlying the multiple developmental defects observed in Fanconi anemia (FA) patients are not well defined. We have identified the zebrafish homolog of human FANCD2, which encodes a nuclear effector protein that is monoubiquitinated in response to DNA damage, targeting it to nuclear foci where it preserves chromosomal integrity. Fancd2-deficient zebrafish embryos develop defects similar to those found in children with FA, including shortened body length, microcephaly, and microophthalmia, which are due to extensive cellular apoptosis. Developmental defects and increased apoptosis in Fancd2-deficient zebrafish were corrected by injection of human FANCD2 or zebrafish bcl2 mRNA, or by knockdown of p53, indicating that in the absence of Fancd2, developing tissues spontaneously undergo p53-dependent apoptosis. Thus, Fancd2 is essential during embryogenesis to prevent inappropriate apoptosis in neural cells and other tissues undergoing high levels of proliferative expansion, implicating this mechanism in the congenital abnormalities observed in human infants with FA.

Programmed cell senescence during mammalian embryonic development.

PubMed

Muñoz-Espín, Daniel; Cañamero, Marta; Maraver, Antonio; Gómez-López, Gonzalo; Contreras, Julio; Murillo-Cuesta, Silvia; Rodríguez-Baeza, Alfonso; Varela-Nieto, Isabel; Ruberte, Jesús; Collado, Manuel; Serrano, Manuel

2013-11-21

Cellular senescence disables proliferation in damaged cells, and it is relevant for cancer and aging. Here, we show that senescence occurs during mammalian embryonic development at multiple locations, including the mesonephros and the endolymphatic sac of the inner ear, which we have analyzed in detail. Mechanistically, senescence in both structures is strictly dependent on p21, but independent of DNA damage, p53, or other cell-cycle inhibitors, and it is regulated by the TGF-β/SMAD and PI3K/FOXO pathways. Developmentally programmed senescence is followed by macrophage infiltration, clearance of senescent cells, and tissue remodeling. Loss of senescence due to the absence of p21 is partially compensated by apoptosis but still results in detectable developmental abnormalities. Importantly, the mesonephros and endolymphatic sac of human embryos also show evidence of senescence. We conclude that the role of developmentally programmed senescence is to promote tissue remodeling and propose that this is the evolutionary origin of damage-induced senescence. Copyright © 2013 Elsevier Inc. All rights reserved.

Thinking Developmentally: The Next Evolution in Models of Health.

PubMed

Garner, Andrew S

2016-09-01

As the basic sciences that inform conceptions of human health advance, so must the models that are used to frame additional research, to teach the next generation of providers, and to inform health policy. This article briefly reviews the evolution from a biomedical model to a biopsychosocial (BPS) model and to an ecobiodevelopmental (EBD) model. Like the BPS model, the EBD model reaffirms the biological significance of psychosocial features within the patient's ecology, but it does so at the molecular and cellular levels. More importantly, the EBD model adds the dimension of time, forcing providers to "think developmentally" and to acknowledge the considerable biological and psychological consequences of previous experiences. For the health care system to move from a reactive "sick care" system to a proactive "well care" system, all providers must begin thinking developmentally by acknowledging the dynamic but cumulative dance between nature and nurture that drives development, behavior, and health, not only in childhood, but across the lifespan.

Neurogliaform cortical interneurons derive from cells in the preoptic area

PubMed Central

Cadilhac, Christelle; Prados, Julien; Holtmaat, Anthony

2018-01-01

Delineating the basic cellular components of cortical inhibitory circuits remains a fundamental issue in order to understand their specific contributions to microcircuit function. It is still unclear how current classifications of cortical interneuron subtypes relate to biological processes such as their developmental specification. Here we identified the developmental trajectory of neurogliaform cells (NGCs), the main effectors of a powerful inhibitory motif recruited by long-range connections. Using in vivo genetic lineage-tracing in mice, we report that NGCs originate from a specific pool of 5-HT3AR-expressing Hmx3+ cells located in the preoptic area (POA). Hmx3-derived 5-HT3AR+ cortical interneurons (INs) expressed the transcription factors PROX1, NR2F2, the marker reelin but not VIP and exhibited the molecular, morphological and electrophysiological profile of NGCs. Overall, these results indicate that NGCs are a distinct class of INs with a unique developmental trajectory and open the possibility to study their specific functional contribution to cortical inhibitory microcircuit motifs. PMID:29557780

Decoding the Regulatory Network for Blood Development from Single-Cell Gene Expression Measurements

PubMed Central

Haghverdi, Laleh; Lilly, Andrew J.; Tanaka, Yosuke; Wilkinson, Adam C.; Buettner, Florian; Macaulay, Iain C.; Jawaid, Wajid; Diamanti, Evangelia; Nishikawa, Shin-Ichi; Piterman, Nir; Kouskoff, Valerie; Theis, Fabian J.; Fisher, Jasmin; Göttgens, Berthold

2015-01-01

Here we report the use of diffusion maps and network synthesis from state transition graphs to better understand developmental pathways from single cell gene expression profiling. We map the progression of mesoderm towards blood in the mouse by single-cell expression analysis of 3,934 cells, capturing cells with blood-forming potential at four sequential developmental stages. By adapting the diffusion plot methodology for dimensionality reduction to single-cell data, we reconstruct the developmental journey to blood at single-cell resolution. Using transitions between individual cellular states as input, we develop a single-cell network synthesis toolkit to generate a computationally executable transcriptional regulatory network model that recapitulates blood development. Model predictions were validated by showing that Sox7 inhibits primitive erythropoiesis, and that Sox and Hox factors control early expression of Erg. We therefore demonstrate that single-cell analysis of a developing organ coupled with computational approaches can reveal the transcriptional programs that control organogenesis. PMID:25664528

47 CFR 2.805 - Operation of radio frequency products prior to equipment authorization.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Evaluation of performance and determination of customer acceptability, during developmental, design, or pre... performance and determination of customer acceptability, during developmental, design, or pre-production... under the authority of an experimental radio service authorization issued under part 5 of this chapter...

Mini Review: Biomaterials for Enhancing Neuronal Repair

NASA Astrophysics Data System (ADS)

Cangellaris, Olivia V.; Gillette, Martha U.

2018-04-01

As they differentiate from neuroblasts, nascent neurons become highly polarized and elongate. Neurons extend and elaborate fine and fragile cellular extensions that form circuits enabling long-distance communication and signal integration within the body. While other organ systems are developing, projections of differentiating neurons find paths to distant targets. Subsequent post-developmental neuronal damage is catastrophic because the cues for reinnervation are no longer active. Advances in biomaterials are enabling fabrication of micro-environments that encourage neuronal regrowth and restoration of function by recreating these developmental cues. This mini-review considers new materials that employ topographical, chemical, electrical, and/or mechanical cues for use in neuronal repair. Manipulating and integrating these elements in different combinations will generate new technologies to enhance neural repair.

Whole-Cell Electrical Activity Under Direct Mechanical Stimulus by AFM Cantilever Using Planar Patch Clamp Chip Approach

PubMed Central

Upadhye, Kalpesh V.; Candiello, Joseph E.; Davidson, Lance A.; Lin, Hai

2011-01-01

Patch clamp is a powerful tool for studying the properties of ion-channels and cellular membrane. In recent years, planar patch clamp chips have been fabricated from various materials including glass, quartz, silicon, silicon nitride, polydimethyl-siloxane (PDMS), and silicon dioxide. Planar patch clamps have made automation of patch clamp recordings possible. However, most planar patch clamp chips have limitations when used in combination with other techniques. Furthermore, the fabrication methods used are often expensive and require specialized equipments. An improved design as well as fabrication and characterization of a silicon-based planar patch clamp chip are described in this report. Fabrication involves true batch fabrication processes that can be performed in most common microfabrication facilities using well established MEMS techniques. Our planar patch clamp chips can form giga-ohm seals with the cell plasma membrane with success rate comparable to existing patch clamp techniques. The chip permits whole-cell voltage clamp recordings on variety of cell types including Chinese Hamster Ovary (CHO) cells and pheochromocytoma (PC12) cells, for times longer than most available patch clamp chips. When combined with a custom microfluidics chamber, we demonstrate that it is possible to perfuse the extra-cellular as well as intra-cellular buffers. The chamber design allows integration of planar patch clamp with atomic force microscope (AFM). Using our planar patch clamp chip and microfluidics chamber, we have recorded whole-cell mechanosensitive (MS) currents produced by directly stimulating human keratinocyte (HaCaT) cells using an AFM cantilever. Our results reveal the spatial distribution of MS ion channels and temporal details of the responses from MS channels. The results show that planar patch clamp chips have great potential for multi-parametric high throughput studies of ion channel proteins. PMID:22174731

Effects of ordinary and adaptive toys on pre-school children with developmental disabilities.

PubMed

Hsieh, Hsieh-Chun

2008-01-01

Toys help children in mastering developmental tasks. This study investigated toy effect on children with developmental disabilities as they engage in using ordinary and adaptive toys. A single-subject design was used to identify the effects on their toy play abilities. Differences in toy effects between playing ordinary and adaptive toys were examined. Three special education teachers chose ordinary toys and modified ordinary toys. Modified ordinary toys, i.e., adaptive toys, were designed according to the individual disabilities of participating children, treatment goals, and the toy types. Three children with developmental disabilities from pre-schools in Taiwan were enrolled. Appropriate participation of three pre-schoolers increased dramatically in playing adaptive toys during intervention phase. The toy effects demonstrate that when using adaptive toys, children with developmental disabilities may response better during toy play sessions.

Developing multi-cellular tumor spheroid model (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening.

PubMed

Wang, Jian-Zheng; Zhu, Yu-Xia; Ma, Hui-Chao; Chen, Si-Nan; Chao, Ji-Ye; Ruan, Wen-Ding; Wang, Duo; Du, Feng-guang; Meng, Yue-Zhong

2016-05-01

In this work, a 3D MCTS-CCA system was constructed by culturing multi-cellular tumor spheroid (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening. The CCA scaffolds were fabricated by spray-spinning. The interactions between the components of the spray-spun fibers were evidenced by methods of Coomassie Blue stain, X-ray diffraction (XRD) and Fourier transform-infrared spectroscopy (FTIR). Co-culture indicated that MCF-7 cells showed a spatial growth pattern of multi-cellular tumor spheroid (MCTS) in the CCA fibrous scaffold with increased proliferation rate and drug-resistance to MMC, ADM and 5-Aza comparing with the 2D culture cells. Significant increases of total viable cells were found in 3D MCTS groups after drug administration by method of apoptotic analysis. Glucose-lactate analysis indicated that the metabolism of MCTS in CCA scaffold was closer to the tumor issue in vivo than the monolayer cells. In addition, MCTS showed the characteristic of epithelial mesenchymal transition (EMT) which is subverted by carcinoma cells to facilitate metastatic spread. These results demonstrated that MCTS in CCA scaffold possessed a more conservative phenotype of tumor than monolayer cells, and anticancer drug screening in 3D MCTS-CCA system might be superior to the 2D culture system. Copyright © 2016 Elsevier B.V. All rights reserved.

A tool for multi-scale modelling of the renal nephron

PubMed Central

Nickerson, David P.; Terkildsen, Jonna R.; Hamilton, Kirk L.; Hunter, Peter J.

2011-01-01

We present the development of a tool, which provides users with the ability to visualize and interact with a comprehensive description of a multi-scale model of the renal nephron. A one-dimensional anatomical model of the nephron has been created and is used for visualization and modelling of tubule transport in various nephron anatomical segments. Mathematical models of nephron segments are embedded in the one-dimensional model. At the cellular level, these segment models use models encoded in CellML to describe cellular and subcellular transport kinetics. A web-based presentation environment has been developed that allows the user to visualize and navigate through the multi-scale nephron model, including simulation results, at the different spatial scales encompassed by the model description. The Zinc extension to Firefox is used to provide an interactive three-dimensional view of the tubule model and the native Firefox rendering of scalable vector graphics is used to present schematic diagrams for cellular and subcellular scale models. The model viewer is embedded in a web page that dynamically presents content based on user input. For example, when viewing the whole nephron model, the user might be presented with information on the various embedded segment models as they select them in the three-dimensional model view. Alternatively, the user chooses to focus the model viewer on a cellular model located in a particular nephron segment in order to view the various membrane transport proteins. Selecting a specific protein may then present the user with a description of the mathematical model governing the behaviour of that protein—including the mathematical model itself and various simulation experiments used to validate the model against the literature. PMID:22670210

The Development of Risk-Taking: A Multi-Perspective Review

ERIC Educational Resources Information Center

Boyer, Ty W.

2006-01-01

The current paper reviews four research perspectives that have been used to investigate the development of risk-taking. Cognitive developmental research has investigated the development of decision-making capacities that potentially underlie risk-taking development, including sensitivity to risk, probability estimation, and perceptions of…

In vivo cell biology in zebrafish - providing insights into vertebrate development and disease.

PubMed

Vacaru, Ana M; Unlu, Gokhan; Spitzner, Marie; Mione, Marina; Knapik, Ela W; Sadler, Kirsten C

2014-02-01

Over the past decades, studies using zebrafish have significantly advanced our understanding of the cellular basis for development and human diseases. Zebrafish have rapidly developing transparent embryos that allow comprehensive imaging of embryogenesis combined with powerful genetic approaches. However, forward genetic screens in zebrafish have generated unanticipated findings that are mirrored by human genetic studies: disruption of genes implicated in basic cellular processes, such as protein secretion or cytoskeletal dynamics, causes discrete developmental or disease phenotypes. This is surprising because many processes that were assumed to be fundamental to the function and survival of all cell types appear instead to be regulated by cell-specific mechanisms. Such discoveries are facilitated by experiments in whole animals, where zebrafish provides an ideal model for visualization and manipulation of organelles and cellular processes in a live vertebrate. Here, we review well-characterized mutants and newly developed tools that underscore this notion. We focus on the secretory pathway and microtubule-based trafficking as illustrative examples of how studying cell biology in vivo using zebrafish has broadened our understanding of the role fundamental cellular processes play in embryogenesis and disease.

Effects of Silver and Other Metals on the Cytoskeleton

NASA Technical Reports Server (NTRS)

Conrad, Gary W.

1997-01-01

Directly or indirectly, trace concentrations of silver ion (Ag(+)) stabilize microtubules (Conrad, A.H., et al. Cell Motil. & Cytoskel. 27:117-132), as does taxol (Conrad, A.H., et al. J. Exp. Zool. 262:154-165), an effect with major consequences for cellular shape changes and development. Polymerization of microtubules is gravity-sensitive (Tabony and Job, Proc. Natl. Acad. Sci. USA 89:6948-6952), so trace amounts of Ag(+) may alter cellular ability to respond to gravity. If Ag electrolysis is used to purify water on NASA space vehicles, plants and animals/astronauts will be exposed continuously to Ag(+), a regimen with unknown cellular and developmental consequences. Fertilized eggs of the marine mudsnail, Ilyanassa obsoleta, are the cells in which the effects of A(+) on microtubules were discovered. They distribute visible cytoplasmic contents according to gravity and contain cytoplasmic morphogenetic determinants for heart development. The objectives are to determine if the effects of Ag(+), AU(3+), (of biosensor relevance), or Gd(3+) (inhibitor of some stretch-activated ion channels) on the cytoskeleton (in the presence and absence of mechanical loading) will affect cellular responses to gravity.