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

G-quadruplex in animal development: Contribution to gene expression and genomic heterogeneity.

PubMed

Armas, Pablo; Calcaterra, Nora Beatriz

2018-05-18

During animal development, gene expression is orchestrated by specific and highly evolutionarily conserved mechanisms that take place accurately, both at spatial and temporal levels. The last decades have provided compelling evidence showing that chromatin state plays essential roles in orchestrating most of the stages of development. The DNA molecule can adopt alternative structures different from the helical duplex architecture. G-rich DNA sequences can fold as intrastrand quadruple helix structures called G-quadruplexes or G4-DNA. G4 can also be formed in RNA molecules, such as mRNA, lncRNA and pre-miRNA. Emerging evidences suggest that G4s have crucial roles in a variety of biological processes, including transcription, recombination, replication, translation and chromosome stability. In this review, we have collected recent information gathered by various laboratories showing the important role of G4 DNA and RNA structures in several steps of animal development. Copyright © 2018 Elsevier B.V. All rights reserved.

Hospitals' strategies for orchestrating selection of physician preference items.

PubMed

Montgomery, Kathleen; Schneller, Eugene S

2007-06-01

This article analyzes hospitals' strategies to shape physicians' behavior and counter suppliers' power in purchasing physician preference items. Two models of standardization are limitations on the range of manufacturers or products (the "formulary" model) and price ceilings for particular item categories (the "payment-cap" model), both requiring processes to define product equivalencies often with inadequate product comparison data. The formulary model is more difficult to implement because of physicians' resistance to top-down dictates. The payment-cap model is more feasible because it preserves physicians' choice while also restraining manufacturers' power. Hospitals may influence physicians' involvement through a process of orchestration that includes committing to improve clinical facilities, scheduling, and training and fostering a culture of mutual trust and respect.

Hospitals' Strategies for Orchestrating Selection of Physician Preference Items

PubMed Central

Montgomery, Kathleen; Schneller, Eugene S

2007-01-01

This article analyzes hospitals' strategies to shape physicians' behavior and counter suppliers' power in purchasing physician preference items. Two models of standardization are limitations on the range of manufacturers or products (the “formulary” model) and price ceilings for particular item categories (the “payment-cap” model), both requiring processes to define product equivalencies often with inadequate product comparison data. The formulary model is more difficult to implement because of physicians' resistance to top-down dictates. The payment-cap model is more feasible because it preserves physicians' choice while also restraining manufacturers' power. Hospitals may influence physicians' involvement through a process of orchestration that includes committing to improve clinical facilities, scheduling, and training and fostering a culture of mutual trust and respect. PMID:17517118

Semantic orchestration of image processing services for environmental analysis

NASA Astrophysics Data System (ADS)

Ranisavljević, Élisabeth; Devin, Florent; Laffly, Dominique; Le Nir, Yannick

2013-09-01

In order to analyze environmental dynamics, a major process is the classification of the different phenomena of the site (e.g. ice and snow for a glacier). When using in situ pictures, this classification requires data pre-processing. Not all the pictures need the same sequence of processes depending on the disturbances. Until now, these sequences have been done manually, which restricts the processing of large amount of data. In this paper, we present how to realize a semantic orchestration to automate the sequencing for the analysis. It combines two advantages: solving the problem of the amount of processing, and diversifying the possibilities in the data processing. We define a BPEL description to express the sequences. This BPEL uses some web services to run the data processing. Each web service is semantically annotated using an ontology of image processing. The dynamic modification of the BPEL is done using SPARQL queries on these annotated web services. The results obtained by a prototype implementing this method validate the construction of the different workflows that can be applied to a large number of pictures.

Light Controlled Modulation of Gene Expression by Chemical Optoepigenetic Probes

PubMed Central

Reis, Surya A.; Ghosh, Balaram; Hendricks, J. Adam; Szantai-Kis, D. Miklos; Törk, Lisa; Ross, Kenneth N.; Lamb, Justin; Read-Button, Willis; Zheng, Baixue; Wang, Hongtao; Salthouse, Christopher; Haggarty, Stephen J.; Mazitschek, Ralph

2016-01-01

Epigenetic gene regulation is a dynamic process orchestrated by chromatin-modifying enzymes. Many of these master regulators exert their function through covalent modification of DNA and histone proteins. Aberrant epigenetic processes have been implicated in the pathophysiology of multiple human diseases. Small-molecule inhibitors have been essential to advancing our understanding of the underlying molecular mechanisms of epigenetic processes. However, the resolution offered by small molecules is often insufficient to manipulate epigenetic processes with high spatio-temporal control. Here, we present a novel and generalizable approach, referred to as ‘Chemo-Optical Modulation of Epigenetically-regulated Transcription’ (COMET), enabling high-resolution, optical control of epigenetic mechanisms based on photochromic inhibitors of human histone deacetylases using visible light. COMET probes may translate into novel therapeutic strategies for diseases where conditional and selective epigenome modulation is required. PMID:26974814

Integrated Business Process Adaptation towards Friction-Free Business-to-Business Collaboration

ERIC Educational Resources Information Center

Shan, Zhe

2011-01-01

One key issue in process-aware E-commerce collaboration is the orchestration of business processes of multiple business partners throughout a supply chain network in an automated and seamless way. Since each partner has its own internal processes with different control flow structures and message interfaces, the real challenge lies in verifying…

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.

Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release

PubMed Central

Venereau, Emilie; Casalgrandi, Maura; Schiraldi, Milena; Antoine, Daniel J.; Cattaneo, Angela; De Marchis, Francesco; Liu, Jaron; Antonelli, Antonella; Preti, Alessandro; Raeli, Lorenzo; Shams, Sara Samadi; Yang, Huan; Varani, Luca; Andersson, Ulf; Tracey, Kevin J.; Bachi, Angela; Uguccioni, Mariagrazia

2012-01-01

Tissue damage causes inflammation, by recruiting leukocytes and activating them to release proinflammatory mediators. We show that high-mobility group box 1 protein (HMGB1) orchestrates both processes by switching among mutually exclusive redox states. Reduced cysteines make HMGB1 a chemoattractant, whereas a disulfide bond makes it a proinflammatory cytokine and further cysteine oxidation to sulfonates by reactive oxygen species abrogates both activities. We show that leukocyte recruitment and activation can be separated. A nonoxidizable HMGB1 mutant in which serines replace all cysteines (3S-HMGB1) does not promote cytokine production, but is more effective than wild-type HMGB1 in recruiting leukocytes in vivo. BoxA, a HMGB1 inhibitor, interferes with leukocyte recruitment but not with activation. We detected the different redox forms of HMGB1 ex vivo within injured muscle. HMGB1 is completely reduced at first and disulfide-bonded later. Thus, HMGB1 orchestrates both key events in sterile inflammation, leukocyte recruitment and their induction to secrete inflammatory cytokines, by adopting mutually exclusive redox states. PMID:22869893

Metacognitive Awareness and Monitoring in Adult and College Readers.

ERIC Educational Resources Information Center

Rinehart, Steve D.; Platt, Jennifer M.

1984-01-01

A literature review was undertaken to demonstrate how knowledge of one's cognitive processes, the orchestration of strategic effort, and the monitoring of one's cognitive activities can enhance reading performance. The findings indicate that while older readers exercise more awareness of their own learning processes and greater self-control or…

Methodological Reflections: Designing and Understanding Computer-Supported Collaborative Learning

ERIC Educational Resources Information Center

Hamalainen, Raija

2012-01-01

Learning involves more than just a small group of participants, which makes designing and managing collaborative learning processes in higher education a challenging task. As a result, emerging concerns in current research have pointed increasingly to teacher orchestrated learning processes in naturalistic learning settings. In line with this…

Nuclear Organization in the Spinal Cord Depends on Motor Neuron Lamination Orchestrated by Catenin and Afadin Function.

PubMed

Dewitz, Carola; Pimpinella, Sofia; Hackel, Patrick; Akalin, Altuna; Jessell, Thomas M; Zampieri, Niccolò

2018-02-13

Motor neurons in the spinal cord are found grouped in nuclear structures termed pools, whose position is precisely orchestrated during development. Despite the emerging role of pool organization in the assembly of spinal circuits, little is known about the morphogenetic programs underlying the patterning of motor neuron subtypes. We applied three-dimensional analysis of motor neuron position to reveal the roles and contributions of cell adhesive function by inactivating N-cadherin, catenin, and afadin signaling. Our findings reveal that nuclear organization of motor neurons is dependent on inside-out positioning, orchestrated by N-cadherin, catenin, and afadin activities, controlling cell body layering on the medio-lateral axis. In addition to this lamination-like program, motor neurons undergo a secondary, independent phase of organization. This process results in segregation of motor neurons along the dorso-ventral axis of the spinal cord, does not require N-cadherin or afadin activity, and can proceed even when medio-lateral positioning is perturbed. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Retrograde Signals: Integrators of Interorganellar Communication and Orchestrators of Plant Development.

PubMed

de Souza, Amancio; Wang, Jin-Zheng; Dehesh, Katayoon

2017-04-28

Interorganellar cooperation maintained via exquisitely controlled retrograde-signaling pathways is an evolutionary necessity for maintenance of cellular homeostasis. This signaling feature has therefore attracted much research attention aimed at improving understanding of the nature of these communication signals, how the signals are sensed, and ultimately the mechanism by which they integrate targeted processes that collectively culminate in organellar cooperativity. The answers to these questions will provide insight into how retrograde-signal-mediated regulatory mechanisms are recruited and which biological processes are targeted, and will advance our understanding of how organisms balance metabolic investments in growth against adaptation to environmental stress. This review summarizes the present understanding of the nature and the functional complexity of retrograde signals as integrators of interorganellar communication and orchestrators of plant development, and offers a perspective on the future of this critical and dynamic area of research.

Photoperiod length paces the temporal orchestration of cell cycle and carbon-nitrogen metabolism in Crocosphaera watsonii.

PubMed

Dron, Anthony; Rabouille, Sophie; Claquin, Pascal; Talec, Amélie; Raimbault, Virginie; Sciandra, Antoine

2013-12-01

We analysed the effect of photoperiod length (PPL) (16:8 and 8:16 h of light-dark regime, named long and short PPL, respectively) on the temporal orchestration of the two antagonistic, carbon and nitrogen acquisitions in the unicellular, diazotrophic cyanobacterium Crocosphaera watsonii strain WH8501 growing diazotrophically. Carbon and nitrogen metabolism were monitored at high frequency, and their patterns were compared with the cell cycle progression. The oxygen-sensitive N2 fixation process occurred mainly during the dark period, where photosynthesis cannot take place, inducing a light-dark cycle of cellular C : N ratio. Examination of circadian patterns in the cell cycle revealed that cell division occurred during the midlight period, (8 h and 4 h into the light in the long and short PPL conditions, respectively), thus timely separated from the energy-intensive diazotrophic process. Results consistently show a nearly 5 h time lag between the end of cell division and the onset of N2 fixation. Shorter PPLs affected DNA compaction of C. watsonii cells and also led to a decrease in the cell division rate. Therefore, PPL paces the growth of C. watsonii: a long PPL enhances cell division while a short PPL favours somatic growth (biomass production) with higher carbon and nitrogen cell contents. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

An Exploratory Comparison of Novice, Intermediate, and Expert Orchestral Conductors

ERIC Educational Resources Information Center

Bergee, Martin J.

2005-01-01

This study compared novice, "intermediate" (graduate student), and expert orchestral conductors. Two novice conductors, one graduate student in orchestral conducting, and one expert conductor led a university symphony orchestra in part of the first movement of Brahms's Symphony No. 2. Wired for sound, conductors attempted to verbalize their…

Orchestral Performance and the Footprint of Mindfulness

ERIC Educational Resources Information Center

Langer, Ellen; Russell, Timothy; Eisenkraft, Noah

2009-01-01

Two studies were designed to test the hypothesis that actively creating novel distinctions and sonically portraying them during the performance of orchestral music is preferable to attempting to re-create a past performance. The data suggest that orchestral musicians preferred creating music when they were encouraged to mindfully incorporate…

A Young Person's Guide to the Orchestral Profession

ERIC Educational Resources Information Center

Corkhill, David

2005-01-01

Through interviews with ten conservatoire students and ten professional orchestral musicians teaching at conservatoires, this paper seeks to establish whether young people regard the orchestral music profession as a worthwhile ambition. If so, are teachers preparing students sufficiently for their careers and passing on the benefits of their…

The Effects of Orchestration on Musicians' and Nonmusicians' Perception of Musical Tension

ERIC Educational Resources Information Center

Silvey, Brian A.

2011-01-01

The purpose of this study was to examine the effects of orchestration on musicians' and nonmusicians' (N = 40) perception of musical tension. Participants were asked to register their perceptions of tension using the Continuous Response Digital Interface dial while listening to three orchestrations (full orchestra, brass quintet, and solo piano)…

Technology-Supported Orchestration Matters: Outperforming Paper-Based Scripting in a Jigsaw Classroom

ERIC Educational Resources Information Center

Balestrini, Mara; Hernandez-Leo, Davinia; Nieves, Raul; Blat, Josep

2014-01-01

Under the umbrella of ubiquitous technologies, many computational artifacts have been designed to enhance the learning experience in physical settings such as classrooms or playgrounds, but few of them focus on aiding orchestration. This paper presents a systematic evaluation of the signal orchestration system (SOS) used by students for a jigsaw…

Open-Source, Distributed Computational Environment for Virtual Materials Exploration

DTIC Science & Technology

2015-01-01

compromising structural integrity.  For  example, advanced designs could specify advanced materials processing techniques such as heat  treatments  in specific...orchestration of execution of multiple standalone codes at varying  length scales will need advanced  high ‐performance computing (HPC) integration in...possible hooks that could be used to  coordinate larger  workflows spanning tools developed by different groups.    The  high  level approach explored

Implementation Recommendations for MOSAIC: A Workflow Architecture for Analytic Enrichment. Analysis and Recommendations for the Implementation of a Cohesive Method for Orchestrating Analytics in a Distributed Model

DTIC Science & Technology

2011-02-01

Process Architecture Technology Analysis: Executive .............................................. 15 UIMA as Executive...44 A.4: Flow Code in UIMA ......................................................................................................... 46... UIMA ................................................................................................................................ 57 E.2

Understanding Business Analytics

DTIC Science & Technology

2015-01-05

analytics have been used in organizations for a variety of reasons for quite some time; ranging from the simple (generating and understanding business analytics...process. understanding business analytics 3 How well these two components are orchestrated will determine the level of success an organization has in

Innate control of adaptive immunity: Beyond the three-signal paradigm

PubMed Central

Jain, Aakanksha; Pasare, Chandrashekhar

2017-01-01

Activation of cells in the adaptive immune system is a highly orchestrated process dictated by multiples cues from the innate immune system. Although the fundamental principles of innate control of adaptive immunity are well established, it is not fully understood how innate cells integrate qualitative pathogenic information in order to generate tailored protective adaptive immune responses. In this review, we discuss complexities involved in the innate control of adaptive immunity that extend beyond T cell receptor engagement, co-stimulation and priming cytokine production but are critical for generation of protective T cell immunity. PMID:28483987

Novel Mechanisms of Herbal Therapies for Inhibiting HMGB1 Secretion or Action

PubMed Central

Wu, Andrew H.; He, Li; Long, Wei; Zhou, Qiuping; Zhu, Shu; Wang, Ping; Fan, Saijun; Wang, Haichao

2015-01-01

High mobility group box 1 (HMGB1) is an evolutionarily conserved protein and is constitutively expressed in virtually all types of cells. In response to microbial infections, HMGB1 is secreted from activated immune cells to orchestrate rigorous inflammatory responses. Here we review the distinct mechanisms by which several herbal components inhibit HMGB1 action or secretion, such as by modulating inflammasome activation, autophagic degradation, or endocytic uptake. In light of the reciprocal interactions between these cellular processes, it is possible to develop more effective combinational herbal therapies for the clinical management of inflammatory diseases. PMID:25821489

A Study of Master's Degrees in Orchestral Conducting in the United States

ERIC Educational Resources Information Center

St. John, Brian Allen

2010-01-01

In order to learn to be an orchestra conductor in the United States of America, students often begins their formal education by seeking to earn a master's degree in orchestral conducting. This project compiled a listing of American universities which offer a master's degree in orchestral conducting and categorized the component parts of their…

Engaging with Mathematics in the Kindergarten. Orchestrating a Fairy Tale through Questioning and Use of Tools

ERIC Educational Resources Information Center

Carlsen, Martin

2013-01-01

The aim of this study is to analyse how a kindergarten teacher orchestrated a mathematical activity involving a fairy tale. Taking a sociocultural perspective on learning and development, naturally occurring talk-in-interaction has been analysed in order to scrutinise the subtleties of the orchestration. The fairy tale "Goldilocks and the…

Injury and the orchestral environment: part II. Organisational culture, behavioural norms, and attitudes to injury.

PubMed

Rickert, Dale Ll; Barrett, Margaret S; Ackermann, Bronwen J

2014-06-01

The organisational culture, behavioural norms, and attitudes of a workplace have a profound influence on levels of injury and illness amongst its workers. While this is well established in Work Health and Safety literature, very little research has attempted to understand the influence of organisational culture on injury risk in the orchestral profession. To address this, the current study aimed to investigate the influence of organisational culture on injury outcomes for orchestral musicians. Using a qualitative case study methodology, in-depth semi-structured interviews were undertaken with 10 professional orchestral cellists (2 freelance and 8 fulltime members) from a single Australian orchestra. After initial data analysis, further interviews were undertaken with a set of 5 orchestral management staff as a means of data triangulation. All data were analysed using a themes-based "analysis of narrative" approach. The findings indicate that an orchestral culture exists in which musicians see injury as a sign of weakness, failure, and poor musicianship. Such negative perceptions of injury influence musicians to play through considerable levels of pain and continue performing with injuries. Because of perceived judgment from the orchestral group, musicians were found to conceal injuries from colleagues and management staff. Freelance musicians felt that disclosing injuries may lead to decreased work opportunities, and both full-time and casual musicians felt that "opening up" about injury may subject them to group judgment about their technique or musicianship. The study suggests education measures which may be effective at influencing individual behaviours and attitudes as well as cultural change initiatives which could lead to long-term positive health outcomes in the orchestral workplace.

Optimization of Orchestral Layouts Based on Instrument Directivity Patterns

NASA Astrophysics Data System (ADS)

Stroud, Nathan Paul

The experience of hearing an exceptional symphony orchestra perform in an excel- lent concert hall can be profound and moving, causing a level of excitement not often reached for listeners. Romantic period style orchestral music, recognized for validating the use of intense emotion for aesthetic pleasure, was the last significant development in the history of the orchestra. In an age where orchestral popularity is waning, the possibil- ity of evolving the orchestral sound in our modern era exists through the combination of our current understanding of instrument directivity patterns and their interaction with architectural acoustics. With the aid of wave field synthesis (WFS), newly proposed variations on orchestral layouts are tested virtually using a 64-channel WFS array. Each layout is objectively and subjectively compared for determination of which layout could optimize the sound of the orchestra and revitalize the excitement of the performance.

Enrollment Management: A Market-Centered Perspective

ERIC Educational Resources Information Center

Kalsbeek, David H.; Hossler, Donald

2009-01-01

Enrollment management, the authors suggested in earlier essays, is a deliberate process of achieving an institution's preferred enrollment profile, starting by identifying the strategic purposes and mission of the institution, and then orchestrating the marketing, recruitment, admissions, pricing and aid, retention programs, academic support…

Wargame Pathologies

DTIC Science & Technology

2004-09-01

excluded) do not apply a rigorous and disciplined process of game development , especially in the area of objective definition. Without clear...prior to the game, in controlled circumstances. The actual “game” becomes a discussion of the very orchestrated results of the pre- game “ development ” efforts

Challenge of Supporting Vocational Learning: Empowering Collaboration in a Scripted 3D Game--How Does Teachers' Real-Time Orchestration Make a Difference?

ERIC Educational Resources Information Center

Hamalainen, Raija; Oksanen, Kimmo

2012-01-01

Along with the development of new technologies, orchestrating computer-supported collaborative learning (CSCL) has become a topic of discussion because new learning spaces challenge teacher to support collaborative learning in new ways. However, despite the optimistic notions of teachers' orchestration in CSCL situations, there are still no…

Nature of orchestral noise.

PubMed

O'Brien, Ian; Wilson, Wayne; Bradley, Andrew

2008-08-01

Professional orchestral musicians are at risk of exposure to excessive noise when at work. This is an industry-wide problem that threatens not only the hearing of orchestral musicians but also the way orchestras operate. The research described in this paper recorded noise levels within a professional orchestra over three years in order to provide greater insight to the orchestral noise environment; to guide future research into orchestral noise management and hearing conservation strategies; and to provide a basis for the future education of musicians and their managers. Every rehearsal, performance, and recording from May 2004 to May 2007 was monitored, with the woodwind, brass, and percussion sections monitored in greatest detail. The study recorded dBALEQ and dBC peak data, which are presented in graphical form with accompanying summarized data tables. The findings indicate that the principal trumpet, first and third horns, and principal trombone are at greatest risk of exposure to excessive sustained noise levels and that the percussion and timpani are at greatest risk of exposure to excessive peak noise levels. However, the findings also strongly support the notion that the true nature of orchestral noise is a great deal more complex than this simple statement would imply.

Management of natural crises with choreography and orchestration of federated warning-systems

NASA Astrophysics Data System (ADS)

Haener, Rainer; Waechter, Joachim; Hammitzsch, Martin

2013-04-01

The project Collaborative, Complex and Critical Decision-Support in Evolving Crises (TRIDEC), co-funded by the European Commission in its Seventh Framework Programme focuses on real-time intelligent information management in earth management. The addressed challenges include the design and implementation of a robust and scalable service infrastructure supporting the integration of existing resources, components and systems. Key challenge for TRIDEC is establishing a network of independent systems, cooperatively interacting as a collective in a system-of-systems (SoS). For this purpose TRIDEC adopts enhancements of service-oriented architecture (SOA) principles in terms of an event-driven architecture (EDA) design (SOA 2.0). In this way TRIDEC establishes large-scale concurrent and intelligent information management of a manifold of crisis types by focusing on the integration of autonomous, task-oriented and geographically distributed systems. To this end TRIDEC adapts both ways SOA 2.0 offers: orchestration and choreography. In orchestration, a central knowledge-based processing framework takes control over the involved services and coordinates their execution. Choreography on the other hand avoids central coordination. Rather, each system involved in the SoS follows a global scenario without a single point of control but specifically defined (enacted, agreed upon) trigger conditions. More than orchestration choreography allows collaborative business processes of various heterogeneous sub-systems (e.g. cooperative decision making) by concurrent Complex Event Processing (CEP) and asynchronous communication. These types of interaction adapt the concept of decoupled relationships between information producers (e.g. sensors and sensor systems) and information consumers (e.g. warning systems and warning dissemination systems). Asynchronous communication is useful if a participant wants to trigger specific actions by delegating the responsibility (separation of concerns) for the action to a dedicated participant. Implementing CEP, none of the participants has to know anything about the others. Information is filtered from a stream of manifold events (triggers) assigned to certain and well-defined topics. Both, orchestration and choreography are based on the specification of conversations, which comprise the information model, the roles and responsibilities of all participants, services and business processes, and interaction scenarios. By the maintenance of conversations in commonly available and semantically enabled registries it is possible to establish a federation of systems that is able to provide dynamic, yet coherent behaviour. TRIDEC establishes a reliable and adaptive SoS (concurrent processing of events and activities) which exposes emergent behaviour (e.g. intelligent and adaptive monitoring strategies, cooperative decision making or dynamic system configuration) even in case of partly system failures. In a process of self-organising (task balancing and dynamic delegation of responsibilities) as SoS is able to secure the reliability and responsiveness for real-time, long running & durable monitoring activities. Concepts like Design by Contract (DbC), service level agreements (SLA), redundancy- and failover-strategies as well as a comprehensive knowledge-based description of all facets of all potential interactions ensure the interoperability, robustness and expected behaviour of the TRIDEC SoS even if it is composed of managerial independent sub-systems. Beyond these features, the adaptability of a SoS offers scalability and virtualization regarding both, systems and domains. Composability and re-use of functionality can be achieved easily even across domain-boundaries.

DISTINGUISHING BETWEEN FERTILIZATION FAILURE AND EARLY PREGNANCY LOSS WHEN IDENTIFYING MALE-MEDIATED ADVERSE PREGNANCY OUTCOMES

EPA Science Inventory

Successful reproduction depends upon the precise orchestration of many physiological processes. With respect to male reproductive performance, normal copulatory behavior and ejaculatory function are required to insure that semen is deposited in the female tract. Then, a suffici...

Orchestrating cytoskeleton and intracellular vesicle traffic to build functional immunological synapses.

PubMed

Soares, Helena; Lasserre, Rémi; Alcover, Andrés

2013-11-01

Immunological synapses are specialized cell-cell contacts formed between T lymphocytes and antigen-presenting cells. They are induced upon antigen recognition and are crucial for T-cell activation and effector functions. The generation and function of immunological synapses depend on an active T-cell polarization process, which results from a finely orchestrated crosstalk between the antigen receptor signal transduction machinery, the actin and microtubule cytoskeletons, and controlled vesicle traffic. Although we understand how some of these particular events are regulated, we still lack knowledge on how these multiple cellular elements are harmonized to ensure appropriate T-cell responses. We discuss here our view on how T-cell receptor signal transduction initially commands cytoskeletal and vesicle traffic polarization, which in turn sets the immunological synapse molecular design that regulates T-cell activation. We also discuss how the human immunodeficiency virus (HIV-1) hijacks some of these processes impairing immunological synapse generation and function. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Implementing High-Performance Geometric Multigrid Solver with Naturally Grained Messages

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

Shan, Hongzhang; Williams, Samuel; Zheng, Yili

2015-10-26

Structured-grid linear solvers often require manually packing and unpacking of communication data to achieve high performance.Orchestrating this process efficiently is challenging, labor-intensive, and potentially error-prone.In this paper, we explore an alternative approach that communicates the data with naturally grained messagesizes without manual packing and unpacking. This approach is the distributed analogue of shared-memory programming, taking advantage of the global addressspace in PGAS languages to provide substantial programming ease. However, its performance may suffer from the large number of small messages. We investigate theruntime support required in the UPC ++ library for this naturally grained version to close the performance gapmore » between the two approaches and attain comparable performance at scale using the High-Performance Geometric Multgrid (HPGMG-FV) benchmark as a driver.« less

Orchestrating care: nursing practice with hospitalised older adults.

PubMed

Dahlke, Sherry Ann; Phinney, Alison; Hall, Wendy Ann; Rodney, Patricia; Baumbusch, Jennifer

2015-12-01

The increased incidence of health challenges with aging means that nurses are increasingly caring for older adults, often in hospital settings. Research about the complexity of nursing practice with this population remains limited. To seek an explanation of nursing practice with hospitalised older adults. Design. A grounded theory study guided by symbolic interactionism was used to explore nursing practice with hospitalised older adults from a nursing perspective. Glaserian grounded theory methods were used to develop a mid-range theory after analysis of 375 hours of participant observation, 35 interviews with 24 participants and review of selected documents. The theory of orchestrating care was developed to explain how nurses are continuously trying to manage their work environments by understanding the status of the patients, their unit, mobilising the assistance of others and stretching available resources to resolve their problem of providing their older patients with what they perceived as 'good care' while sustaining themselves as 'good' nurses. They described their practice environments as hard and under-resourced. Orchestrating care is comprised of two subprocesses: building synergy and minimising strain. These two processes both facilitated and constrained each other and nurses' abilities to orchestrate care. Although system issues presented serious constraints to nursing practice, the ways in which nurses were making meaning of their work environment both aided them in managing their challenges and constrained their agency. Nurses need to be encouraged to share their important perspective about older adult care. Administrators have a role to play in giving nurses voice in workplace committees and in forums. Further research is needed to better understand how multidisciplinary teams influence care of hospitalized older adults. © 2014 John Wiley & Sons Ltd.

School Violence and Theoretically Atypical Schools: The Principal's Centrality in Orchestrating Safe Schools

ERIC Educational Resources Information Center

Astor, Ron Avi; Benbenishty, Rami; Estrada, Jose Nunez

2009-01-01

Theories often assume that schools in communities with high violence also have high rates of school violence, yet there are schools with very low violence in high violence communities. Organizational variables within these schools may buffer community influences. Nine "atypical" schools are selected from a national database in Israel.…

DCASR (Defense Contract Administration Services Region) Boston, Strategic/Total Quality Management Master Plan Using Management by Planning (MBP)

DTIC Science & Technology

1989-06-01

employees. A policy consists of targets, plans, and target values. Policy Deployment: One English translation for hoshin kanri . (Others are management by...policy and hoshin planning.) Policy deployment orchestrates continuous improvement in a way that fosters individual initiative and alignment. Process

A general catalytic β-C-H carbonylation of aliphatic amines to β-lactams.

PubMed

Willcox, Darren; Chappell, Ben G N; Hogg, Kirsten F; Calleja, Jonas; Smalley, Adam P; Gaunt, Matthew J

2016-11-18

Methods for the synthesis and functionalization of amines are intrinsically important to a variety of chemical applications. We present a general carbon-hydrogen bond activation process that combines readily available aliphatic amines and the feedstock gas carbon monoxide to form synthetically versatile value-added amide products. The operationally straightforward palladium-catalyzed process exploits a distinct reaction pathway, wherein a sterically hindered carboxylate ligand orchestrates an amine attack on a palladium anhydride to transform aliphatic amines into β-lactams. The reaction is successful with a wide range of secondary amines and can be used as a late-stage functionalization tactic to deliver advanced, highly functionalized amine products of utility for pharmaceutical research and other areas. Copyright © 2016, American Association for the Advancement of Science.

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.

Workflows for Full Waveform Inversions

NASA Astrophysics Data System (ADS)

Boehm, Christian; Krischer, Lion; Afanasiev, Michael; van Driel, Martin; May, Dave A.; Rietmann, Max; Fichtner, Andreas

2017-04-01

Despite many theoretical advances and the increasing availability of high-performance computing clusters, full seismic waveform inversions still face considerable challenges regarding data and workflow management. While the community has access to solvers which can harness modern heterogeneous computing architectures, the computational bottleneck has fallen to these often manpower-bounded issues that need to be overcome to facilitate further progress. Modern inversions involve huge amounts of data and require a tight integration between numerical PDE solvers, data acquisition and processing systems, nonlinear optimization libraries, and job orchestration frameworks. To this end we created a set of libraries and applications revolving around Salvus (http://salvus.io), a novel software package designed to solve large-scale full waveform inverse problems. This presentation focuses on solving passive source seismic full waveform inversions from local to global scales with Salvus. We discuss (i) design choices for the aforementioned components required for full waveform modeling and inversion, (ii) their implementation in the Salvus framework, and (iii) how it is all tied together by a usable workflow system. We combine state-of-the-art algorithms ranging from high-order finite-element solutions of the wave equation to quasi-Newton optimization algorithms using trust-region methods that can handle inexact derivatives. All is steered by an automated interactive graph-based workflow framework capable of orchestrating all necessary pieces. This naturally facilitates the creation of new Earth models and hopefully sparks new scientific insights. Additionally, and even more importantly, it enhances reproducibility and reliability of the final results.

Toward an E-Government Semantic Platform

NASA Astrophysics Data System (ADS)

Sbodio, Marco Luca; Moulin, Claude; Benamou, Norbert; Barthès, Jean-Paul

This chapter describes the major aspects of an e-government platform in which semantics underpins more traditional technologies in order to enable new capabilities and to overcome technical and cultural challenges. The design and development of such an e-government Semantic Platform has been conducted with the financial support of the European Commission through the Terregov research project: "Impact of e-government on Territorial Government Services" (Terregov 2008). The goal of this platform is to let local government and government agencies offer online access to their services in an interoperable way, and to allow them to participate in orchestrated processes involving services provided by multiple agencies. Implementing a business process through an electronic procedure is indeed a core goal in any networked organization. However, the field of e-government brings specific constraints to the operations allowed in procedures, especially concerning the flow of private citizens' data: because of legal reasons in most countries, such data are allowed to circulate only from agency to agency directly. In order to promote transparency and responsibility in e-government while respecting the specific constraints on data flows, Terregov supports the creation of centrally controlled orchestrated processes; while the cross agencies data flows are centrally managed, data flow directly across agencies.

Emerging Imaging and Genomic Tools for Developmental Systems Biology.

PubMed

Liu, Zhe; Keller, Philipp J

2016-03-21

Animal development is a complex and dynamic process orchestrated by exquisitely timed cell lineage commitment, divisions, migration, and morphological changes at the single-cell level. In the past decade, extensive genetic, stem cell, and genomic studies provided crucial insights into molecular underpinnings and the functional importance of genetic pathways governing various cellular differentiation processes. However, it is still largely unknown how the precise coordination of these pathways is achieved at the whole-organism level and how the highly regulated spatiotemporal choreography of development is established in turn. Here, we discuss the latest technological advances in imaging and single-cell genomics that hold great promise for advancing our understanding of this intricate process. We propose an integrated approach that combines such methods to quantitatively decipher in vivo cellular dynamic behaviors and their underlying molecular mechanisms at the systems level with single-cell, single-molecule resolution. Copyright © 2016 Elsevier Inc. All rights reserved.

Consciousness in the universe: a review of the 'Orch OR' theory.

PubMed

Hameroff, Stuart; Penrose, Roger

2014-03-01

The nature of consciousness, the mechanism by which it occurs in the brain, and its ultimate place in the universe are unknown. We proposed in the mid 1990's that consciousness depends on biologically 'orchestrated' coherent quantum processes in collections of microtubules within brain neurons, that these quantum processes correlate with, and regulate, neuronal synaptic and membrane activity, and that the continuous Schrödinger evolution of each such process terminates in accordance with the specific Diósi-Penrose (DP) scheme of 'objective reduction' ('OR') of the quantum state. This orchestrated OR activity ('Orch OR') is taken to result in moments of conscious awareness and/or choice. The DP form of OR is related to the fundamentals of quantum mechanics and space-time geometry, so Orch OR suggests that there is a connection between the brain's biomolecular processes and the basic structure of the universe. Here we review Orch OR in light of criticisms and developments in quantum biology, neuroscience, physics and cosmology. We also introduce a novel suggestion of 'beat frequencies' of faster microtubule vibrations as a possible source of the observed electro-encephalographic ('EEG') correlates of consciousness. We conclude that consciousness plays an intrinsic role in the universe. Copyright © 2013 Elsevier B.V. All rights reserved.

Organizational Implications of the U.S. Army’s Increasing Demand for Explosive Ordnance Disposal Capabilities

DTIC Science & Technology

2008-05-22

Washington D.C: Government Printing Office, 1976), 1-1 to 1-5. 43 Ibid, 2-1 to 2-32. 16 “orchestrated ballet of farm implements.”44 The Army’s...Orchestrated Ballet of Farm Implements”, Engineer Bulletin, August 1996, http://fas.org/man/dod 101/sys/land/docs /960800-greene2.htm (accessed 5 April...An Alternative to the Orchestrated Ballet of Farm Implements” Engineer Bulletin (August 1996), http://fas.org/man/dod_101/sys/land/docs/960800

Decentralized operating procedures for orchestrating data and behavior across distributed military systems and assets

NASA Astrophysics Data System (ADS)

Peach, Nicholas

2011-06-01

In this paper, we present a method for a highly decentralized yet structured and flexible approach to achieve systems interoperability by orchestrating data and behavior across distributed military systems and assets with security considerations addressed from the beginning. We describe an architecture of a tool-based design of business processes called Decentralized Operating Procedures (DOP) and the deployment of DOPs onto run time nodes, supporting the parallel execution of each DOP at multiple implementation nodes (fixed locations, vehicles, sensors and soldiers) throughout a battlefield to achieve flexible and reliable interoperability. The described method allows the architecture to; a) provide fine grain control of the collection and delivery of data between systems; b) allow the definition of a DOP at a strategic (or doctrine) level by defining required system behavior through process syntax at an abstract level, agnostic of implementation details; c) deploy a DOP into heterogeneous environments by the nomination of actual system interfaces and roles at a tactical level; d) rapidly deploy new DOPs in support of new tactics and systems; e) support multiple instances of a DOP in support of multiple missions; f) dynamically add or remove run-time nodes from a specific DOP instance as missions requirements change; g) model the passage of, and business reasons for the transmission of each data message to a specific DOP instance to support accreditation; h) run on low powered computers with lightweight tactical messaging. This approach is designed to extend the capabilities of existing standards, such as the Generic Vehicle Architecture (GVA).

Molecular mechanisms involved in the early steps of flavivirus cell entry.

PubMed

Kaufmann, Bärbel; Rossmann, Michael G

2011-01-01

Flaviviruses enter their host cells by receptor-mediated endocytosis, a well-orchestrated process of receptor recognition, penetration and uncoating. Recent findings on these early steps in the life cycle of flaviviruses are the focus of this review. Copyright © 2010 Institut Pasteur. Published by Elsevier SAS. All rights reserved.

Application of Online Discussion and Cooperative Learning Strategies to Online and Blended College Courses

ERIC Educational Resources Information Center

Lynch, Douglas J.

2010-01-01

Effective online instructional practices may be applied to online and blended college courses. Carefully orchestrated online discussions support learning well beyond the limited face-to-face course time. Students gain greater depth of academic understanding and leadership skills if cooperative learning groups use research-based process and…

Making Wishes Come True: A Guide to Successful School Expansions.

ERIC Educational Resources Information Center

Fowle, Bruce

1993-01-01

A school expansion project should be carefully orchestrated with following steps: compiling list of everyone's perceived needs; determining what is affordable; developing program of requirements; developing a master plan; and overseeing the process. Case studies of two New York State schools (one urban and one suburban) illustrate how the location…

The Anaphase Promoting Complex Is Required for Memory Function in Mice

ERIC Educational Resources Information Center

Kuczera, Tanja; Stilling, Roman Manuel; Hsia, Hung-En; Bahari-Javan, Sanaz; Irniger, Stefan; Nasmyth, Kim; Sananbenesi, Farahnaz; Fischer, Andre

2011-01-01

Learning and memory processes critically involve the orchestrated regulation of de novo protein synthesis. On the other hand it has become clear that regulated protein degradation also plays a major role in neuronal plasticity and learning behavior. One of the key pathways mediating protein degradation is proteosomal protein destruction. The…

Wound healing revised: A novel reepithelialization mechanism revealed by in vitro and in silico models

PubMed Central

Safferling, Kai; Sütterlin, Thomas; Westphal, Kathi; Ernst, Claudia; Breuhahn, Kai; James, Merlin; Jäger, Dirk; Halama, Niels

2013-01-01

Wound healing is a complex process in which a tissue’s individual cells have to be orchestrated in an efficient and robust way. We integrated multiplex protein analysis, immunohistochemical analysis, and whole-slide imaging into a novel medium-throughput platform for quantitatively capturing proliferation, differentiation, and migration in large numbers of organotypic skin cultures comprising epidermis and dermis. Using fluorescent time-lag staining, we were able to infer source and final destination of keratinocytes in the healing epidermis. This resulted in a novel extending shield reepithelialization mechanism, which we confirmed by computational multicellular modeling and perturbation of tongue extension. This work provides a consistent experimental and theoretical model for epidermal wound closure in 3D, negating the previously proposed concepts of epidermal tongue extension and highlighting the so far underestimated role of the surrounding tissue. Based on our findings, epidermal wound closure is a process in which cell behavior is orchestrated by a higher level of tissue control that 2D monolayer assays are not able to capture. PMID:24385489

Using container orchestration to improve service management at the RAL Tier-1

NASA Astrophysics Data System (ADS)

Lahiff, Andrew; Collier, Ian

2017-10-01

In recent years container orchestration has been emerging as a means of gaining many potential benefits compared to a traditional static infrastructure, such as increased utilisation through multi-tenancy, improved availability due to self-healing, and the ability to handle changing loads due to elasticity and auto-scaling. To this end we have been investigating migrating services at the RAL Tier-1 to an Apache Mesos cluster. In this model the concept of individual machines is abstracted away and services are run in containers on a cluster of machines, managed by schedulers, enabling a high degree of automation. Here we describe Mesos, the infrastructure deployed at RAL, and describe in detail the explicit example of running a batch farm on Mesos.

THE RHIC SEQUENCER.

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

VAN ZEIJTS,J.; DOTTAVIO,T.; FRAK,B.

The Relativistic Heavy Ion Collider (RHIC) has a high level asynchronous time-line driven by a controlling program called the ''Sequencer''. Most high-level magnet and beam related issues are orchestrated by this system. The system also plays an important task in coordinated data acquisition and saving. We present the program, operator interface, operational impact and experience.

The Clostridium sporulation programs: diversity and preservation of endospore differentiation.

PubMed

Al-Hinai, Mohab A; Jones, Shawn W; Papoutsakis, Eleftherios T

2015-03-01

Bacillus and Clostridium organisms initiate the sporulation process when unfavorable conditions are detected. The sporulation process is a carefully orchestrated cascade of events at both the transcriptional and posttranslational levels involving a multitude of sigma factors, transcription factors, proteases, and phosphatases. Like Bacillus genomes, sequenced Clostridium genomes contain genes for all major sporulation-specific transcription and sigma factors (spo0A, sigH, sigF, sigE, sigG, and sigK) that orchestrate the sporulation program. However, recent studies have shown that there are substantial differences in the sporulation programs between the two genera as well as among different Clostridium species. First, in the absence of a Bacillus-like phosphorelay system, activation of Spo0A in Clostridium organisms is carried out by a number of orphan histidine kinases. Second, downstream of Spo0A, the transcriptional and posttranslational regulation of the canonical set of four sporulation-specific sigma factors (σ(F), σ(E), σ(G), and σ(K)) display different patterns, not only compared to Bacillus but also among Clostridium organisms. Finally, recent studies demonstrated that σ(K), the last sigma factor to be activated according to the Bacillus subtilis model, is involved in the very early stages of sporulation in Clostridium acetobutylicum, C. perfringens, and C. botulinum as well as in the very late stages of spore maturation in C. acetobutylicum. Despite profound differences in initiation, propagation, and orchestration of expression of spore morphogenetic components, these findings demonstrate not only the robustness of the endospore sporulation program but also the plasticity of the program to generate different complex phenotypes, some apparently regulated at the epigenetic level. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The Clostridium Sporulation Programs: Diversity and Preservation of Endospore Differentiation

PubMed Central

Al-Hinai, Mohab A.; Jones, Shawn W.

2015-01-01

SUMMARY Bacillus and Clostridium organisms initiate the sporulation process when unfavorable conditions are detected. The sporulation process is a carefully orchestrated cascade of events at both the transcriptional and posttranslational levels involving a multitude of sigma factors, transcription factors, proteases, and phosphatases. Like Bacillus genomes, sequenced Clostridium genomes contain genes for all major sporulation-specific transcription and sigma factors (spo0A, sigH, sigF, sigE, sigG, and sigK) that orchestrate the sporulation program. However, recent studies have shown that there are substantial differences in the sporulation programs between the two genera as well as among different Clostridium species. First, in the absence of a Bacillus-like phosphorelay system, activation of Spo0A in Clostridium organisms is carried out by a number of orphan histidine kinases. Second, downstream of Spo0A, the transcriptional and posttranslational regulation of the canonical set of four sporulation-specific sigma factors (σF, σE, σG, and σK) display different patterns, not only compared to Bacillus but also among Clostridium organisms. Finally, recent studies demonstrated that σK, the last sigma factor to be activated according to the Bacillus subtilis model, is involved in the very early stages of sporulation in Clostridium acetobutylicum, C. perfringens, and C. botulinum as well as in the very late stages of spore maturation in C. acetobutylicum. Despite profound differences in initiation, propagation, and orchestration of expression of spore morphogenetic components, these findings demonstrate not only the robustness of the endospore sporulation program but also the plasticity of the program to generate different complex phenotypes, some apparently regulated at the epigenetic level. PMID:25631287

The Clostridium Sporulation Programs: Diversity and Preservation of Endospore Differentiation

DOE PAGES

Al-Hinai, Mohab A.; Jones, Shawn W.; Papoutsakis, Eleftherios T.

2015-01-28

Bacillus and Clostridium organisms initiate the sporulation process when unfavorable conditions are detected. The sporulation process is a carefully orchestrated cascade of events at both the transcriptional and posttranslational levels involving a multitude of sigma factors, transcription factors, proteases, and phosphatases. Like Bacillus genomes, sequenced Clostridium genomes contain genes for all major sporulation-specific transcription and sigma factors (spo0A, sigH, sigF, sigE, sigG, and sigK) that orchestrate the sporulation program. However, recent studies have shown that there are substantial differences in the sporulation programs between the two genera as well as among different Clostridium species. First, in the absence of amore » Bacillus-like phosphorelay system, activation of Spo0A in Clostridium organisms is carried out by a number of orphan histidine kinases. Second, downstream of Spo0A, the transcriptional and posttranslational regulation of the canonical set of four sporulation-specific sigma factors (σF, σE, σG, and σK) display different patterns, not only compared to Bacillus but also among Clostridium organisms. Finally, recent studies demonstrated that σK, the last sigma factor to be activated according to the Bacillus subtilis model, is involved in the very early stages of sporulation in Clostridium acetobutylicum, C. perfringens, and C. botulinum as well as in the very late stages of spore maturation in C. acetobutylicum. Despite profound differences in initiation, propagation, and orchestration of expression of spore morphogenetic components, these findings demonstrate not only the robustness of the endospore sporulation program but also the plasticity of the program to generate different complex phenotypes, some apparently regulated at the epigenetic level.« less

FAST: A fully asynchronous and status-tracking pattern for geoprocessing services orchestration

NASA Astrophysics Data System (ADS)

Wu, Huayi; You, Lan; Gui, Zhipeng; Gao, Shuang; Li, Zhenqiang; Yu, Jingmin

2014-09-01

Geoprocessing service orchestration (GSO) provides a unified and flexible way to implement cross-application, long-lived, and multi-step geoprocessing service workflows by coordinating geoprocessing services collaboratively. Usually, geoprocessing services and geoprocessing service workflows are data and/or computing intensive. The intensity feature may make the execution process of a workflow time-consuming. Since it initials an execution request without blocking other interactions on the client side, an asynchronous mechanism is especially appropriate for GSO workflows. Many critical problems remain to be solved in existing asynchronous patterns for GSO including difficulties in improving performance, status tracking, and clarifying the workflow structure. These problems are a challenge when orchestrating performance efficiency, making statuses instantly available, and constructing clearly structured GSO workflows. A Fully Asynchronous and Status-Tracking (FAST) pattern that adopts asynchronous interactions throughout the whole communication tier of a workflow is proposed for GSO. The proposed FAST pattern includes a mechanism that actively pushes the latest status to clients instantly and economically. An independent proxy was designed to isolate the status tracking logic from the geoprocessing business logic, which assists the formation of a clear GSO workflow structure. A workflow was implemented in the FAST pattern to simulate the flooding process in the Poyang Lake region. Experimental results show that the proposed FAST pattern can efficiently tackle data/computing intensive geoprocessing tasks. The performance of all collaborative partners was improved due to the asynchronous mechanism throughout communication tier. A status-tracking mechanism helps users retrieve the latest running status of a GSO workflow in an efficient and instant way. The clear structure of the GSO workflow lowers the barriers for geospatial domain experts and model designers to compose asynchronous GSO workflows. Most importantly, it provides better support for locating and diagnosing potential exceptions.

Orchestration of carbohydrate processing for crassulacean acid metabolism

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

Borland, Anne M.; Guo, Hao-Bo; Yang, Xiaohan

The production of phosphoenolpyruvate as a substrate for nocturnal CO 2 uptake represents a significant sink for carbohydrate in CAM plants which has to be balanced with the provisioning of carbohydrate for growth and maintenance. In starch-storing CAM species, diversification in chloroplast metabolite transporters, and the deployment of both phosphorolytic and hydrolytic routes of starch degradation accommodate a division of labour in directing C-skeletons towards nocturnal carboxylation or production of sucrose for growth. In soluble-sugar storing CAM plants, the vacuole plays a central role in managing carbon homeostasis. The molecular identities of various types of vacuolar sugar transporters have onlymore » been identified for C 3 species within the last 10 years. In conclusion, the recent availability of CAM genomes enables the identification of putative orthologues of vacuolar sugar transporters which represent strategic targets for orchestrating the diel provisioning of substrate for nocturnal carboxylation and growth.« less

Cascade of neural processing orchestrates cognitive control in human frontal cortex

PubMed Central

Tang, Hanlin; Yu, Hsiang-Yu; Chou, Chien-Chen; Crone, Nathan E; Madsen, Joseph R; Anderson, William S; Kreiman, Gabriel

2016-01-01

Rapid and flexible interpretation of conflicting sensory inputs in the context of current goals is a critical component of cognitive control that is orchestrated by frontal cortex. The relative roles of distinct subregions within frontal cortex are poorly understood. To examine the dynamics underlying cognitive control across frontal regions, we took advantage of the spatiotemporal resolution of intracranial recordings in epilepsy patients while subjects resolved color-word conflict. We observed differential activity preceding the behavioral responses to conflict trials throughout frontal cortex; this activity was correlated with behavioral reaction times. These signals emerged first in anterior cingulate cortex (ACC) before dorsolateral prefrontal cortex (dlPFC), followed by medial frontal cortex (mFC) and then by orbitofrontal cortex (OFC). These results disassociate the frontal subregions based on their dynamics, and suggest a temporal hierarchy for cognitive control in human cortex. DOI: http://dx.doi.org/10.7554/eLife.12352.001 PMID:26888070

Roles of Teachers in Orchestrating Learning in Elementary Science Classrooms

NASA Astrophysics Data System (ADS)

Zhai, Junqing; Tan, Aik-Ling

2015-12-01

This study delves into the different roles that elementary science teachers play in the classroom to orchestrate science learning opportunities for students. Examining the classroom practices of three elementary science teachers in Singapore, we found that teachers shuttle between four key roles in enabling student learning in science. Teachers can play the role of (1) dispenser of knowledge (giver), (2) mentor of learning (advisor), (3) monitor of students' activities (police), and (4) partner in inquiry (colearner). These roles are dynamic, and while teachers show a preference for one of the four roles, factors such as the nature of the task, the types of students, as well as the availability of time and resources affect the role that teachers adopt. The roles that teachers play in the classroom have implications for the practice of science as inquiry in the classroom as well as the identities that teachers and students form in the science learning process.

Orchestration of carbohydrate processing for crassulacean acid metabolism

DOE PAGES

Borland, Anne M.; Guo, Hao-Bo; Yang, Xiaohan; ...

2016-04-19

The production of phosphoenolpyruvate as a substrate for nocturnal CO 2 uptake represents a significant sink for carbohydrate in CAM plants which has to be balanced with the provisioning of carbohydrate for growth and maintenance. In starch-storing CAM species, diversification in chloroplast metabolite transporters, and the deployment of both phosphorolytic and hydrolytic routes of starch degradation accommodate a division of labour in directing C-skeletons towards nocturnal carboxylation or production of sucrose for growth. In soluble-sugar storing CAM plants, the vacuole plays a central role in managing carbon homeostasis. The molecular identities of various types of vacuolar sugar transporters have onlymore » been identified for C 3 species within the last 10 years. In conclusion, the recent availability of CAM genomes enables the identification of putative orthologues of vacuolar sugar transporters which represent strategic targets for orchestrating the diel provisioning of substrate for nocturnal carboxylation and growth.« less

aPKCλ/ι and aPKCζ Contribute to Podocyte Differentiation and Glomerular Maturation

PubMed Central

Hartleben, Björn; Widmeier, Eugen; Suhm, Martina; Worthmann, Kirstin; Schell, Christoph; Helmstädter, Martin; Wiech, Thorsten; Walz, Gerd; Leitges, Michael; Schiffer, Mario

2013-01-01

Precise positioning of the highly complex interdigitating podocyte foot processes is critical to form the normal glomerular filtration barrier, but the molecular programs driving this process are unknown. The protein atypical protein kinase C (aPKC)—a component of the Par complex, which localizes to tight junctions and interacts with slit diaphragm proteins—may play a role. Here, we found that the combined deletion of the aPKCλ/ι and aPKCζ isoforms in podocytes associated with incorrectly positioned centrosomes and Golgi apparatus and mislocalized molecules of the slit diaphragm. Furthermore, aPKC-deficient podocytes failed to form the normal network of foot processes, leading to defective glomerular maturation with incomplete capillary formation and mesangiolysis. Our results suggest that aPKC isoforms orchestrate the formation of the podocyte processes essential for normal glomerular development and kidney function. Defective aPKC signaling results in a dramatically simplified glomerular architecture, causing severe proteinuria and perinatal death. PMID:23334392

Interplay between Clinical Guidelines and Organizational Workflow Systems. Experience from the MobiGuide Project.

PubMed

Shabo, Amnon; Peleg, Mor; Parimbelli, Enea; Quaglini, Silvana; Napolitano, Carlo

2016-12-07

Implementing a decision-support system within a healthcare organization requires integration of clinical domain knowledge with resource constraints. Computer-interpretable guidelines (CIG) are excellent instruments for addressing clinical aspects while business process management (BPM) languages and Workflow (Wf) engines manage the logistic organizational constraints. Our objective is the orchestration of all the relevant factors needed for a successful execution of patient's care pathways, especially when spanning the continuum of care, from acute to community or home care. We considered three strategies for integrating CIGs with organizational workflows: extending the CIG or BPM languages and their engines, or creating an interplay between them. We used the interplay approach to implement a set of use cases arising from a CIG implementation in the domain of Atrial Fibrillation. To provide a more scalable and standards-based solution, we explored the use of Cross-Enterprise Document Workflow Integration Profile. We describe our proof-of-concept implementation of five use cases. We utilized the Personal Health Record of the MobiGuide project to implement a loosely-coupled approach between the Activiti BPM engine and the Picard CIG engine. Changes in the PHR were detected by polling. IHE profiles were used to develop workflow documents that orchestrate cross-enterprise execution of cardioversion. Interplay between CIG and BPM engines can support orchestration of care flows within organizational settings.

Enhanced intelligence through optimized TCPED concepts for airborne ISR

NASA Astrophysics Data System (ADS)

Spitzer, M.; Kappes, E.; Böker, D.

2012-06-01

Current multinational operations show an increased demand for high quality actionable intelligence for different operational levels and users. In order to achieve sufficient availability, quality and reliability of information, various ISR assets are orchestrated within operational theatres. Especially airborne Intelligence, Surveillance and Reconnaissance (ISR) assets provide - due to their endurance, non-intrusiveness, robustness, wide spectrum of sensors and flexibility to mission changes - significant intelligence coverage of areas of interest. An efficient and balanced utilization of airborne ISR assets calls for advanced concepts for the entire ISR process framework including the Tasking, Collection, Processing, Exploitation and Dissemination (TCPED). Beyond this, the employment of current visualization concepts, shared information bases and information customer profiles, as well as an adequate combination of ISR sensors with different information age and dynamic (online) retasking process elements provides the optimization of interlinked TCPED processes towards higher process robustness, shorter process duration, more flexibility between ISR missions and, finally, adequate "entry points" for information requirements by operational users and commands. In addition, relevant Trade-offs of distributed and dynamic TCPED processes are examined and future trends are depicted.

Abstracting application deployment on Cloud infrastructures

NASA Astrophysics Data System (ADS)

Aiftimiei, D. C.; Fattibene, E.; Gargana, R.; Panella, M.; Salomoni, D.

2017-10-01

Deploying a complex application on a Cloud-based infrastructure can be a challenging task. In this contribution we present an approach for Cloud-based deployment of applications and its present or future implementation in the framework of several projects, such as “!CHAOS: a cloud of controls” [1], a project funded by MIUR (Italian Ministry of Research and Education) to create a Cloud-based deployment of a control system and data acquisition framework, “INDIGO-DataCloud” [2], an EC H2020 project targeting among other things high-level deployment of applications on hybrid Clouds, and “Open City Platform”[3], an Italian project aiming to provide open Cloud solutions for Italian Public Administrations. We considered to use an orchestration service to hide the complex deployment of the application components, and to build an abstraction layer on top of the orchestration one. Through Heat [4] orchestration service, we prototyped a dynamic, on-demand, scalable platform of software components, based on OpenStack infrastructures. On top of the orchestration service we developed a prototype of a web interface exploiting the Heat APIs. The user can start an instance of the application without having knowledge about the underlying Cloud infrastructure and services. Moreover, the platform instance can be customized by choosing parameters related to the application such as the size of a File System or the number of instances of a NoSQL DB cluster. As soon as the desired platform is running, the web interface offers the possibility to scale some infrastructure components. In this contribution we describe the solution design and implementation, based on the application requirements, the details of the development of both the Heat templates and of the web interface, together with possible exploitation strategies of this work in Cloud data centers.

Feeling Present in Arousing Virtual Reality Worlds: Prefrontal Brain Regions Differentially Orchestrate Presence Experience in Adults and Children

PubMed Central

Baumgartner, Thomas; Speck, Dominique; Wettstein, Denise; Masnari, Ornella; Beeli, Gian; Jäncke, Lutz

2008-01-01

Virtual reality (VR) is a powerful tool for simulating aspects of the real world. The success of VR is thought to depend on its ability to evoke a sense of “being there”, that is, the feeling of “Presence”. In view of the rapid progress in the development of increasingly more sophisticated virtual environments (VE), the importance of understanding the neural underpinnings of presence is growing. To date however, the neural correlates of this phenomenon have received very scant attention. An fMRI-based study with 52 adults and 25 children was therefore conducted using a highly immersive VE. The experience of presence in adult subjects was found to be modulated by two major strategies involving two homologous prefrontal brain structures. Whereas the right DLPFC controlled the sense of presence by down-regulating the activation in the egocentric dorsal visual processing stream, the left DLPFC up-regulated widespread areas of the medial prefrontal cortex known to be involved in self-reflective and stimulus-independent thoughts. In contrast, there was no evidence of these two strategies in children. In fact, anatomical analyses showed that these two prefrontal areas have not yet reached full maturity in children. Taken together, this study presents the first findings that show activation of a highly specific neural network orchestrating the experience of presence in adult subjects, and that the absence of activity in this neural network might contribute to the generally increased susceptibility of children for the experience of presence in VEs. PMID:18958209

Crystal Clear Assessment

ERIC Educational Resources Information Center

Stone, Jody H.; Lockhart, Amy

2013-01-01

Great science activities don't just happen; they are orchestrated by highly skilled teachers who are creative, caring, and innovative. Effective classroom teachers possess a deep understanding of the developmental characteristics of their students and are adept at translating this understanding into opportunities for individual students to…

Mechanical regulation of cardiac development

PubMed Central

Lindsey, Stephanie E.; Butcher, Jonathan T.; Yalcin, Huseyin C.

2014-01-01

Mechanical forces are essential contributors to and unavoidable components of cardiac formation, both inducing and orchestrating local and global molecular and cellular changes. Experimental animal studies have contributed substantially to understanding the mechanobiology of heart development. More recent integration of high-resolution imaging modalities with computational modeling has greatly improved our quantitative understanding of hemodynamic flow in heart development. Merging these latest experimental technologies with molecular and genetic signaling analysis will accelerate our understanding of the relationships integrating mechanical and biological signaling for proper cardiac formation. These advances will likely be essential for clinically translatable guidance for targeted interventions to rescue malforming hearts and/or reconfigure malformed circulations for optimal performance. This review summarizes our current understanding on the levels of mechanical signaling in the heart and their roles in orchestrating cardiac development. PMID:25191277

Concise Review: Stem Cells in Osteoimmunology.

PubMed

Fierro, Fernando A; Nolta, Jan A; Adamopoulos, Iannis E

2017-06-01

Bone remodeling is a lifelong process in which mature bone tissue is removed from the skeleton by bone resorption and is replenished by new during ossification or bone formation. The remodeling cycle requires both the differentiation and activation of two cell types with opposing functions; the osteoclast, which orchestrates bone resorption, and the osteoblast, which orchestrates bone formation. The differentiation of these cells from their respective precursors is a process which has been overshadowed by enigma, particularly because the precise osteoclast precursor has not been identified and because the identification of skeletal stem cells, which give rise to osteoblasts, is very recent. Latest advances in the area of stem cell biology have enabled us to gain a better understanding of how these differentiation processes occur in physiological and pathological conditions. In this review we postulate that modulation of stem cells during inflammatory conditions is a necessary prerequisite of bone remodeling and therefore an essential new component to the field of osteoimmunology. In this context, we highlight the role of transcription factor nuclear factor of activated T cells cytoplasmic 1 (NFATc1), because it directly links inflammation with differentiation of osteoclasts and osteoblasts. Stem Cells 2017;35:1461-1467. © 2017 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Implications of Metaphors in Defining Technical Communication.

ERIC Educational Resources Information Center

Beck, Charles E.

1991-01-01

Identifies four metaphors that appear dominant in current studies in the field of technical communication: transmitter, channel, balance, and bridge. Suggests limitations upon each of the metaphors. Discusses the alternative metaphors of lock, translator, transformer, synthesizer, conductor, and orchestrator. Proposes orchestration as a fruitful…

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

PubMed

Galluzzi, Lorenzo; Vitale, Ilio; Aaronson, Stuart A; Abrams, John M; Adam, Dieter; Agostinis, Patrizia; Alnemri, Emad S; Altucci, Lucia; Amelio, Ivano; Andrews, David W; Annicchiarico-Petruzzelli, Margherita; Antonov, Alexey V; Arama, Eli; Baehrecke, Eric H; Barlev, Nickolai A; Bazan, Nicolas G; Bernassola, Francesca; Bertrand, Mathieu J M; Bianchi, Katiuscia; Blagosklonny, Mikhail V; Blomgren, Klas; Borner, Christoph; Boya, Patricia; Brenner, Catherine; Campanella, Michelangelo; Candi, Eleonora; Carmona-Gutierrez, Didac; Cecconi, Francesco; Chan, Francis K-M; Chandel, Navdeep S; Cheng, Emily H; Chipuk, Jerry E; Cidlowski, John A; Ciechanover, Aaron; Cohen, Gerald M; Conrad, Marcus; Cubillos-Ruiz, Juan R; Czabotar, Peter E; D'Angiolella, Vincenzo; Dawson, Ted M; Dawson, Valina L; De Laurenzi, Vincenzo; De Maria, Ruggero; Debatin, Klaus-Michael; DeBerardinis, Ralph J; Deshmukh, Mohanish; Di Daniele, Nicola; Di Virgilio, Francesco; Dixit, Vishva M; Dixon, Scott J; Duckett, Colin S; Dynlacht, Brian D; El-Deiry, Wafik S; Elrod, John W; Fimia, Gian Maria; Fulda, Simone; García-Sáez, Ana J; Garg, Abhishek D; Garrido, Carmen; Gavathiotis, Evripidis; Golstein, Pierre; Gottlieb, Eyal; Green, Douglas R; Greene, Lloyd A; Gronemeyer, Hinrich; Gross, Atan; Hajnoczky, Gyorgy; Hardwick, J Marie; Harris, Isaac S; Hengartner, Michael O; Hetz, Claudio; Ichijo, Hidenori; Jäättelä, Marja; Joseph, Bertrand; Jost, Philipp J; Juin, Philippe P; Kaiser, William J; Karin, Michael; Kaufmann, Thomas; Kepp, Oliver; Kimchi, Adi; Kitsis, Richard N; Klionsky, Daniel J; Knight, Richard A; Kumar, Sharad; Lee, Sam W; Lemasters, John J; Levine, Beth; Linkermann, Andreas; Lipton, Stuart A; Lockshin, Richard A; López-Otín, Carlos; Lowe, Scott W; Luedde, Tom; Lugli, Enrico; MacFarlane, Marion; Madeo, Frank; Malewicz, Michal; Malorni, Walter; Manic, Gwenola; Marine, Jean-Christophe; Martin, Seamus J; Martinou, Jean-Claude; Medema, Jan Paul; Mehlen, Patrick; Meier, Pascal; Melino, Sonia; Miao, Edward A; Molkentin, Jeffery D; Moll, Ute M; Muñoz-Pinedo, Cristina; Nagata, Shigekazu; Nuñez, Gabriel; Oberst, Andrew; Oren, Moshe; Overholtzer, Michael; Pagano, Michele; Panaretakis, Theocharis; Pasparakis, Manolis; Penninger, Josef M; Pereira, David M; Pervaiz, Shazib; Peter, Marcus E; Piacentini, Mauro; Pinton, Paolo; Prehn, Jochen H M; Puthalakath, Hamsa; Rabinovich, Gabriel A; Rehm, Markus; Rizzuto, Rosario; Rodrigues, Cecilia M P; Rubinsztein, David C; Rudel, Thomas; Ryan, Kevin M; Sayan, Emre; Scorrano, Luca; Shao, Feng; Shi, Yufang; Silke, John; Simon, Hans-Uwe; Sistigu, Antonella; Stockwell, Brent R; Strasser, Andreas; Szabadkai, Gyorgy; Tait, Stephen W G; Tang, Daolin; Tavernarakis, Nektarios; Thorburn, Andrew; Tsujimoto, Yoshihide; Turk, Boris; Vanden Berghe, Tom; Vandenabeele, Peter; Vander Heiden, Matthew G; Villunger, Andreas; Virgin, Herbert W; Vousden, Karen H; Vucic, Domagoj; Wagner, Erwin F; Walczak, Henning; Wallach, David; Wang, Ying; Wells, James A; Wood, Will; Yuan, Junying; Zakeri, Zahra; Zhivotovsky, Boris; Zitvogel, Laurence; Melino, Gerry; Kroemer, Guido

2018-03-01

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

Quantitative mass imaging of single biological macromolecules.

PubMed

Young, Gavin; Hundt, Nikolas; Cole, Daniel; Fineberg, Adam; Andrecka, Joanna; Tyler, Andrew; Olerinyova, Anna; Ansari, Ayla; Marklund, Erik G; Collier, Miranda P; Chandler, Shane A; Tkachenko, Olga; Allen, Joel; Crispin, Max; Billington, Neil; Takagi, Yasuharu; Sellers, James R; Eichmann, Cédric; Selenko, Philipp; Frey, Lukas; Riek, Roland; Galpin, Martin R; Struwe, Weston B; Benesch, Justin L P; Kukura, Philipp

2018-04-27

The cellular processes underpinning life are orchestrated by proteins and their interactions. The associated structural and dynamic heterogeneity, despite being key to function, poses a fundamental challenge to existing analytical and structural methodologies. We used interferometric scattering microscopy to quantify the mass of single biomolecules in solution with 2% sequence mass accuracy, up to 19-kilodalton resolution, and 1-kilodalton precision. We resolved oligomeric distributions at high dynamic range, detected small-molecule binding, and mass-imaged proteins with associated lipids and sugars. These capabilities enabled us to characterize the molecular dynamics of processes as diverse as glycoprotein cross-linking, amyloidogenic protein aggregation, and actin polymerization. Interferometric scattering mass spectrometry allows spatiotemporally resolved measurement of a broad range of biomolecular interactions, one molecule at a time. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Epigenetics of sleep and chronobiology.

PubMed

Qureshi, Irfan A; Mehler, Mark F

2014-03-01

The circadian clock choreographs fundamental biological rhythms. This system is comprised of the master circadian pacemaker in the suprachiasmatic nucleus and associated pacemakers in other tissues that coordinate complex physiological processes and behaviors, such as sleep, feeding, and metabolism. The molecular circuitry that underlies these clocks and orchestrates circadian gene expression has been the focus of intensive investigation, and it is becoming clear that epigenetic factors are highly integrated into these networks. In this review, we draw attention to the fundamental roles played by epigenetic mechanisms in transcriptional and post-transcriptional regulation within the circadian clock system. We also highlight how alterations in epigenetic factors and mechanisms are being linked with sleep-wake disorders. These observations provide important insights into the pathogenesis and potential treatment of these disorders and implicate epigenetic deregulation in the significant but poorly understood interconnections now emerging between circadian processes and neurodegeneration, metabolic diseases, cancer, and aging.

WWWinda Orchestrator: a mechanism for coordinating distributed flocks of Java Applets

NASA Astrophysics Data System (ADS)

Gutfreund, Yechezkal-Shimon; Nicol, John R.

1997-01-01

The WWWinda Orchestrator is a simple but powerful tool for coordinating distributed Java applets. Loosely derived from the Linda programming language developed by David Gelernter and Nicholas Carriero of Yale, WWWinda implements a distributed shared object space called TupleSpace where applets can post, read, or permanently store arbitrary Java objects. In this manner, applets can easily share information without being aware of the underlying communication mechanisms. WWWinda is a very useful for orchestrating flocks of distributed Java applets. Coordination event scan be posted to WWWinda TupleSpace and used to orchestrate the actions of remote applets. Applets can easily share information via the TupleSpace. The technology combines several functions in one simple metaphor: distributed web objects, remote messaging between applets, distributed synchronization mechanisms, object- oriented database, and a distributed event signaling mechanisms. WWWinda can be used a s platform for implementing shared VRML environments, shared groupware environments, controlling remote devices such as cameras, distributed Karaoke, distributed gaming, and shared audio and video experiences.

DDA3 associates with microtubule plus ends and orchestrates microtubule dynamics and directional cell migration

PubMed Central

Zhang, Liangyu; Shao, Hengyi; Zhu, Tongge; Xia, Peng; Wang, Zhikai; Liu, Lifang; Yan, Maomao; Hill, Donald L.; Fang, Guowei; Chen, Zhengjun; Wang, Dongmei; Yao, Xuebiao

2013-01-01

Cell motility and adhesion involve orchestrated interaction of microtubules (MTs) with their plus-end tracking proteins (+TIPs). However, the mechanisms underlying regulations of MT dynamics and directional cell migration are still elusive. Here, we show that DDA3-EB1 interaction orchestrates MT plus-end dynamics and facilitates directional cell migration. Biochemical characterizations reveal that DDA3 interacts with EB1 via its SxIP motif within the C-terminal Pro/Ser-rich region. Time-lapse and total internal reflection fluorescence (TIRF) microscopic assays demonstrate that DDA3 exhibits EB1-dependent, MT plus-end loading and tracking. The EB1-based loading of DDA3 is responsible for MT plus-ends stabilization at the cell cortex, which in turn orchestrates directional cell migration. Interestingly, the DDA3-EB1 interaction is potentially regulated by EB1 acetylation, which may account for physiological regulation underlying EGF-elicited cell migration. Thus, the EB1-based function of DDA3 links MT dynamics to directional cell migration. PMID:23652583

Transforming a Fourth Year Modern Optics Course Using a Deliberate Practice Framework

ERIC Educational Resources Information Center

Jones, David J.; Madison, Kirk W.; Wieman, Carl E.

2015-01-01

We present a study of active learning pedagogies in an upper-division physics course. This work was guided by the principle of deliberate practice for the development of expertise, and this principle was used in the design of the materials and the orchestration of the classroom activities of the students. We present our process for efficiently…

Perceived Needs of At-Risk Families in a Small Town: Implications for Full-Service Community Schools

ERIC Educational Resources Information Center

Voyles, Martha M.

2012-01-01

Researchers agree that a needs assessment is a critical first step in designing a full-service school, but the large task of orchestrating the necessary community collaboration for such projects has occupied most of the literature to date. This study examines the process of planning and implementing a needs assessment for a rural school serving…

AIDing Chromatin and Transcription-Coupled Orchestration of Immunoglobulin Class-Switch Recombination

PubMed Central

Vaidyanathan, Bharat; Yen, Wei-Feng; Pucella, Joseph N.; Chaudhuri, Jayanta

2014-01-01

Secondary diversification of the antibody repertoire upon antigenic challenge, in the form of immunoglobulin heavy chain (IgH) class-switch recombination (CSR) endows mature, naïve B cells in peripheral lymphoid organs with a limitless ability to mount an optimal humoral immune response, thus expediting pathogen elimination. CSR replaces the default constant (CH) region exons (Cμ) of IgH with any of the downstream CH exons (Cγ, Cε, or Cα), thereby altering effector functions of the antibody molecule. This process depends on, and is orchestrated by, activation-induced deaminase (AID), a DNA cytidine deaminase that acts on single-stranded DNA exposed during transcription of switch (S) region sequences at the IgH locus. DNA lesions thus generated are processed by components of several general DNA repair pathways to drive CSR. Given that AID can instigate DNA lesions and genomic instability, stringent checks are imposed that constrain and restrict its mutagenic potential. In this review, we will discuss how AID expression and substrate specificity and activity is rigorously enforced at the transcriptional, post-transcriptional, post-translational, and epigenetic levels, and how the DNA-damage response is choreographed with precision to permit targeted activity while limiting bystander catastrophe. PMID:24734031

Penrose-Hameroff orchestrated objective-reduction proposal for human consciousness is not biologically feasible.

PubMed

McKemmish, Laura K; Reimers, Jeffrey R; McKenzie, Ross H; Mark, Alan E; Hush, Noel S

2009-08-01

Penrose and Hameroff have argued that the conventional models of a brain function based on neural networks alone cannot account for human consciousness, claiming that quantum-computation elements are also required. Specifically, in their Orchestrated Objective Reduction (Orch OR) model [R. Penrose and S. R. Hameroff, J. Conscious. Stud. 2, 99 (1995)], it is postulated that microtubules act as quantum processing units, with individual tubulin dimers forming the computational elements. This model requires that the tubulin is able to switch between alternative conformational states in a coherent manner, and that this process be rapid on the physiological time scale. Here, the biological feasibility of the Orch OR proposal is examined in light of recent experimental studies on microtubule assembly and dynamics. It is shown that the tubulins do not possess essential properties required for the Orch OR proposal, as originally proposed, to hold. Further, we consider also recent progress in the understanding of the long-lived coherent motions in biological systems, a feature critical to Orch OR, and show that no reformation of the proposal based on known physical paradigms could lead to quantum computing within microtubules. Hence, the Orch OR model is not a feasible explanation of the origin of consciousness.

Concise Redox Deracemization of Secondary and Tertiary Amines with a Tetrahydroisoquinoline Core via a Nonenzymatic Process.

PubMed

Ji, Yue; Shi, Lei; Chen, Mu-Wang; Feng, Guang-Shou; Zhou, Yong-Gui

2015-08-26

A concise deracemization of racemic secondary and tertiary amines with a tetrahydroisoquinoline core has been successfully realized by orchestrating a redox process consisted of N-bromosuccinimide oxidation and iridum-catalyzed asymmetric hydrogenation. This compatible redox combination enables one-pot, single-operation deracemization to generate chiral 1-substituted 1,2,3,4-tetrahydroisoquinolines with up to 98% ee in 93% yield, offering a simple and scalable synthetic technique for chiral amines directly from racemic starting materials.

Data Provenance Hybridization Supporting Extreme-Scale Scientific WorkflowApplications

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

Elsethagen, Todd O.; Stephan, Eric G.; Raju, Bibi

As high performance computing (HPC) infrastructures continue to grow in capability and complexity, so do the applications that they serve. HPC and distributed-area computing (DAC) (e.g. grid and cloud) users are looking increasingly toward workflow solutions to orchestrate their complex application coupling, pre- and post-processing needs To gain insight and a more quantitative understanding of a workflow’s performance our method includes not only the capture of traditional provenance information, but also the capture and integration of system environment metrics helping to give context and explanation for a workflow’s execution. In this paper, we describe IPPD’s provenance management solution (ProvEn) andmore » its hybrid data store combining both of these data provenance perspectives.« less

A current affair: electrotherapy in wound healing

PubMed Central

Hunckler, Jerome; de Mel, Achala

2017-01-01

New developments in accelerating wound healing can have immense beneficial socioeconomic impact. The wound healing process is a highly orchestrated series of mechanisms where a multitude of cells and biological cascades are involved. The skin battery and current of injury mechanisms have become topics of interest for their influence in chronic wounds. Electrostimulation therapy of wounds has shown to be a promising treatment option with no-device-related adverse effects. This review presents an overview of the understanding and use of applied electrical current in various aspects of wound healing. Rapid clinical translation of the evolving understanding of biomolecular mechanisms underlying the effects of electrical simulation on wound healing would positively impact upon enhancing patient’s quality of life. PMID:28461755

Online Meta-data Collection and Monitoring Framework for the STAR Experiment at RHIC

NASA Astrophysics Data System (ADS)

Arkhipkin, D.; Lauret, J.; Betts, W.; Van Buren, G.

2012-12-01

The STAR Experiment further exploits scalable message-oriented model principles to achieve a high level of control over online data streams. In this paper we present an AMQP-powered Message Interface and Reliable Architecture framework (MIRA), which allows STAR to orchestrate the activities of Meta-data Collection, Monitoring, Online QA and several Run-Time and Data Acquisition system components in a very efficient manner. The very nature of the reliable message bus suggests parallel usage of multiple independent storage mechanisms for our meta-data. We describe our experience with a robust data-taking setup employing MySQL- and HyperTable-based archivers for meta-data processing. In addition, MIRA has an AJAX-enabled web GUI, which allows real-time visualisation of online process flow and detector subsystem states, and doubles as a sophisticated alarm system when combined with complex event processing engines like Esper, Borealis or Cayuga. The performance data and our planned path forward are based on our experience during the 2011-2012 running of STAR.

Satellite Cells and the Muscle Stem Cell Niche

PubMed Central

Yin, Hang; Price, Feodor

2013-01-01

Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process involving the activation of various cellular and molecular responses. As skeletal muscle stem cells, satellite cells play an indispensible role in this process. The self-renewing proliferation of satellite cells not only maintains the stem cell population but also provides numerous myogenic cells, which proliferate, differentiate, fuse, and lead to new myofiber formation and reconstitution of a functional contractile apparatus. The complex behavior of satellite cells during skeletal muscle regeneration is tightly regulated through the dynamic interplay between intrinsic factors within satellite cells and extrinsic factors constituting the muscle stem cell niche/microenvironment. For the last half century, the advance of molecular biology, cell biology, and genetics has greatly improved our understanding of skeletal muscle biology. Here, we review some recent advances, with focuses on functions of satellite cells and their niche during the process of skeletal muscle regeneration. PMID:23303905

Secure NFV Orchestration Over an SDN-Controlled Optical Network With Time-Shared Quantum Key Distribution Resources

NASA Astrophysics Data System (ADS)

Aguado, Alejandro; Hugues-Salas, Emilio; Haigh, Paul Anthony; Marhuenda, Jaume; Price, Alasdair B.; Sibson, Philip; Kennard, Jake E.; Erven, Chris; Rarity, John G.; Thompson, Mark Gerard; Lord, Andrew; Nejabati, Reza; Simeonidou, Dimitra

2017-04-01

We demonstrate, for the first time, a secure optical network architecture that combines NFV orchestration and SDN control with quantum key distribution (QKD) technology. A novel time-shared QKD network design is presented as a cost-effective solution for practical networks.

Incorporating Wind Excerpts in the School Band Curriculum

ERIC Educational Resources Information Center

Bruns, Robert

2010-01-01

Professional musicians and college students commonly study orchestral excerpts, but a similar practice has yet to be implemented in the band field. Due to their widespread use in orchestral auditions, excerpts have been incorporated as a tool for musical development. Many college professors regularly assign excerpt study as part of their…

Orchestration of Social Modes in E-Learning

ERIC Educational Resources Information Center

Weinberger, Armin; Papadopoulos, Pantelis M.

2016-01-01

The concept of orchestration has recently emerged as a useful metaphor in technology-enhanced learning research communities, because of its explanatory power and appeal in describing how different learning activities, tools, and arrangements could be combined to promote learning. More than a buffet of tools offering possibilities to the teachers,…

Orchestration in Learning Technology Research: Evaluation of a Conceptual Framework

ERIC Educational Resources Information Center

Prieto, Luis P.; Dimitriadis, Yannis; Asensio-Pérez, Juan I.; Looi, Chee-Kit

2015-01-01

The term "orchestrating learning" is being used increasingly often, referring to the coordination activities performed while applying learning technologies to authentic settings. However, there is little consensus about how this notion should be conceptualised, and what aspects it entails. In this paper, a conceptual framework for…

Webbing and Orchestration. Two Interrelated Views on Digital Tools in Mathematics Education

ERIC Educational Resources Information Center

Trouche, Luc; Drijvers, Paul

2014-01-01

The integration of digital tools in mathematics education is considered both promising and problematic. To deal with this issue, notions of "webbing" and "instrumental orchestration" are developed. However, the two seemed to be disconnected, and having different cultural and theoretical roots. In this article, we investigate…

Roles of Teachers in Orchestrating Learning in Elementary Science Classrooms

ERIC Educational Resources Information Center

Zhai, Junqing; Tan, Aik-Ling

2015-01-01

This study delves into the different roles that elementary science teachers play in the classroom to orchestrate science learning opportunities for students. Examining the classroom practices of three elementary science teachers in Singapore, we found that teachers shuttle between four key roles in enabling student learning in science. Teachers…

Strings in General Music: An Experience with Multiple Sequencing

ERIC Educational Resources Information Center

Martin, Jeffrey

2012-01-01

Instrumental performance that approximates real-world models is one way in which a general music curriculum can encourage high levels of engagement and potential for lifelong musical activity. Although guitars, keyboards, and various folk instruments are useful for this purpose, orchestral instruments can also provide significant solo and ensemble…

Model-Driven Design: Systematically Building Integrated Blended Learning Experiences

ERIC Educational Resources Information Center

Laster, Stephen

2010-01-01

Developing and delivering curricula that are integrated and that use blended learning techniques requires a highly orchestrated design. While institutions have demonstrated the ability to design complex curricula on an ad-hoc basis, these projects are generally successful at a great human and capital cost. Model-driven design provides a…

An Argument Everyone Wins: Shared Learning Unites Teachers across Schools and Grade Levels

ERIC Educational Resources Information Center

Goldberg, Lauren; Siegel, Brad; Goldberg, Gravity

2015-01-01

The three authors of this article--a K-12 regional director of curriculum, instruction, and assessment responsible for orchestrating professional learning, a high school English teacher who participated in the professional learning, and an independent literacy consultant who supports four districts' professional learning--share their experiences…

The interferon-dependent orchestration of innate and adaptive immunity after transplantation.

PubMed

Robb, Renee J; Hill, Geoffrey R

2012-06-07

The therapeutic GVL effect after allogeneic stem cell transplantation is limited by the development of GVHD. The ultimate aim of current research is to separate the 2 processes in a meaningful fashion. The IFNs are a pleiotropic group of cytokines that were originally recognized because of their ability to interfere with viral replication. However, it is now established that these cytokines play an important role in orchestrating both innate and adaptive immunity. Multiple studies have investigated the effects of both types I and II IFN on GVHD and GVL in preclinical transplant models. The results indicate variable effects that are dependent on the period of activity within the developing immune response, the presence and type of pretransplant conditioning and the differential mechanisms, and IFN sensitivity of immune pathology within individual target organs during GVHD. This Perspective discusses the current literature on the IFNs and their potential modulation within clinical transplantation, focusing particularly on enhancing the therapeutic GVL effects.

Optimizing the Orchestration of Resemiotization with Teacher "Talk Moves": A Model of Guided-Inquiry Instruction in Middle School Science

ERIC Educational Resources Information Center

Millstone, Rachel Diana

2010-01-01

The current conceptualization of science set forth by the National Research Council (2008) is one of science as a social activity, rather than a view of science as a fixed body of knowledge. This requires teachers to consider how communication, processing, and meaning-making contribute to science learning. It also requires teachers to think deeply…

Culture, Structure and Leadership Impacts on Gender Inclusion in the Security Sector

DTIC Science & Technology

2017-09-01

culture were outcomes of structural reform. A guided evolution in security sector culture occurred following persistent social pressure, compliance...brought about a change in national and organizational culture to address socially complex issues. As the orchestrators of large successful corporate...challenges them (Jolly 2002). In the process, we are influenced and shaped as we interact with local, national and international information. Likewise, we

Using School Performance Data to Drive School and Education District Office Accountability and Improvement: The Case of Ghana

ERIC Educational Resources Information Center

Prew, Martin; Quaigrain, Kenneth

2010-01-01

This article looks at a school management tool that allows school managers and education district offices to review the performance of their schools and use the broad-based data to undertake orchestrated planning with districts planning delivery based on the needs of schools and in support of school improvement plans. The review process also…

Orchestrating Semiotic Leaps from Tacit to Cultural Quantitative Reasoning--The Case of Anticipating Experimental Outcomes of a Quasi-Binomial Random Generator

ERIC Educational Resources Information Center

Abrahamson, Dor

2009-01-01

This article reports on a case study from a design-based research project that investigated how students make sense of the disciplinary tools they are taught to use, and specifically, what personal, interpersonal, and material resources support this process. The probability topic of binomial distribution was selected due to robust documentation of…

Transcriptional regulation of podocyte specification and differentiation.

PubMed

Quaggin, Susan E

2002-05-15

Glomerular visceral epithelial cells (podocytes) are highly specialized cells found in the vertebrate and invertebrate kidney and make up a major portion of the filtration barrier between blood and urinary spaces. During development, specification and differentiation of the podocyte lineage must be tightly orchestrated to produce highly specialized characteristics such as foot processes and slit diaphragms. Furthermore, podocytes are poised to direct incoming endothelial and mesangial cells during glomerular development. They express a number of growth factors that likely play a major role in these processes. Recent findings from transgenic and knockout mouse models and the identification of genes responsible for human podocyte disease have provided insight into transcriptional regulation of some of these processes. These transcription factors include Pax2, WT1 (the Wilms tumor suppressor gene), Pod1 (capsulin, epicardin), Kreisler (maf-1), lmx1b, and mf2. Furthermore, regulatory regions from a podocyte-restricted gene, NPHS1 (nephrin) that are required to direct podocyte-specific expression have been identified from both human and murine genes and provide a tool to further dissect the transcriptional regulation of podocyte-specific gene expression. This article reviews the present state of knowledge regarding transcriptional regulation of podocyte specification and differentiation. Copyright 2002 Wiley-Liss, Inc.

Multimodal Teaching Analytics: Automated Extraction of Orchestration Graphs from Wearable Sensor Data

ERIC Educational Resources Information Center

Prieto, L. P.; Sharma, K.; Kidzinski, L.; Rodríguez-Triana, M. J.; Dillenbourg, P.

2018-01-01

The pedagogical modelling of everyday classroom practice is an interesting kind of evidence, both for educational research and teachers' own professional development. This paper explores the usage of wearable sensors and machine learning techniques to automatically extract orchestration graphs (teaching activities and their social plane over time)…

Generic Service Integration in Adaptive Learning Experiences Using IMS Learning Design

ERIC Educational Resources Information Center

de-la-Fuente-Valentin, Luis; Pardo, Abelardo; Kloos, Carlos Delgado

2011-01-01

IMS Learning Design is a specification to capture the orchestration taking place in a learning scenario. This paper presents an extension called Generic Service Integration. This paradigm allows a bidirectional communication between the course engine in charge of the orchestration and conventional Web 2.0 tools. This communication allows the…

Instructional Design or School Politics? A Discussion of "Orchestration" in TEL Research

ERIC Educational Resources Information Center

Perrotta, C.; Evans, M. A.

2013-01-01

This paper argues that the emphasis on orchestration as a metaphor for teaching in technology-enhanced learning (TEL) environments, featured in recent academic discussions, is an opportunity to broaden the scope of the inquiry into educational technology. Drawing on sociological literature and research that investigated the systemic factors that…

Kindergarten Teachers' Orchestration of Mathematical Activities Afforded by Technology: Agency and Mediation

ERIC Educational Resources Information Center

Carlsen, Martin; Erfjord, Ingvald; Hundeland, Per Sigurd; Monaghan, John

2016-01-01

This paper focuses on kindergarten teachers' interactions with young children during mathematical learning activities involving the use of digital tools. We aim to characterise the teachers' roles and actions in these activities and extend considerations of teachers' orchestrations current in the research literature with regard to agency and…

Metabolic alterations in developing brain after injury – knowns and unknowns

PubMed Central

McKenna, Mary C.; Scafidi, Susanna; Robertson, Courtney L.

2016-01-01

Brain development is a highly orchestrated complex process. The developing brain utilizes many substrates including glucose, ketone bodies, lactate, fatty acids and amino acids for energy, cell division and the biosynthesis of nucleotides, proteins and lipids. Metabolism is crucial to provide energy for all cellular processes required for brain development and function including ATP formation, synaptogenesis, synthesis, release and uptake of neurotransmitters, maintaining ionic gradients and redox status, and myelination. The rapidly growing population of infants and children with neurodevelopmental and cognitive impairments and life-long disability resulting from developmental brain injury is a significant public health concern. Brain injury in infants and children can have devastating effects because the injury is superimposed on the high metabolic demands of the developing brain. Acute injury in the pediatric brain can derail, halt or lead to dysregulation of the complex and highly regulated normal developmental processes. This paper provides a brief review of metabolism in developing brain and alterations found clinically and in animal models of developmental brain injury. The metabolic changes observed in three major categories of injury that can result in life-long cognitive and neurological disabilities, including neonatal hypoxia-ischemia, pediatric traumatic brain injury, and brain injury secondary to prematurity are reviewed. PMID:26148530

Agile battle management efficiency for command, control, communications, computers and intelligence (C4I)

NASA Astrophysics Data System (ADS)

Blasch, Erik; Bélanger, Micheline

2016-05-01

Various operations such as civil-military co-operation (CIMIC) affairs require orchestration of communications, assets, and actors. A key component includes technology advancements to enable coordination among people and machines the ability to know where things are, who to coordinate with, and open and consistent lines of communication. In this paper, we explore concepts of battle management (BM) to support high-tempo emergency response scenarios such as a disaster action response team (DART). Three concepts highlighted of agile battle management (ABM) include source orchestration (e.g., sensors and domains), battle management language (BML) development (e.g., software and ontologies), and command and control (C2) coordination (e.g., people and visualization); which require correlation and de-confliction. These concepts of ABM support the physical, information, and cognitive domains for efficient command, control, communications, and information (C3I) to synchronize data and people for efficient and effective operations.

Design and implementation of a non-linear symphonic soundtrack of a video game

NASA Astrophysics Data System (ADS)

Sporka, Adam J.; Valta, Jan

2017-10-01

The music in the contemporary video games is often interactive. The music playback is based on transitions between pieces of available music material. These transitions happen in response to evolving gameplay. This paradigm is referred to as the adaptive music. Our challenge was to design, create, and implement the soundtrack of the upcoming video game Kingdom Come: Deliverance. Our soundtrack is a collection of compositions with symphonic orchestration. Per our design decision, our intention was to implement the adaptive music in a way which respected the nature of the orchestral film score. We created our own adaptive music middleware, called Sequence Music Engine, implementing a high-level music logic as well as the low-level playback infrastructure. Our system can handle hours of video game music, helps maintain the relevance of the music throughout the video game, and minimises the repetitiveness of the individual pieces.

Cloning the Professor, an Alternative to Ineffective Teaching in a Large Course

ERIC Educational Resources Information Center

Nelson, Jennifer; Robison, Diane F.; Bell, John D.; Bradshaw, William S.

2009-01-01

Pedagogical strategies have been experimentally applied in large-enrollment biology courses in an attempt to amplify what teachers do best in effecting deep learning, thus more closely approximating a one-on-one interaction with students. Carefully orchestrated in-class formative assessments were conducted to provide frequent, high-quality…

Pharmacodynamic Assay Panel for Monitoring Phospho-Signaling Networks | Office of Cancer Clinical Proteomics Research

Cancer.gov

The DNA damage response (DDR) is a highly regulated signal transduction network that orchestrates the temporal and spatial organization of protein complexes required to repair (or tolerate) DNA damage (e.g., nucleotide excision repair, base excision repair, homologous recombination, non-homologous end joining, post-replication repair).

AMOEBA: Designing for Collaboration in Computer Science Classrooms through Live Learning Analytics

ERIC Educational Resources Information Center

Berland, Matthew; Davis, Don; Smith, Carmen Petrick

2015-01-01

AMOEBA is a unique tool to support teachers' orchestration of collaboration among novice programmers in a non-traditional programming environment. The AMOEBA tool was designed and utilized to facilitate collaboration in a classroom setting in real time among novice middle school and high school programmers utilizing the IPRO programming…

Beyond Prediction: First Steps toward Automatic Intervention in MOOC Student Stopout

ERIC Educational Resources Information Center

Whitehill, Jacob; Williams, Joseph; Lopez, Glenn; Coleman, Cody; Reich, Justin

2015-01-01

High attrition rates in massive open online courses (MOOCs) have motivated growing interest in the automatic detection of student "stopout". Stopout classifiers can be used to orchestrate an intervention before students quit, and to survey students dynamically about why they ceased participation. In this paper we expand on existing…

Roles of CDK and DDK in Genome Duplication and Maintenance: Meiotic Singularities.

PubMed

Gómez-Escoda, Blanca; Wu, Pei-Yun Jenny

2017-03-20

Cells reproduce using two types of divisions: mitosis, which generates two daughter cells each with the same genomic content as the mother cell, and meiosis, which reduces the number of chromosomes of the parent cell by half and gives rise to four gametes. The mechanisms that promote the proper progression of the mitotic and meiotic cycles are highly conserved and controlled. They require the activities of two types of serine-threonine kinases, the cyclin-dependent kinases (CDKs) and the Dbf4-dependent kinase (DDK). CDK and DDK are essential for genome duplication and maintenance in both mitotic and meiotic divisions. In this review, we aim to highlight how these kinases cooperate to orchestrate diverse processes during cellular reproduction, focusing on meiosis-specific adaptions of their regulation and functions in DNA metabolism.

Identification of Modules in Protein-Protein Interaction Networks

NASA Astrophysics Data System (ADS)

Erten, Sinan; Koyutürk, Mehmet

In biological systems, most processes are carried out through orchestration of multiple interacting molecules. These interactions are often abstracted using network models. A key feature of cellular networks is their modularity, which contributes significantly to the robustness, as well as adaptability of biological systems. Therefore, modularization of cellular networks is likely to be useful in obtaining insights into the working principles of cellular systems, as well as building tractable models of cellular organization and dynamics. A common, high-throughput source of data on molecular interactions is in the form of physical interactions between proteins, which are organized into protein-protein interaction (PPI) networks. This chapter provides an overview on identification and analysis of functional modules in PPI networks, which has been an active area of research in the last decade.

Chemical chronobiology: Toward drugs manipulating time.

PubMed

Wallach, Thomas; Kramer, Achim

2015-06-22

Circadian clocks are endogenous timing systems orchestrating the daily regulation of a huge variety of physiological, metabolic and behavioral processes. These clocks are important for health - in mammals, their disruption leads to a diverse number of pathologies. While genetic and biochemical approaches largely uncovered the molecular bases of circadian rhythm generation, chemical biology strategies targeting the circadian oscillator by small chemical compounds are increasingly developed. Here, we review the recent progress in the identification of small molecules modulating circadian rhythms. We focus on high-throughput screening approaches using circadian bioluminescence reporter cell lines as well as describe alternative mechanistic screens. Furthermore, we discuss the potential for chemical optimization of small molecule ligands with regard to the recent progress in structural chronobiology. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

First field demonstration of cloud datacenter workflow automation employing dynamic optical transport network resources under OpenStack and OpenFlow orchestration.

PubMed

Szyrkowiec, Thomas; Autenrieth, Achim; Gunning, Paul; Wright, Paul; Lord, Andrew; Elbers, Jörg-Peter; Lumb, Alan

2014-02-10

For the first time, we demonstrate the orchestration of elastic datacenter and inter-datacenter transport network resources using a combination of OpenStack and OpenFlow. Programmatic control allows a datacenter operator to dynamically request optical lightpaths from a transport network operator to accommodate rapid changes of inter-datacenter workflows.

STTEPping in the Right Direction? Western Classical Music in an Orchestral Programme for Disadvantaged African Youth

ERIC Educational Resources Information Center

van Niekerk, Caroline; Salminen, Sanna

2008-01-01

This article looks at STTEP, an outreach project currently housed at the University of Pretoria, which concentrates on the teaching of western orchestral instruments, plus background areas such as music theory, to disadvantaged children and youth from a variety of townships around Pretoria, South Africa. STTEP's direction can well be described as…

BPELPower—A BPEL execution engine for geospatial web services

NASA Astrophysics Data System (ADS)

Yu, Genong (Eugene); Zhao, Peisheng; Di, Liping; Chen, Aijun; Deng, Meixia; Bai, Yuqi

2012-10-01

The Business Process Execution Language (BPEL) has become a popular choice for orchestrating and executing workflows in the Web environment. As one special kind of scientific workflow, geospatial Web processing workflows are data-intensive, deal with complex structures in data and geographic features, and execute automatically with limited human intervention. To enable the proper execution and coordination of geospatial workflows, a specially enhanced BPEL execution engine is required. BPELPower was designed, developed, and implemented as a generic BPEL execution engine with enhancements for executing geospatial workflows. The enhancements are especially in its capabilities in handling Geography Markup Language (GML) and standard geospatial Web services, such as the Web Processing Service (WPS) and the Web Feature Service (WFS). BPELPower has been used in several demonstrations over the decade. Two scenarios were discussed in detail to demonstrate the capabilities of BPELPower. That study showed a standard-compliant, Web-based approach for properly supporting geospatial processing, with the only enhancement at the implementation level. Pattern-based evaluation and performance improvement of the engine are discussed: BPELPower directly supports 22 workflow control patterns and 17 workflow data patterns. In the future, the engine will be enhanced with high performance parallel processing and broad Web paradigms.

Orchestrating TRANSP Simulations for Interpretative and Predictive Tokamak Modeling with OMFIT

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

Grierson, B. A.; Yuan, X.; Gorelenkova, M.

TRANSP simulations are being used in the OMFIT work- flow manager to enable a machine independent means of experimental analysis, postdictive validation, and predictive time dependent simulations on the DIII-D, NSTX, JET and C-MOD tokamaks. The procedures for preparing the input data from plasma profile diagnostics and equilibrium reconstruction, as well as processing of the time-dependent heating and current drive sources and assumptions about the neutral recycling, vary across machines, but are streamlined by using a common workflow manager. Settings for TRANSP simulation fidelity are incorporated into the OMFIT framework, contrasting between-shot analysis, power balance, and fast-particle simulations. A previouslymore » established series of data consistency metrics are computed such as comparison of experimental vs. calculated neutron rate, equilibrium stored energy vs. total stored energy from profile and fast-ion pressure, and experimental vs. computed surface loop voltage. Discrepancies between data consistency metrics can indicate errors in input quantities such as electron density profile or Zeff, or indicate anomalous fast-particle transport. Measures to assess the sensitivity of the verification metrics to input quantities are provided by OMFIT, including scans of the input profiles and standardized post-processing visualizations. For predictive simulations, TRANSP uses GLF23 or TGLF to predict core plasma profiles, with user defined boundary conditions in the outer region of the plasma. ITPA validation metrics are provided in post-processing to assess the transport model validity. By using OMFIT to orchestrate the steps for experimental data preparation, selection of operating mode, submission, post-processing and visualization, we have streamlined and standardized the usage of TRANSP.« less

Orchestrating TRANSP Simulations for Interpretative and Predictive Tokamak Modeling with OMFIT

DOE PAGES

Grierson, B. A.; Yuan, X.; Gorelenkova, M.; ...

2018-02-21

TRANSP simulations are being used in the OMFIT work- flow manager to enable a machine independent means of experimental analysis, postdictive validation, and predictive time dependent simulations on the DIII-D, NSTX, JET and C-MOD tokamaks. The procedures for preparing the input data from plasma profile diagnostics and equilibrium reconstruction, as well as processing of the time-dependent heating and current drive sources and assumptions about the neutral recycling, vary across machines, but are streamlined by using a common workflow manager. Settings for TRANSP simulation fidelity are incorporated into the OMFIT framework, contrasting between-shot analysis, power balance, and fast-particle simulations. A previouslymore » established series of data consistency metrics are computed such as comparison of experimental vs. calculated neutron rate, equilibrium stored energy vs. total stored energy from profile and fast-ion pressure, and experimental vs. computed surface loop voltage. Discrepancies between data consistency metrics can indicate errors in input quantities such as electron density profile or Zeff, or indicate anomalous fast-particle transport. Measures to assess the sensitivity of the verification metrics to input quantities are provided by OMFIT, including scans of the input profiles and standardized post-processing visualizations. For predictive simulations, TRANSP uses GLF23 or TGLF to predict core plasma profiles, with user defined boundary conditions in the outer region of the plasma. ITPA validation metrics are provided in post-processing to assess the transport model validity. By using OMFIT to orchestrate the steps for experimental data preparation, selection of operating mode, submission, post-processing and visualization, we have streamlined and standardized the usage of TRANSP.« less

Influences of Teacher Delivery, Student Engagement, and Observation Focus on Preservice Teachers' Perceptions of Teaching Effectiveness

ERIC Educational Resources Information Center

Napoles, Jessica; MacLeod, Rebecca B.

2016-01-01

The purpose of this study was to examine how teacher delivery, student engagement, and observation focus influenced preservice teachers' ratings of teaching effectiveness. Participants (N = 84 preservice teachers) viewed short teaching excerpts of orchestral and choral rehearsals wherein the teacher displayed either high or low teacher delivery,…

Activation and Resolution of Periodontal Inflammation and Its Systemic Impact

PubMed Central

Hasturk, Hatice; Kantarci, Alpdogan

2015-01-01

Inflammation is a highly organized event impacting upon organs, tissues and biological systems. Periodontal diseases are characterized by dysregulation or dysfunction of resolution pathways of inflammation resulting in a failure of healing and a dominant chronic, progressive, destructive and predominantly unresolved inflammation. The biological consequences of inflammatory processes may be independent of the etiological agents such as trauma, microbial organisms and stress. The impact of the inflammatory pathological process depends upon the affected tissues or organ system. Whilst mediators are similar, there is a tissue specificity for the inflammatory events. It is plausible that inflammatory processes in one organ could directly lead to pathologies in another organ or tissue. Communication between distant parts of the body and their inflammatory status is also mediated by common signaling mechanisms mediated via cells and soluble mediators. This review focuses on periodontal inflammation, its systemic associations and advances in therapeutic approaches based on mediators acting through orchestration of natural pathway to resolution of inflammation. We also discuss a new treatment concept where natural pathways of resolution of periodontal inflammation can be used to limit systemic inflammation and promote healing and regeneration. PMID:26252412

EGF induces epithelial-mesenchymal transition and cancer stem-like cell properties in human oral cancer cells via promoting Warburg effect.

PubMed

Xu, Qilin; Zhang, Qunzhou; Ishida, Yasutaka; Hajjar, Souren; Tang, Xudong; Shi, Haoran; Dang, Chi V; Le, Anh D

2017-02-07

"Warburg effect", the enhanced glycolysis or aerobic glycolysis, confers cancer cells the ability to survive and proliferate even under stressed conditions. In this study, we explored the role of epidermal growth factor (EGF) in orchestrating Warburg effect, the epithelial-mesenchymal transition (EMT) process, and the acquisition of cancer stem-like cell properties in human oral squamous cell carcinoma (OSCC) cells. Our results showed that EGF induces EMT process in OSCC cells, which correlates with the acquisition of cancer stem-like properties, including the enrichment of CD44+/CD24- population of cancer cells and an increased expression of CSC-related genes, aldehyde dehydrogenase-1 (ALDH1) and Bmi-1. We also showed that EGF concomitantly enhanced L-lactate production, while blocking glycolysis by 2-deoxy-D-glucose (2-DG) robustly reversed EGF-induced EMT process and CSC-like properties in OSCC cells. Mechanistically, we demonstrated that EGF promoted EMT process and CSC generation through EGFR/PI3K/HIF-1α axis-orchestrated glycolysis. Using an orthotopic tumor model of human OSCC (UM-SCC1) injected in the tongue of BALB/c nude mice, we showed that treatment with 2-DG in vivo significantly inhibited the metastasis of tumor cells to the regional cervical lymph nodes and reduced the expression of ALDH1 and vimentin in both in situ tumors and tumor cell-invaded regional lymph nodes. Taken together, these findings have unveiled a new mechanism that EGF drives OSCC metastasis through induction of EMT process and CSC generation, which is driven by an enhanced glycolytic metabolic program in OSCC cells.

Predicting protein amidation sites by orchestrating amino acid sequence features

NASA Astrophysics Data System (ADS)

Zhao, Shuqiu; Yu, Hua; Gong, Xiujun

2017-08-01

Amidation is the fourth major category of post-translational modifications, which plays an important role in physiological and pathological processes. Identifying amidation sites can help us understanding the amidation and recognizing the original reason of many kinds of diseases. But the traditional experimental methods for predicting amidation sites are often time-consuming and expensive. In this study, we propose a computational method for predicting amidation sites by orchestrating amino acid sequence features. Three kinds of feature extraction methods are used to build a feature vector enabling to capture not only the physicochemical properties but also position related information of the amino acids. An extremely randomized trees algorithm is applied to choose the optimal features to remove redundancy and dependence among components of the feature vector by a supervised fashion. Finally the support vector machine classifier is used to label the amidation sites. When tested on an independent data set, it shows that the proposed method performs better than all the previous ones with the prediction accuracy of 0.962 at the Matthew's correlation coefficient of 0.89 and area under curve of 0.964.

Inter-dependent apical microtubule and actin dynamics orchestrate centrosome retention and neuronal delamination

PubMed Central

Kasioulis, Ioannis

2017-01-01

Detachment of newborn neurons from the neuroepithelium is required for correct neuronal architecture and functional circuitry. This process, also known as delamination, involves adherens-junction disassembly and acto-myosin-mediated abscission, during which the centrosome is retained while apical/ciliary membranes are shed. Cell-biological mechanisms mediating delamination are, however, poorly understood. Using live-tissue and super-resolution imaging, we uncover a centrosome-nucleated wheel-like microtubule configuration, aligned with the apical actin cable and adherens-junctions within chick and mouse neuroepithelial cells. These microtubules maintain adherens-junctions while actin maintains microtubules, adherens-junctions and apical end-foot dimensions. During neuronal delamination, acto-myosin constriction generates a tunnel-like actin-microtubule configuration through which the centrosome translocates. This movement requires inter-dependent actin and microtubule activity, and we identify drebrin as a potential coordinator of these cytoskeletal dynamics. Furthermore, centrosome compromise revealed that this organelle is required for delamination. These findings identify new cytoskeletal configurations and regulatory relationships that orchestrate neuronal delamination and may inform mechanisms underlying pathological epithelial cell detachment. PMID:29058679

Interactive Whiteboards and All that Jazz: The Contribution of Musical Metaphors to the Analysis of Classroom Activity with Interactive Technologies

ERIC Educational Resources Information Center

Beauchamp, Gary; Kennewell, Steve; Tanner, Howard; Jones, Sonia

2010-01-01

The teacher's role has often been described as one of "orchestration", and this musical analogy is a powerful one in characterising the manipulation of features in the classroom setting in order to generate activity or "performance" which leads to learning. However, a classical view of orchestration would fail to recognise the extent to which…

TAMU: A New Space Mission Operations Paradigm

NASA Technical Reports Server (NTRS)

Meshkat, Leila; Ruszkowski, James; Haensly, Jean; Pennington, Granvil A.; Hogle, Charles

2011-01-01

The Transferable, Adaptable, Modular and Upgradeable (TAMU) Flight Production Process (FPP) is a model-centric System of System (SoS) framework which cuts across multiple organizations and their associated facilities, that are, in the most general case, in geographically diverse locations, to develop the architecture and associated workflow processes for a broad range of mission operations. Further, TAMU FPP envisions the simulation, automatic execution and re-planning of orchestrated workflow processes as they become operational. This paper provides the vision for the TAMU FPP paradigm. This includes a complete, coherent technique, process and tool set that result in an infrastructure that can be used for full lifecycle design and decision making during any flight production process. A flight production process is the process of developing all products that are necessary for flight.

Towards engineering of hormonal crosstalk in plant immunity.

PubMed

Shigenaga, Alexandra M; Berens, Matthias L; Tsuda, Kenichi; Argueso, Cristiana T

2017-08-01

Plant hormones regulate physiological responses in plants, including responses to pathogens and beneficial microbes. The last decades have provided a vast amount of evidence about the contribution of different plant hormones to plant immunity, and also of how they cooperate to orchestrate immunity activation, in a process known as hormone crosstalk. In this review we highlight the complexity of hormonal crosstalk in immunity and approaches currently being used to further understand this process, as well as perspectives to engineer hormone crosstalk for enhanced pathogen resistance and overall plant fitness. Copyright © 2017 Elsevier Ltd. All rights reserved.

Blood banking and transfusion medicine for the apheresis medicine practitioner.

PubMed

Jeffus, Susanne; Wehrli, Gay

2012-01-01

This article provides a concise overview of blood banking and transfusion medicine (BBTM) for the therapeutic apheresis medicine practitioner. It addresses the complete pathway from blood donor qualification to blood collection, to processing and storing blood components, to patient testing, to ordering blood components for therapeutic apheresis (TA) procedures, to preparing the component for transfusion, and finally to transfusion. The nurses, technologists, and physicians orchestrate these activities in concert to best serve patients undergoing TA procedures. Enhancing knowledge of these processes may improve the quality of patient care and the utilization of blood products. Copyright © 2012 Wiley Periodicals, Inc.

Population evacuations in industrial accidents: a review of the literature about four major events.

PubMed

Soffer, Yechiel; Schwartz, Dagan; Goldberg, Avishay; Henenfeld, Maxim; Bar-Dayan, Yaron

2008-01-01

This article reviews the literature describing four chemical and nuclear accidents and the lessons learned from each regarding the evacuation of civilian populations. Evacuation may save lives however, if poorly orchestrated, it may cause serious problems. For example, an inaccurate assessment of danger may lead to the evacuation of the same population twice, as the area requiring evacuation becomes larger than originally expected. Evacuation programs should focus on the vulnerable components of the populations, such as the elderly, children, and the disabled, and also should include plans for the care of pets and other animals. Training programs for civilians living near industrial centers and other high-risk areas should be considered. Finally, pre-event planning and preparation can improve the evacuation process and prevent panic behavior, and thus result in fewer casualties.

Diversity in TAF proteomics: consequences for cellular differentiation and migration.

PubMed

Kazantseva, Jekaterina; Palm, Kaia

2014-09-19

Development is a highly controlled process of cell proliferation and differentiation driven by mechanisms of dynamic gene regulation. Specific DNA binding factors for establishing cell- and tissue-specific transcriptional programs have been characterised in different cell and animal models. However, much less is known about the role of "core transcription machinery" during cell differentiation, given that general transcription factors and their spatiotemporally patterned activity govern different aspects of cell function. In this review, we focus on the role of TATA-box associated factor 4 (TAF4) and its functional isoforms generated by alternative splicing in controlling lineage-specific differentiation of normal mesenchymal stem cells and cancer stem cells. In the light of our recent findings, induction, control and maintenance of cell differentiation status implies diversification of the transcription initiation apparatus orchestrated by alternative splicing.

Mitochondrial dynamics in the regulation of neurogenesis: From development to the adult brain.

PubMed

Khacho, Mireille; Slack, Ruth S

2018-01-01

Mitochondria are classically known to be the cellular energy producers, but a renewed appreciation for these organelles has developed with the accumulating discoveries of additional functions. The importance of mitochondria within the brain has been long known, particularly given the high-energy demanding nature of neurons. The energy demands imposed by neurons require the well-orchestrated morphological adaptation and distribution of mitochondria. Recent studies now reveal the importance of mitochondrial dynamics not only in mature neurons but also during neural development, particularly during the process of neurogenesis and neural stem cell fate decisions. In this review, we will highlight the recent findings that illustrate the importance of mitochondrial dynamics in neurodevelopment and neural stem cell function. Developmental Dynamics 247:47-53, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Load-sensitive dynamic workflow re-orchestration and optimisation for faster patient healthcare.

PubMed

Meli, Christopher L; Khalil, Ibrahim; Tari, Zahir

2014-01-01

Hospital waiting times are considerably long, with no signs of reducing any-time soon. A number of factors including population growth, the ageing population and a lack of new infrastructure are expected to further exacerbate waiting times in the near future. In this work, we show how healthcare services can be modelled as queueing nodes, together with healthcare service workflows, such that these workflows can be optimised during execution in order to reduce patient waiting times. Services such as X-ray, computer tomography, and magnetic resonance imaging often form queues, thus, by taking into account the waiting times of each service, the workflow can be re-orchestrated and optimised. Experimental results indicate average waiting time reductions are achievable by optimising workflows using dynamic re-orchestration. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

Orchestration of Molecular Information through Higher Order Chemical Recognition

NASA Astrophysics Data System (ADS)

Frezza, Brian M.

Broadly defined, higher order chemical recognition is the process whereby discrete chemical building blocks capable of specifically binding to cognate moieties are covalently linked into oligomeric chains. These chains, or sequences, are then able to recognize and bind to their cognate sequences with a high degree of cooperativity. Principally speaking, DNA and RNA are the most readily obtained examples of this chemical phenomenon, and function via Watson-Crick cognate pairing: guanine pairs with cytosine and adenine with thymine (DNA) or uracil (RNA), in an anti-parallel manner. While the theoretical principles, techniques, and equations derived herein apply generally to any higher-order chemical recognition system, in practice we utilize DNA oligomers as a model-building material to experimentally investigate and validate our hypotheses. Historically, general purpose information processing has been a task limited to semiconductor electronics. Molecular computing on the other hand has been limited to ad hoc approaches designed to solve highly specific and unique computation problems, often involving components or techniques that cannot be applied generally in a manner suitable for precise and predictable engineering. Herein, we provide a fundamental framework for harnessing high-order recognition in a modular and programmable fashion to synthesize molecular information process networks of arbitrary construction and complexity. This document provides a solid foundation for routinely embedding computational capability into chemical and biological systems where semiconductor electronics are unsuitable for practical application.

Hypertrophic scar contracture is mediated by the TRPC3 mechanical force transducer via NFkB activation

PubMed Central

Ishise, Hisako; Larson, Barrett; Hirata, Yutaka; Fujiwara, Toshihiro; Nishimoto, Soh; Kubo, Tateki; Matsuda, Ken; Kanazawa, Shigeyuki; Sotsuka, Yohei; Fujita, Kazutoshi; Kakibuchi, Masao; Kawai, Kenichiro

2015-01-01

Wound healing process is a complex and highly orchestrated process that ultimately results in the formation of scar tissue. Hypertrophic scar contracture is considered to be a pathologic and exaggerated wound healing response that is known to be triggered by repetitive mechanical forces. We now show that Transient Receptor Potential (TRP) C3 regulates the expression of fibronectin, a key regulatory molecule involved in the wound healing process, in response to mechanical strain via the NFkB pathway. TRPC3 is highly expressed in human hypertrophic scar tissue and mechanical stimuli are known to upregulate TRPC3 expression in human skin fibroblasts in vitro. TRPC3 overexpressing fibroblasts subjected to repetitive stretching forces showed robust expression levels of fibronectin. Furthermore, mechanical stretching of TRPC3 overexpressing fibroblasts induced the activation of nuclear factor-kappa B (NFκB), a regulator fibronectin expression, which was able to be attenuated by pharmacologic blockade of either TRPC3 or NFκB. Finally, transplantation of TRPC3 overexpressing fibroblasts into mice promoted wound contraction and increased fibronectin levels in vivo. These observations demonstrate that mechanical stretching drives fibronectin expression via the TRPC3-NFkB axis, leading to intractable wound contracture. This model explains how mechanical strain on cutaneous wounds might contribute to pathologic scarring. PMID:26108359

search GenBank: interactive orchestration and ad-hoc choreography of Web services in the exploration of the biomedical resources of the National Center For Biotechnology Information

PubMed Central

2013-01-01

Background Due to the growing number of biomedical entries in data repositories of the National Center for Biotechnology Information (NCBI), it is difficult to collect, manage and process all of these entries in one place by third-party software developers without significant investment in hardware and software infrastructure, its maintenance and administration. Web services allow development of software applications that integrate in one place the functionality and processing logic of distributed software components, without integrating the components themselves and without integrating the resources to which they have access. This is achieved by appropriate orchestration or choreography of available Web services and their shared functions. After the successful application of Web services in the business sector, this technology can now be used to build composite software tools that are oriented towards biomedical data processing. Results We have developed a new tool for efficient and dynamic data exploration in GenBank and other NCBI databases. A dedicated search GenBank system makes use of NCBI Web services and a package of Entrez Programming Utilities (eUtils) in order to provide extended searching capabilities in NCBI data repositories. In search GenBank users can use one of the three exploration paths: simple data searching based on the specified user’s query, advanced data searching based on the specified user’s query, and advanced data exploration with the use of macros. search GenBank orchestrates calls of particular tools available through the NCBI Web service providing requested functionality, while users interactively browse selected records in search GenBank and traverse between NCBI databases using available links. On the other hand, by building macros in the advanced data exploration mode, users create choreographies of eUtils calls, which can lead to the automatic discovery of related data in the specified databases. Conclusions search GenBank extends standard capabilities of the NCBI Entrez search engine in querying biomedical databases. The possibility of creating and saving macros in the search GenBank is a unique feature and has a great potential. The potential will further grow in the future with the increasing density of networks of relationships between data stored in particular databases. search GenBank is available for public use at http://sgb.biotools.pl/. PMID:23452691

search GenBank: interactive orchestration and ad-hoc choreography of Web services in the exploration of the biomedical resources of the National Center For Biotechnology Information.

PubMed

Mrozek, Dariusz; Małysiak-Mrozek, Bożena; Siążnik, Artur

2013-03-01

Due to the growing number of biomedical entries in data repositories of the National Center for Biotechnology Information (NCBI), it is difficult to collect, manage and process all of these entries in one place by third-party software developers without significant investment in hardware and software infrastructure, its maintenance and administration. Web services allow development of software applications that integrate in one place the functionality and processing logic of distributed software components, without integrating the components themselves and without integrating the resources to which they have access. This is achieved by appropriate orchestration or choreography of available Web services and their shared functions. After the successful application of Web services in the business sector, this technology can now be used to build composite software tools that are oriented towards biomedical data processing. We have developed a new tool for efficient and dynamic data exploration in GenBank and other NCBI databases. A dedicated search GenBank system makes use of NCBI Web services and a package of Entrez Programming Utilities (eUtils) in order to provide extended searching capabilities in NCBI data repositories. In search GenBank users can use one of the three exploration paths: simple data searching based on the specified user's query, advanced data searching based on the specified user's query, and advanced data exploration with the use of macros. search GenBank orchestrates calls of particular tools available through the NCBI Web service providing requested functionality, while users interactively browse selected records in search GenBank and traverse between NCBI databases using available links. On the other hand, by building macros in the advanced data exploration mode, users create choreographies of eUtils calls, which can lead to the automatic discovery of related data in the specified databases. search GenBank extends standard capabilities of the NCBI Entrez search engine in querying biomedical databases. The possibility of creating and saving macros in the search GenBank is a unique feature and has a great potential. The potential will further grow in the future with the increasing density of networks of relationships between data stored in particular databases. search GenBank is available for public use at http://sgb.biotools.pl/.

Theory-Led Design of Instruments and Representations in Learning Analytics: Developing a Novel Tool for Orchestration of Online Collaborative Learning

ERIC Educational Resources Information Center

Kelly, Nick; Thompson, Kate; Yeoman, Pippa

2015-01-01

This paper describes theory-led design as a way of developing novel tools for learning analytics (LA). It focuses upon the domain of automated discourse analysis (ADA) of group learning activities to help an instructor to orchestrate online groups in real-time. The paper outlines the literature on the development of LA tools within the domain of…

Spatiotemporal dynamics of Aurora B-PLK1-MCAK signaling axis orchestrates kinetochore bi-orientation and faithful chromosome segregation

PubMed Central

Shao, Hengyi; Huang, Yuejia; Zhang, Liangyu; Yuan, Kai; Chu, Youjun; Dou, Zhen; Jin, Changjiang; Garcia-Barrio, Minerva; Liu, Xing; Yao, Xuebiao

2015-01-01

Chromosome segregation in mitosis is orchestrated by the dynamic interactions between the kinetochore and spindle microtubules. The microtubule depolymerase mitotic centromere-associated kinesin (MCAK) is a key regulator for an accurate kinetochore-microtubule attachment. However, the regulatory mechanism underlying precise MCAK depolymerase activity control during mitosis remains elusive. Here, we describe a novel pathway involving an Aurora B-PLK1 axis for regulation of MCAK activity in mitosis. Aurora B phosphorylates PLK1 on Thr210 to activate its kinase activity at the kinetochores during mitosis. Aurora B-orchestrated PLK1 kinase activity was examined in real-time mitosis using a fluorescence resonance energy transfer-based reporter and quantitative analysis of native PLK1 substrate phosphorylation. Active PLK1, in turn, phosphorylates MCAK at Ser715 which promotes its microtubule depolymerase activity essential for faithful chromosome segregation. Importantly, inhibition of PLK1 kinase activity or expression of a non-phosphorylatable MCAK mutant prevents correct kinetochore-microtubule attachment, resulting in abnormal anaphase with chromosome bridges. We reason that the Aurora B-PLK1 signaling at the kinetochore orchestrates MCAK activity, which is essential for timely correction of aberrant kinetochore attachment to ensure accurate chromosome segregation during mitosis. PMID:26206521

Where Does My Augmented Reality Learning Experience (ARLE) Belong? A Student and Teacher Perspective to Positioning ARLEs

ERIC Educational Resources Information Center

Drljevic, Neven; Wong, Lung Hsiang; Boticki, Ivica

2017-01-01

The paper provides a high-level review of the current state of techno-pedagogical design in Augmented Reality Learning Experiences (ARLEs). The review is based on a rubric constructed from the Meaningful Learning with ICT framework and the Orchestration Load reduction framework, providing, respectively, a view of primarily student- and primarily…

(n-3) Fatty Acids Alleviate Adipose Tissue Inflammation and Insulin Resistance: Mechanistic Insights12

PubMed Central

Kalupahana, Nishan S.; Claycombe, Kate J.; Moustaid-Moussa, Naima

2011-01-01

Obesity is associated with the metabolic syndrome, a significant risk factor for developing type 2 diabetes and cardiovascular diseases. Chronic low-grade inflammation occurring in the adipose tissue of obese individuals is causally linked to the pathogenesis of insulin resistance and the metabolic syndrome. Although the exact trigger of this inflammatory process is unknown, adipose tissue hypoxia, endoplasmic reticular stress, and saturated fatty acid–mediated activation of innate immune processes have been identified as important processes in these disorders. Furthermore, macrophages and T lymphocytes have important roles in orchestrating this immune process. Although energy restriction leading to weight loss is the primary dietary intervention to reverse these obesity-associated metabolic disorders, other interventions targeted at alleviating adipose tissue inflammation have not been explored in detail. In this regard, (n-3) PUFA of marine origin both prevent and reverse high-fat-diet–induced adipose tissue inflammation and insulin resistance in rodents. We provide an update on the pathogenesis of adipose tissue inflammation and insulin resistance in obesity and discuss potential mechanisms by which (n-3) PUFA prevent and reverse these changes and the implications in human health. PMID:22332072

Predictive assimilation framework to support contaminated site understanding and remediation

NASA Astrophysics Data System (ADS)

Versteeg, R. J.; Bianchi, M.; Hubbard, S. S.

2014-12-01

Subsurface system behavior at contaminated sites is driven and controlled by the interplay of physical, chemical, and biological processes occurring at multiple temporal and spatial scales. Effective remediation and monitoring planning requires an understanding of this complexity that is current, predictive (with some level of confidence) and actionable. We present and demonstrate a predictive assimilation framework (PAF). This framework automatically ingests, quality controls and stores near real-time environmental data and processes these data using different inversion and modeling codes to provide information on the current state and evolution of the subsurface system. PAF is implemented as a cloud based software application which has five components: (1) data acquisition, (2) data management, (3) data assimilation and processing, (4) visualization and result deliver and (5) orchestration. Access to and interaction with PAF is done through a standard browser. PAF is designed to be modular so that it can ingest and process different data streams dependent on the site. We will present an implementation of PAF which uses data from a highly instrumented site (the DOE Rifle Subsurface Biogeochemistry Field Observatory in Rifle, Colorado) for which PAF automatically ingests hydrological data and forward models groundwater flow in the saturated zone.

The Schizophrenia Risk Gene MIR137 Acts as a Hippocampal Gene Network Node Orchestrating the Expression of Genes Relevant to Nervous System Development and Function

PubMed Central

Loohuis, Nikkie FM Olde; Kasri, Nael Nadif; Glennon, Jeffrey C; van Bokhoven, Hans; Hébert, Sébastien S; Kaplan, Barry B.; Martens, Gerard JM; Aschrafi, Armaz

2016-01-01

MicroRNAs (miRs) are small regulatory molecules, which orchestrate neuronal development and plasticity through modulation of complex gene networks. microRNA-137 (miR-137) is a brain-enriched RNA with a critical role in regulating brain development and in mediating synaptic plasticity. Importantly, mutations in this miR are associated with the pathoetiology of schizophrenia (SZ), and there is a widespread assumption that disruptions in miR-137 expression lead to aberrant expression of gene regulatory networks associated with SZ. To systematically identify the mRNA targets for this miR, we performed miR-137 gain- and loss-of-function experiments in primary rat hippocampal neurons and profiled differentially expressed mRNAs through next-generation sequencing. We identified 500 genes that were bidirectionally activated or repressed in their expression by the modulation of miR-137 levels. Gene ontology analysis using two independent software resources suggested functions for these miR-137-regulated genes in neurodevelopmental processes, neuronal maturation processes and cell maintenance, all of which known to be critical for proper brain circuitry formation. Since many of the putative miR-137 targets identified here also have been previously shown to be associated with SZ, we propose that this miR acts as a critical gene network hub contributing to the pathophysiology of this neurodevelopmental disorder. PMID:26925706

Molecular events during translocation and proofreading extracted from 200 static structures of DNA polymerase.

PubMed

Ren, Zhong

2016-09-06

DNA polymerases in family B are workhorses of DNA replication that carry out the bulk of the job at a high speed with high accuracy. A polymerase in this family relies on a built-in exonuclease for proofreading. It has not been observed at the atomic resolution how the polymerase advances one nucleotide space on the DNA template strand after a correct nucleotide is incorporated, that is, a process known as translocation. It is even more puzzling how translocation is avoided after the primer strand is excised by the exonuclease and returned back to the polymerase active site once an error occurs. The structural events along the bifurcate pathways of translocation and proofreading have been unwittingly captured by hundreds of structures in Protein Data Bank. This study analyzes all available structures of a representative member in family B and reveals the orchestrated event sequence during translocation and proofreading. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Global changes of the RNA-bound proteome during the maternal-to-zygotic transition in Drosophila

PubMed Central

Sysoev, Vasiliy O.; Fischer, Bernd; Frese, Christian K.; Gupta, Ishaan; Krijgsveld, Jeroen; Hentze, Matthias W.; Castello, Alfredo; Ephrussi, Anne

2016-01-01

The maternal-to-zygotic transition (MZT) is a process that occurs in animal embryos at the earliest developmental stages, during which maternally deposited mRNAs and other molecules are degraded and replaced by products of the zygotic genome. The zygotic genome is not activated immediately upon fertilization, and in the pre-MZT embryo post-transcriptional control by RNA-binding proteins (RBPs) orchestrates the first steps of development. To identify relevant Drosophila RBPs organism-wide, we refined the RNA interactome capture method for comparative analysis of the pre- and post-MZT embryos. We determine 523 proteins as high-confidence RBPs, half of which were not previously reported to bind RNA. Comparison of the RNA interactomes of pre- and post-MZT embryos reveals high dynamicity of the RNA-bound proteome during early development, and suggests active regulation of RNA binding of some RBPs. This resource provides unprecedented insight into the system of RBPs that govern the earliest steps of Drosophila development. PMID:27378189

Dendritic Cells in the Gut: Interaction with Intestinal Helminths

PubMed Central

Mendlovic, Fela; Flisser, Ana

2010-01-01

The mucosal environment in mammals is highly tolerogenic; however, after exposure to pathogens or danger signals, it is able to shift towards an inflammatory response. Dendritic cells (DCs) orchestrate immune responses and are highly responsible, through the secretion of cytokines and expression of surface markers, for the outcome of such immune response. In particular, the DC subsets found in the intestine have specialized functions and interact with different immune as well as nonimmune cells. Intestinal helminths primarily induce Th2 responses where DCs have an important yet not completely understood role. In addition, this cross-talk results in the induction of regulatory T cells (T regs) as a result of the homeostatic mucosal environment. This review highlights the importance of studying the particular relation “helminth-DC-milieu” in view of the significance that each of these factors plays. Elucidating the mechanisms that trigger Th2 responses may provide the understanding of how we might modulate inflammatory processes. PMID:20224759

Continuous and scalable polymer capsule processing for inertial fusion energy target shell fabrication using droplet microfluidics.

PubMed

Li, Jin; Lindley-Start, Jack; Porch, Adrian; Barrow, David

2017-07-24

High specification, polymer capsules, to produce inertial fusion energy targets, were continuously fabricated using surfactant-free, inertial centralisation, and ultrafast polymerisation, in a scalable flow reactor. Laser-driven, inertial confinement fusion depends upon the interaction of high-energy lasers and hydrogen isotopes, contained within small, spherical and concentric target shells, causing a nuclear fusion reaction at ~150 M°C. Potentially, targets will be consumed at ~1 M per day per reactor, demanding a 5000x unit cost reduction to ~$0.20, and is a critical, key challenge. Experimentally, double emulsions were used as templates for capsule-shells, and were formed at 20 Hz, on a fluidic chip. Droplets were centralised in a dynamic flow, and their shapes both evaluated, and mathematically modeled, before subsequent shell solidification. The shells were photo-cured individually, on-the-fly, with precisely-actuated, millisecond-length (70 ms), uniform-intensity UV pulses, delivered through eight, radially orchestrated light-pipes. The near 100% yield rate of uniform shells had a minimum 99.0% concentricity and sphericity, and the solidification processing period was significantly reduced, over conventional batch methods. The data suggest the new possibility of a continuous, on-the-fly, IFE target fabrication process, employing sequential processing operations within a continuous enclosed duct system, which may include cryogenic fuel-filling, and shell curing, to produce ready-to-use IFE targets.

Entry inhibitors: New advances in HCV treatment

PubMed Central

Qian, Xi-Jing; Zhu, Yong-Zhe; Zhao, Ping; Qi, Zhong-Tian

2016-01-01

Hepatitis C virus (HCV) infection affects approximately 3% of the world's population and causes chronic liver diseases, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. Although current antiviral therapy comprising direct-acting antivirals (DAAs) can achieve a quite satisfying sustained virological response (SVR) rate, it is still limited by viral resistance, long treatment duration, combined adverse reactions, and high costs. Moreover, the currently marketed antivirals fail to prevent graft reinfections in HCV patients who receive liver transplantations, probably due to the cell-to-cell transmission of the virus, which is also one of the main reasons behind treatment failure. HCV entry is a highly orchestrated process involving initial attachment and binding, post-binding interactions with host cell factors, internalization, and fusion between the virion and the host cell membrane. Together, these processes provide multiple novel and promising targets for antiviral therapy. Most entry inhibitors target host cell components with high genetic barriers and eliminate viral infection from the very beginning of the viral life cycle. In future, the addition of entry inhibitors to a combination of treatment regimens might optimize and widen the prevention and treatment of HCV infection. This review summarizes the molecular mechanisms and prospects of the current preclinical and clinical development of antiviral agents targeting HCV entry. PMID:26733381

The Good the Bad and the Ugly of Glycosaminoglycans in Tissue Engineering Applications

PubMed Central

Ayerst, Bethanie I.; Merry, Catherine L.R.; Day, Anthony J.

2017-01-01

High sulfation, low cost, and the status of heparin as an already FDA- and EMA- approved product, mean that its inclusion in tissue engineering (TE) strategies is becoming increasingly popular. However, the use of heparin may represent a naïve approach. This is because tissue formation is a highly orchestrated process, involving the temporal expression of numerous growth factors and complex signaling networks. While heparin may enhance the retention and activity of certain growth factors under particular conditions, its binding ‘promiscuity’ means that it may also inhibit other factors that, for example, play an important role in tissue maintenance and repair. Within this review we focus on articular cartilage, highlighting the complexities and highly regulated processes that are involved in its formation, and the challenges that exist in trying to effectively engineer this tissue. Here we discuss the opportunities that glycosaminoglycans (GAGs) may provide in advancing this important area of regenerative medicine, placing emphasis on the need to move away from the common use of heparin, and instead focus research towards the utility of specific GAG preparations that are able to modulate the activity of growth factors in a more controlled and defined manner, with less off-target effects. PMID:28608822

GITEWS, an extensible and open integration platform for manifold sensor systems and processing components based on Sensor Web Enablement and the principles of Service Oriented Architectures

NASA Astrophysics Data System (ADS)

Haener, Rainer; Waechter, Joachim; Fleischer, Jens; Herrnkind, Stefan; Schwarting, Herrmann

2010-05-01

The German Indonesian Tsunami Early Warning System (GITEWS) is a multifaceted system consisting of various sensor types like seismometers, sea level sensors or GPS stations, and processing components, all with their own system behavior and proprietary data structure. To operate a warning chain, beginning from measurements scaling up to warning products, all components have to interact in a correct way, both syntactically and semantically. Designing the system great emphasis was laid on conformity to the Sensor Web Enablement (SWE) specification by the Open Geospatial Consortium (OGC). The technical infrastructure, the so called Tsunami Service Bus (TSB) follows the blueprint of Service Oriented Architectures (SOA). The TSB is an integration concept (SWE) where functionality (observe, task, notify, alert, and process) is grouped around business processes (Monitoring, Decision Support, Sensor Management) and packaged as interoperable services (SAS, SOS, SPS, WNS). The benefits of using a flexible architecture together with SWE lead to an open integration platform: • accessing and controlling heterogeneous sensors in a uniform way (Functional Integration) • assigns functionality to distinct services (Separation of Concerns) • allows resilient relationship between systems (Loose Coupling) • integrates services so that they can be accessed from everywhere (Location Transparency) • enables infrastructures which integrate heterogeneous applications (Encapsulation) • allows combination of services (Orchestration) and data exchange within business processes Warning systems will evolve over time: New sensor types might be added, old sensors will be replaced and processing components will be improved. From a collection of few basic services it shall be possible to compose more complex functionality essential for specific warning systems. Given these requirements a flexible infrastructure is a prerequisite for sustainable systems and their architecture must be tailored for evolution. The use of well-known techniques and widely used open source software implementing industrial standards reduces the impact of service modifications allowing the evolution of a system as a whole. GITEWS implemented a solution to feed sensor raw data from any (remote) system into the infrastructure. Specific dispatchers enable plugging in sensor-type specific processing without changing the architecture. Client components don't need to be adjusted if new sensor-types or individuals are added to the system, because they access them via standardized services. One of the outstanding features of service-oriented architectures is the possibility to compose new services from existing ones. The so called orchestration, allows the definition of new warning processes which can be adapted easily to new requirements. This approach has following advantages: • With implementing SWE it is possible to establish the "detection" and integration of sensors via the internet. Thus a system of systems combining early warning functionality at different levels of detail is feasible. • Any institution could add both its own components as well as components from third parties if they are developed in conformance to SOA principles. In a federation an institution keeps the ownership of its data and decides which data are provided by a service and when. • A system can be deployed at minor costs as a core for own development at any institution and thus enabling autonomous early warning- or monitoring systems. The presentation covers both design and various instantiations (live demonstration) of the GITEWS architecture. Experiences concerning the design and complexity of SWE will be addressed in detail. A substantial amount of attention is laid on the techniques and methods of extending the architecture, adapting proprietary components to SWE services and encoding, and their orchestration in high level workflows and processes. Furthermore the potential of the architecture concerning adaptive behavior, collaboration across boundaries and semantic interoperability will be addressed.

Orchestrating high-throughput genomic analysis with Bioconductor

PubMed Central

Huber, Wolfgang; Carey, Vincent J.; Gentleman, Robert; Anders, Simon; Carlson, Marc; Carvalho, Benilton S.; Bravo, Hector Corrada; Davis, Sean; Gatto, Laurent; Girke, Thomas; Gottardo, Raphael; Hahne, Florian; Hansen, Kasper D.; Irizarry, Rafael A.; Lawrence, Michael; Love, Michael I.; MacDonald, James; Obenchain, Valerie; Oleś, Andrzej K.; Pagès, Hervé; Reyes, Alejandro; Shannon, Paul; Smyth, Gordon K.; Tenenbaum, Dan; Waldron, Levi; Morgan, Martin

2015-01-01

Bioconductor is an open-source, open-development software project for the analysis and comprehension of high-throughput data in genomics and molecular biology. The project aims to enable interdisciplinary research, collaboration and rapid development of scientific software. Based on the statistical programming language R, Bioconductor comprises 934 interoperable packages contributed by a large, diverse community of scientists. Packages cover a range of bioinformatic and statistical applications. They undergo formal initial review and continuous automated testing. We present an overview for prospective users and contributors. PMID:25633503

German Day: A Practical Guide to Connecting High School and Post-Secondary Programs

ERIC Educational Resources Information Center

Howards, Alyssa; Rinner, Susanne; Gulewich, Beth

2018-01-01

An annual German Day event can be a powerful tool to motivate students, increase visibility of state and local German programs, and, ultimately, boost enrollments. However, it can also be a daunting undertaking that is often orchestrated by a single person. This article offers a user guide that can help others plan their own German Day, be it a…

The Swarm Archiving Payload Data Facility, an Instance Configuration of the ESA Multi-Mission Facility

NASA Astrophysics Data System (ADS)

Pruin, B.; Martini, A.; Shanmugam, P.; Lopes, C.

2015-04-01

The Swarm mission consists of 3 satellites, each carrying an identical set of instruments. The scientific algorithms for processing are organized in 11 separate processing steps including automated product quality control. In total, the mission data consists of data products of several hundred distinct types from raw to level 2 product types and auxiliary data. The systematic production for Swarm within the ESA Archiving and Payload Data Facility (APDF) is performed up to level 2. The production up to L2 (CAT2-mature algorithm) is performed completely within the APDF. A separate systematic production chain from L1B to L2 (CAT1-evolving algorithm) is performed by an external facility (L2PS) with output files archived within the APDF as well. The APDF also performs re-processing exercises. Re-processing may start directly from the acquired data or from any other intermediate level resulting in the need for a refined product version and baseline management. Storage, dissemination and circulation functionality is configurable in the ESA generic multi-mission elements and does not require any software coding. The control of the production is more involved. While the interface towards the algorithmic entities is standardized due to the introduction of a generic IPF interface by ESA, the orchestration of the individual IPFs into the overall workflows is distinctly mission-specific and not as amenable to standardization. The ESA MMFI production management system provides extension points to integrate additional logical elements for the build-up of complex orchestrated workflows. These extension points have been used to inject the Swarm-specific production logic into the system. A noteworthy fact about the APDF is that the dissemination elements are hosted in a high bandwidth infrastructure procured as a managed service, thus affording users a considerable access bandwidth. This paper gives an overview of the Swarm APDF data flows. It describes the elements of the solution with particular focus on how the available generic multi-mission functionality of the ESA MMFI was utilized and where there was a need to implement missionspecific extensions and plug-ins. The paper concludes with some statistics on the system output during commissioning and early operational phases as well as some general considerations on the utilization of a framework like the ESA MMFI, discussing benefits and pitfalls of the approach.

Genomic control of patterning

PubMed Central

Peter, Isabelle S.; Davidson, Eric H.

2014-01-01

The development of multicellular organisms involves the partitioning of the organism into territories of cells of specific structure and function. The information for spatial patterning processes is directly encoded in the genome. The genome determines its own usage depending on stage and position, by means of interactions that constitute gene regulatory networks (GRNs). The GRN driving endomesoderm development in sea urchin embryos illustrates different regulatory strategies by which developmental programs are initiated, orchestrated, stabilized or excluded to define the pattern of specified territories in the developing embryo. PMID:19378258

The role of the ubiquitin proteasome system in the memory process.

PubMed

Lip, Philomena Z Y; Demasi, Marilene; Bonatto, Diego

2017-01-01

Quite intuitive is the notion that memory formation and consolidation is orchestrated by protein synthesis because of the synaptic plasticity necessary for those processes. Nevertheless, recent advances have begun accumulating evidences of a high requirement for protein degradation on the molecular mechanisms of the memory process in the mammalian brain. Because degradation determines protein half-life, degradation has been increasingly recognized as an important intracellular regulatory mechanism. The proteasome is the main player in the degradation of intracellular proteins. Proteasomal substrates are mainly degraded after a post-translational modification by a poly-ubiquitin chain. Latter process, namely poly-ubiquitination, is highly regulated at the step of the ubiquitin molecule transferring to the protein substrate mediated by a set of proteins whose genes represent almost 2% of the human genome. Understanding the role of polyubiquitin-mediated protein degradation has challenging researchers in many fields of investigation as a new source of targets for therapeutic intervention, e.g. E3 ligases that transfer ubiquitin moieties to the substrate. The goal of present work was to uncover mechanisms underlying memory processes regarding the role of the ubiquitin-proteasome system (UPS). For that purpose, preceded of a short review on UPS and memory processes a top-down systems biology approach was applied to establish central proteins involved in memory formation and consolidation highlighting their cross-talking with the UPS. According to that approach, the pattern of expression of several elements of the UPS were found overexpressed in regions of the brain involved in processing cortical inputs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Spectraplakins: Master orchestrators of cytoskeletal dynamics

PubMed Central

Suozzi, Kathleen C.; Wu, Xiaoyang

2012-01-01

The dynamics of different cytoskeletal networks are coordinated to bring about many fundamental cellular processes, from neuronal pathfinding to cell division. Increasing evidence points to the importance of spectraplakins in integrating cytoskeletal networks. Spectraplakins are evolutionarily conserved giant cytoskeletal cross-linkers, which belong to the spectrin superfamily. Their genes consist of multiple promoters and many exons, yielding a vast array of differential splice forms with distinct functions. Spectraplakins are also unique in their ability to associate with all three elements of the cytoskeleton: F-actin, microtubules, and intermediate filaments. Recent studies have begun to unveil their role in a wide range of processes, from cell migration to tissue integrity. PMID:22584905

MicroRNA in Metabolic Re-Programming and Their Role in Tumorigenesis

PubMed Central

Tomasetti, Marco; Amati, Monica; Santarelli, Lory; Neuzil, Jiri

2016-01-01

The process of metabolic re-programing is linked to the activation of oncogenes and/or suppression of tumour suppressor genes, which are regulated by microRNAs (miRNAs). The interplay between oncogenic transformation-driven metabolic re-programming and modulation of aberrant miRNAs further established their critical role in the initiation, promotion and progression of cancer by creating a tumorigenesis-prone microenvironment, thus orchestrating processes of evasion to apoptosis, angiogenesis and invasion/migration, as well metastasis. Given the involvement of miRNAs in tumour development and their global deregulation, they may be perceived as biomarkers in cancer of therapeutic relevance. PMID:27213336

From cells to tissue: A continuum model of epithelial mechanics

NASA Astrophysics Data System (ADS)

Ishihara, Shuji; Marcq, Philippe; Sugimura, Kaoru

2017-08-01

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

Neuroimaging the interaction of mind and metabolism in humans

PubMed Central

D’Agostino, Alexandra E.; Small, Dana M.

2012-01-01

Hormonal and metabolic signals interact with neural circuits orchestrating behavior to guide food intake. Neuroimaging techniques such as functional magnetic resonance imaging (fMRI) enable the identification of where in the brain particular mental processes like desire, satiety and pleasure occur. Once these neural circuits are described it then becomes possible to determine how metabolic and hormonal signals can alter brain response to influence psychological states and decision-making processes to guide intake. Here, we provide an overview of the contributions of functional neuroimaging to the understanding of how subjective and neural responses to food and food cues interact with metabolic/hormonal factors. PMID:24024114

OpenLMD, multimodal monitoring and control of LMD processing

NASA Astrophysics Data System (ADS)

Rodríguez-Araújo, Jorge; García-Díaz, Antón

2017-02-01

This paper presents OpenLMD, a novel open-source solution for on-line multimodal monitoring of Laser Metal Deposition (LMD). The solution is also applicable to a wider range of laser-based applications that require on-line control (e.g. laser welding). OpenLMD is a middleware that enables the orchestration and virtualization of a LMD robot cell, using several open-source frameworks (e.g. ROS, OpenCV, PCL). The solution also allows reconfiguration by easy integration of multiple sensors and processing equipment. As a result, OpenLMD delivers significant advantages over existing monitoring and control approaches, such as improved scalability, and multimodal monitoring and data sharing capabilities.

Deep conservation of cis-regulatory elements in metazoans

PubMed Central

Maeso, Ignacio; Irimia, Manuel; Tena, Juan J.; Casares, Fernando; Gómez-Skarmeta, José Luis

2013-01-01

Despite the vast morphological variation observed across phyla, animals share multiple basic developmental processes orchestrated by a common ancestral gene toolkit. These genes interact with each other building complex gene regulatory networks (GRNs), which are encoded in the genome by cis-regulatory elements (CREs) that serve as computational units of the network. Although GRN subcircuits involved in ancient developmental processes are expected to be at least partially conserved, identification of CREs that are conserved across phyla has remained elusive. Here, we review recent studies that revealed such deeply conserved CREs do exist, discuss the difficulties associated with their identification and describe new approaches that will facilitate this search. PMID:24218633

Creating a halo traction wheelchair resource manual: using the EBP approach.

PubMed

Difazio, Rachel

2003-04-01

This article describes a clinically based project that used evidence-based practice (EBP). It follows the EBP process of: (1) identifying a clinical problem and stating a clinical question that focuses the process; (2) doing a literature search for best research evidence; (3) using query techniques, such as phone calls and e-mails, to determine best clinical practice among similar institutions; and (4) drawing a practice conclusion-to accept the status quo, to instigate change of practice, or to do more research. This project was an interdisciplinary effort orchestrated by the surgical programs nurses at Boston Children's Hospital. Copyright 2003, Elsevier Inc. All rights reserved.

Evolving marine biomimetics for regenerative dentistry.

PubMed

Green, David W; Lai, Wing-Fu; Jung, Han-Sung

2014-05-13

New products that help make human tissue and organ regeneration more effective are in high demand and include materials, structures and substrates that drive cell-to-tissue transformations, orchestrate anatomical assembly and tissue integration with biology. Marine organisms are exemplary bioresources that have extensive possibilities in supporting and facilitating development of human tissue substitutes. Such organisms represent a deep and diverse reserve of materials, substrates and structures that can facilitate tissue reconstruction within lab-based cultures. The reason is that they possess sophisticated structures, architectures and biomaterial designs that are still difficult to replicate using synthetic processes, so far. These products offer tantalizing pre-made options that are versatile, adaptable and have many functions for current tissue engineers seeking fresh solutions to the deficiencies in existing dental biomaterials, which lack the intrinsic elements of biofunctioning, structural and mechanical design to regenerate anatomically correct dental tissues both in the culture dish and in vivo.

Evolving Marine Biomimetics for Regenerative Dentistry

PubMed Central

Green, David W.; Lai, Wing-Fu; Jung, Han-Sung

2014-01-01

New products that help make human tissue and organ regeneration more effective are in high demand and include materials, structures and substrates that drive cell-to-tissue transformations, orchestrate anatomical assembly and tissue integration with biology. Marine organisms are exemplary bioresources that have extensive possibilities in supporting and facilitating development of human tissue substitutes. Such organisms represent a deep and diverse reserve of materials, substrates and structures that can facilitate tissue reconstruction within lab-based cultures. The reason is that they possess sophisticated structures, architectures and biomaterial designs that are still difficult to replicate using synthetic processes, so far. These products offer tantalizing pre-made options that are versatile, adaptable and have many functions for current tissue engineers seeking fresh solutions to the deficiencies in existing dental biomaterials, which lack the intrinsic elements of biofunctioning, structural and mechanical design to regenerate anatomically correct dental tissues both in the culture dish and in vivo. PMID:24828293

Fibroblast growth factors: key players in regeneration and tissue repair.

PubMed

Maddaluno, Luigi; Urwyler, Corinne; Werner, Sabine

2017-11-15

Tissue injury initiates a complex repair process, which in some organisms can lead to the complete regeneration of a tissue. In mammals, however, the repair of most organs is imperfect and results in scar formation. Both regeneration and repair are orchestrated by a highly coordinated interplay of different growth factors and cytokines. Among the key players are the fibroblast growth factors (FGFs), which control the migration, proliferation, differentiation and survival of different cell types. In addition, FGFs influence the expression of other factors involved in the regenerative response. Here, we summarize current knowledge on the roles of endogenous FGFs in regeneration and repair in different organisms and in different tissues and organs. Gaining a better understanding of these FGF activities is important for appropriate modulation of FGF signaling after injury to prevent impaired healing and to promote organ regeneration in humans. © 2017. Published by The Company of Biologists Ltd.

ICDA: A Platform for Intelligent Care Delivery Analytics

PubMed Central

Gotz, David; Stavropoulos, Harry; Sun, Jimeng; Wang, Fei

2012-01-01

The identification of high-risk patients is a critical component in improving patient outcomes and managing costs. This paper describes the Intelligent Care Delivery Analytics platform (ICDA), a system which enables risk assessment analytics that process large collections of dynamic electronic medical data to identify at-risk patients. ICDA works by ingesting large volumes of data into a common data model, then orchestrating a collection of analytics that identify at-risk patients. It also provides an interactive environment through which users can access and review the analytics results. In addition, ICDA provides APIs via which analytics results can be retrieved to surface in external applications. A detailed review of ICDA’s architecture is provided. Descriptions of four use cases are included to illustrate ICDA’s application within two different data environments. These use cases showcase the system’s flexibility and exemplify the types of analytics it enables. PMID:23304296

Transforming growth factor β family members in regulation of vascular function: in the light of vascular conditional knockouts.

PubMed

Jakobsson, Lars; van Meeteren, Laurens A

2013-05-15

Blood vessels are composed of endothelial cells, mural cells (smooth muscle cells and pericytes) and their shared basement membrane. During embryonic development a multitude of signaling components orchestrate the formation of new vessels. The process is highly dependent on correct dosage, spacing and timing of these signaling molecules. As vessels mature some cascades remain active, albeit at very low levels, and may be reactivated upon demand. Members of the Transforming growth factor β (TGF-β) protein family are strongly engaged in developmental angiogenesis but are also regulators of vascular integrity in the adult. In humans various genetic alterations within this protein family cause vascular disorders, involving disintegration of vascular integrity. Here we summarize and discuss recent data gathered from conditional and endothelial cell specific genetic loss-of-function of members of the TGF-β family in the mouse. Copyright © 2013 Elsevier Inc. All rights reserved.

Orchestrating Distributed Resource Ensembles for Petascale Science

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

Baldin, Ilya; Mandal, Anirban; Ruth, Paul

2014-04-24

Distributed, data-intensive computational science applications of interest to DOE scientific com- munities move large amounts of data for experiment data management, distributed analysis steps, remote visualization, and accessing scientific instruments. These applications need to orchestrate ensembles of resources from multiple resource pools and interconnect them with high-capacity multi- layered networks across multiple domains. It is highly desirable that mechanisms are designed that provide this type of resource provisioning capability to a broad class of applications. It is also important to have coherent monitoring capabilities for such complex distributed environments. In this project, we addressed these problems by designing an abstractmore » API, enabled by novel semantic resource descriptions, for provisioning complex and heterogeneous resources from multiple providers using their native provisioning mechanisms and control planes: computational, storage, and multi-layered high-speed network domains. We used an extensible resource representation based on semantic web technologies to afford maximum flexibility to applications in specifying their needs. We evaluated the effectiveness of provisioning using representative data-intensive ap- plications. We also developed mechanisms for providing feedback about resource performance to the application, to enable closed-loop feedback control and dynamic adjustments to resource allo- cations (elasticity). This was enabled through development of a novel persistent query framework that consumes disparate sources of monitoring data, including perfSONAR, and provides scalable distribution of asynchronous notifications.« less

Stem cell-dependent formation of a functional anterior regeneration pole in planarians requires Zic and Forkhead transcription factors.

PubMed

Vogg, Matthias C; Owlarn, Suthira; Pérez Rico, Yuvia A; Xie, Jianlei; Suzuki, Yoko; Gentile, Luca; Wu, Wei; Bartscherer, Kerstin

2014-06-15

Planarians can regenerate their head within days. This process depends on the direction of adult stem cells to wound sites and the orchestration of their progenitors to commit to appropriate lineages and to arrange into patterned tissues. We identified a zinc finger transcription factor, Smed-ZicA, as a downstream target of Smed-FoxD, a Forkhead transcription factor required for head regeneration. Smed-zicA and Smed-FoxD are co-expressed with the Wnt inhibitor notum and the Activin inhibitor follistatin in a cluster of cells at the anterior-most tip of the regenerating head - the anterior regeneration pole - and in surrounding stem cell progeny. Depletion of Smed-zicA and Smed-FoxD by RNAi abolishes notum and follistatin expression at the pole and inhibits head formation downstream of initial polarity decisions. We suggest a model in which ZicA and FoxD transcription factors synergize to control the formation of Notum- and Follistatin-producing anterior pole cells. Pole formation might constitute an early step in regeneration, resulting in a signaling center that orchestrates cellular events in the growing tissue. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

A blueprint for computational analysis of acoustical scattering from orchestral panel arrays

NASA Astrophysics Data System (ADS)

Burns, Thomas

2005-09-01

Orchestral panel arrays have been a topic of interest to acousticians, and it is reasonable to expect optimal design criteria to result from a combination of musician surveys, on-stage empirical data, and computational modeling of various configurations. Preparing a musicians survey to identify specific mechanisms of perception and sound quality is best suited for a clinically experienced hearing scientist. Measuring acoustical scattering from a panel array and discerning the effects from various boundaries is best suited for the experienced researcher in engineering acoustics. Analyzing a numerical model of the panel arrays is best suited for the tools typically used in computational engineering analysis. Toward this end, a streamlined process will be described using PROENGINEER to define a panel array geometry in 3-D, a commercial mesher to numerically discretize this geometry, SYSNOISE to solve the associated boundary element integral equations, and MATLAB to visualize the results. The model was run (background priority) on an SGI Altix (Linux) server with 12 CPUs, 24 Gbytes of RAM, and 1 Tbyte of disk space. These computational resources are available to research teams interested in this topic and willing to write and pursue grants.

The nucleosome: orchestrating DNA damage signaling and repair within chromatin.

PubMed

Agarwal, Poonam; Miller, Kyle M

2016-10-01

DNA damage occurs within the chromatin environment, which ultimately participates in regulating DNA damage response (DDR) pathways and repair of the lesion. DNA damage activates a cascade of signaling events that extensively modulates chromatin structure and organization to coordinate DDR factor recruitment to the break and repair, whilst also promoting the maintenance of normal chromatin functions within the damaged region. For example, DDR pathways must avoid conflicts between other DNA-based processes that function within the context of chromatin, including transcription and replication. The molecular mechanisms governing the recognition, target specificity, and recruitment of DDR factors and enzymes to the fundamental repeating unit of chromatin, i.e., the nucleosome, are poorly understood. Here we present our current view of how chromatin recognition by DDR factors is achieved at the level of the nucleosome. Emerging evidence suggests that the nucleosome surface, including the nucleosome acidic patch, promotes the binding and activity of several DNA damage factors on chromatin. Thus, in addition to interactions with damaged DNA and histone modifications, nucleosome recognition by DDR factors plays a key role in orchestrating the requisite chromatin response to maintain both genome and epigenome integrity.

Lung Epithelial Cells Coordinate Innate Lymphocytes and Immunity against Pulmonary Fungal Infection.

PubMed

Hernández-Santos, Nydiaris; Wiesner, Darin L; Fites, J Scott; McDermott, Andrew J; Warner, Thomas; Wüthrich, Marcel; Klein, Bruce S

2018-04-11

Lung epithelial cells (LECs) are strategically positioned in the airway mucosa to provide barrier defense. LECs also express pattern recognition receptors and a myriad of immune genes, but their role in immunity is often concealed by the activities of "professional" immune cells, particularly in the context of fungal infection. Here, we demonstrate that NF-κB signaling in LECs is essential for immunity against the pulmonary fungal pathogen Blastomyces dermatitidis. LECs orchestrate innate antifungal immunity by augmenting the numbers of interleukin-17A (IL-17A)- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing innate lymphocytes, specifically "natural" Th17 (nTh17) cells. Innate lymphocyte-derived IL-17A and GM-CSF in turn enable phagocyte-driven fungal killing. LECs regulate the numbers of nTh17 cells via the production of chemokines such as CCL20, a process dependent on IL-1α-IL-1 receptor (IL-1R) signaling on LECs. Therefore, LECs orchestrate IL-17A- and GM-CSF-mediated immunity in an IL-1R-dependent manner and represent an essential component of innate immunity to pulmonary fungal pathogens. Copyright © 2018 Elsevier Inc. All rights reserved.

The SEEKING mind: primal neuro-affective substrates for appetitive incentive states and their pathological dynamics in addictions and depression.

PubMed

Alcaro, Antonio; Panksepp, Jaak

2011-10-01

Appetitive motivation and incentive states are essential functions sustained by a common emotional brain process, the SEEKING disposition, which drives explorative and approach behaviors, sustains goal-directed activity, promotes anticipatory cognitions, and evokes feelings of positive excitement which control reward-learning. All such functions are orchestrated by the same "archetypical" neural processes, activated in ancient subcortical areas and transported to the forebrain by the mesolimbic dopamine (ML-DA) system. In mammals, the neurophysiology of the SEEKING urge is expressed by DA-promoted high-frequency oscillations, in the form of transient and synchronized gamma waves (>30Hz) emerging in limbic forebrain and diffusing throughout basal ganglia-thalamocortical (BG-T-C) circuits. These patterns may be considered basic "SEEKING neurodynamic impulses" which represent the primary-process exploratory disposition getting integrated with information relative to the external and the internal environment. Abnormal manifestation of SEEKING and its neural substrates are evident in clinical depression and addiction. Specifically, depression is characterized by reduced recruitment of SEEKING, while addictions reflect re-organizations of the SEEKING disposition around ultra-specific appetitive memories and compulsive activities. Copyright © 2011 Elsevier Ltd. All rights reserved.

Organizational culture: the critical link between strategy and results.

PubMed

Vestal, K W; Fralicx, R D; Spreier, S W

1997-01-01

The U.S. Department of Veterans Affairs (VA) is undertaking a massive reorganization to transform itself into a more efficient, patient-focused healthcare system. It has developed a new strategy and structure. But if it is to achieve the rapid, sustainable transformation needed to succeed in today's environment, it must also change its culture. The rigid, functionally focused, command-and-control culture that has long been a hallmark of VA must be replaced by one that values speed, flexibility, and the processes for delivering high-quality, cost-effective patient care. Such a change will not come easily. In addition to the normal hurdles, several barriers are unique to VA. They include ingrained bureaucratic traditions and behaviors, constraints imposed by the federal government, close scrutiny by powerful service organizations, and a Civil Service employee base that makes the hiring, promoting, and removing of employees a slow, unwieldy, and procedurally complex exercise. In a climate that does not encourage change, successful transformation must be well orchestrated. To drive the change, the leadership must be mobilized as a team, new work processes must be developed, and a full range of human resource processes must be established.

Orchestration: The Movement and Vocal Behavior of Free-Ranging Norwegian Killer Whales (Orcinus Orca)

DTIC Science & Technology

2008-06-01

MIT/WHOI 2008-08 Massachusetts Institute of Technology Woods Hole Oceanographic Institution 0" joint Program in Oceanography/ 0 OFTtcy Applied Ocean...Biology Paola Malanotte-Rizzoli James A. Yoder MIT Director of Joint Program WHOI Dean of Graduate Studies ORCHESTRATION: THE MOVEMENT AND VOCAL BEHAVIOR...Steve Young and Syd Lewis, have mentored and believed in me, a gift that I cherish. Stacy DeRuiter and I have been labmates since we began the Joint

[Fibroblast growth factors and their effects in pancreas organogenesis].

PubMed

Gnatenko, D A; Kopantzev, E P; Sverdlov, E D

2017-05-01

Fibroblast growth factors (FGF) - growth factors that regulate many important biological processes, including proliferation and differentiation of embryonic cells during organogenesis. In this review, we will summarize current information about the involvement of FGFs in the pancreas organogenesis. Pancreas organogenesis is a complex process, which involves constant signaling from mesenchymal tissue. This orchestrates the activation of various regulator genes at specific stages, determining the specification of progenitor cells. Alterations in FGF/FGFR signaling pathway during this process lead to incorrect activation of the master genes, which leads to different pathologies during pancreas development. Understanding the full picture about role of FGF factors in pancreas development will make it possible to more accurately understand their role in other pathologies of this organ, including carcinogenesis.

Drug delivery systems and materials for wound healing applications.

PubMed

Saghazadeh, Saghi; Rinoldi, Chiara; Schot, Maik; Kashaf, Sara Saheb; Sharifi, Fatemeh; Jalilian, Elmira; Nuutila, Kristo; Giatsidis, Giorgio; Mostafalu, Pooria; Derakhshandeh, Hossein; Yue, Kan; Swieszkowski, Wojciech; Memic, Adnan; Tamayol, Ali; Khademhosseini, Ali

2018-04-05

Chronic, non-healing wounds place a significant burden on patients and healthcare systems, resulting in impaired mobility, limb amputation, or even death. Chronic wounds result from a disruption in the highly orchestrated cascade of events involved in wound closure. Significant advances in our understanding of the pathophysiology of chronic wounds have resulted in the development of drugs designed to target different aspects of the impaired processes. However, the hostility of the wound environment rich in degradative enzymes and its elevated pH, combined with differences in the time scales of different physiological processes involved in tissue regeneration require the use of effective drug delivery systems. In this review, we will first discuss the pathophysiology of chronic wounds and then the materials used for engineering drug delivery systems. Different passive and active drug delivery systems used in wound care will be reviewed. In addition, the architecture of the delivery platform and its ability to modulate drug delivery are discussed. Emerging technologies and the opportunities for engineering more effective wound care devices are also highlighted. Copyright © 2018 Elsevier B.V. All rights reserved.

A Parallel Distributed-Memory Particle Method Enables Acquisition-Rate Segmentation of Large Fluorescence Microscopy Images

PubMed Central

Afshar, Yaser; Sbalzarini, Ivo F.

2016-01-01

Modern fluorescence microscopy modalities, such as light-sheet microscopy, are capable of acquiring large three-dimensional images at high data rate. This creates a bottleneck in computational processing and analysis of the acquired images, as the rate of acquisition outpaces the speed of processing. Moreover, images can be so large that they do not fit the main memory of a single computer. We address both issues by developing a distributed parallel algorithm for segmentation of large fluorescence microscopy images. The method is based on the versatile Discrete Region Competition algorithm, which has previously proven useful in microscopy image segmentation. The present distributed implementation decomposes the input image into smaller sub-images that are distributed across multiple computers. Using network communication, the computers orchestrate the collectively solving of the global segmentation problem. This not only enables segmentation of large images (we test images of up to 1010 pixels), but also accelerates segmentation to match the time scale of image acquisition. Such acquisition-rate image segmentation is a prerequisite for the smart microscopes of the future and enables online data compression and interactive experiments. PMID:27046144

A Parallel Distributed-Memory Particle Method Enables Acquisition-Rate Segmentation of Large Fluorescence Microscopy Images.

PubMed

Afshar, Yaser; Sbalzarini, Ivo F

2016-01-01

Modern fluorescence microscopy modalities, such as light-sheet microscopy, are capable of acquiring large three-dimensional images at high data rate. This creates a bottleneck in computational processing and analysis of the acquired images, as the rate of acquisition outpaces the speed of processing. Moreover, images can be so large that they do not fit the main memory of a single computer. We address both issues by developing a distributed parallel algorithm for segmentation of large fluorescence microscopy images. The method is based on the versatile Discrete Region Competition algorithm, which has previously proven useful in microscopy image segmentation. The present distributed implementation decomposes the input image into smaller sub-images that are distributed across multiple computers. Using network communication, the computers orchestrate the collectively solving of the global segmentation problem. This not only enables segmentation of large images (we test images of up to 10(10) pixels), but also accelerates segmentation to match the time scale of image acquisition. Such acquisition-rate image segmentation is a prerequisite for the smart microscopes of the future and enables online data compression and interactive experiments.

Determining the Value of Future Information

DTIC Science & Technology

2011-03-01

trouble spots around the world, help plan military operations, and monitor the environment. The NRO’s Operational Support Office ( OSO ) “orchestrates...offices” (Parnell, Bennet, Engelbrecht, Szafranski, 2002:77). Parnell’s team’s research was intended “to help the OSO to identify and develop high- value...tasks that directly support OSO and NRO strategic objectives and to select the best portfolio of tasks to meet resource and programmatic constraints

Toll-like receptor 4 orchestrates neutrophil recruitment into airways during the first hours of Bordetella pertussis infection.

PubMed

Moreno, Griselda; Errea, Agustina; Van Maele, Laurye; Roberts, Roy; Léger, Hélène; Sirard, Jean Claude; Benecke, Arndt; Rumbo, Martin; Hozbor, Daniela

2013-01-01

Most of the knowledge on the impact of Bordetella pertussis lipo-oligosaccharide (LOS) on the infectious process was obtained when the bacteria was established within the host. The aim of the present work was to determine the role of TLR4 at a very early step of the infectious process. To this end we used a transcriptomic approach on B. pertussis intranasal infection model in C3H/HeN, a TLR4-competent mouse strain, and C3H/HeJ, a TLR4-deficient mouse strain. The expression of approximately 140 genes was significantly changed 2 h post-infection in the C3H/HeN animals compared to the C3H/HeJ animals, which were essentially non-responders at this early time point. Pathways specific for immunity and defense, chemokine- and cytokine-mediated functions and TLR signaling, were activated upon infection in the TLR4 competent mice either at 2 h or 24 h. Furthermore, we observed that TLR4 signaling is absolutely required to promote the rapid recruitment of neutrophils into the airways. Interestingly, the depletion of those neutrophils impacted on B. pertussis lung counts in the first three days, thereby exacerbating the lung infection. In summary, we determined that TLR4 is a central player in initial neutrophil recruitment and orchestration of the very early innate defense against B. pertussis. Copyright © 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

South Africa: a legacy of family disruption.

PubMed

Budlender, Debbie; Lund, Francie

2011-01-01

This article draws together unusual characteristics of the legacy of apartheid in South Africa: the state-orchestrated destruction of family life, high rates of unemployment and a high prevalence of HIV/AIDS. The disruption of family life has resulted in a situation in which many women have to fulfil the role of both breadwinner and care giver in a context of high unemployment and very limited economic opportunities. The question that follows is: given this crisis of care, to what extent can or will social protection and employment-related social policies provide the support women and children need?

Strategic role of the ubiquitin-dependent segregase p97 (VCP or Cdc48) in DNA replication.

PubMed

Ramadan, Kristijan; Halder, Swagata; Wiseman, Katherine; Vaz, Bruno

2017-02-01

Genome amplification (DNA synthesis) is one of the most demanding cellular processes in all proliferative cells. The DNA replication machinery (also known as the replisome) orchestrates genome amplification during S-phase of the cell cycle. Genetic material is particularly vulnerable to various events that can challenge the replisome during its assembly, activation (firing), progression (elongation) and disassembly from chromatin (termination). Any disturbance of the replisome leads to stalling of the DNA replication fork and firing of dormant replication origins, a process known as DNA replication stress. DNA replication stress is considered to be one of the main causes of sporadic cancers and other pathologies related to tissue degeneration and ageing. The mechanisms of replisome assembly and elongation during DNA synthesis are well understood. However, once DNA synthesis is complete, the process of replisome disassembly, and its removal from chromatin, remains unclear. In recent years, a growing body of evidence has alluded to a central role in replisome regulation for the ubiquitin-dependent protein segregase p97, also known as valosin-containing protein (VCP) in metazoans and Cdc48 in lower eukaryotes. By orchestrating the spatiotemporal turnover of the replisome, p97 plays an essential role in DNA replication. In this review, we will summarise our current knowledge about how p97 controls the replisome from replication initiation, to elongation and finally termination. We will also further examine the more recent findings concerning the role of p97 and how mutations in p97 cofactors, also known as adaptors, cause DNA replication stress induced genomic instability that leads to cancer and accelerated ageing. To our knowledge, this is the first comprehensive review concerning the mechanisms involved in the regulation of DNA replication by p97.

Mutations in ATRX, encoding a SWI/SNF-like protein, cause diverse changes in the pattern of DNA methylation.

PubMed

Gibbons, R J; McDowell, T L; Raman, S; O'Rourke, D M; Garrick, D; Ayyub, H; Higgs, D R

2000-04-01

A goal of molecular genetics is to understand the relationship between basic nuclear processes, epigenetic changes and the numerous proteins that orchestrate these effects. One such protein, ATRX, contains a highly conserved plant homeodomain (PHD)-like domain, present in many chromatin-associated proteins, and a carboxy-terminal domain which identifies it as a member of the SNF2 family of helicase/ATPases. Mutations in ATRX give rise to characteristic developmental abnormalities including severe mental retardation, facial dysmorphism, urogenital abnormalities and alpha-thalassaemia. This circumstantial evidence suggests that ATRX may act as a transcriptional regulator through an effect on chromatin. We have recently shown that ATRX is localized to pericentromeric heterochromatin during interphase and mitosis, suggesting that ATRX might exert other chromatin-mediated effects in the nucleus. Moreover, at metaphase, some ATRX is localized at or close to the ribosomal DNA (rDNA) arrays on the short arms of human acrocentric chromosomes. Here we show that mutations in ATRX give rise to changes in the pattern of methylation of several highly repeated sequences including the rDNA arrays, a Y-specific satellite and subtelomeric repeats. Our findings provide a potential link between the processes of chromatin remodelling, DNA methylation and gene expression in mammalian development.

Windows Terminal Servers Orchestration

NASA Astrophysics Data System (ADS)

Bukowiec, Sebastian; Gaspar, Ricardo; Smith, Tim

2017-10-01

Windows Terminal Servers provide application gateways for various parts of the CERN accelerator complex, used by hundreds of CERN users every day. The combination of new tools such as Puppet, HAProxy and Microsoft System Center suite enable automation of provisioning workflows to provide a terminal server infrastructure that can scale up and down in an automated manner. The orchestration does not only reduce the time and effort necessary to deploy new instances, but also facilitates operations such as patching, analysis and recreation of compromised nodes as well as catering for workload peaks.

Inflammation and cancer

PubMed Central

Coussens, Lisa M.; Werb, Zena

2009-01-01

Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development. PMID:12490959

Drosophila: An Emergent Model for Delineating Interactions between the Circadian Clock and Drugs of Abuse

PubMed Central

De Nobrega, Aliza K.

2017-01-01

Endogenous circadian oscillators orchestrate rhythms at the cellular, physiological, and behavioral levels across species to coordinate activity, for example, sleep/wake cycles, metabolism, and learning and memory, with predictable environmental cycles. The 21st century has seen a dramatic rise in the incidence of circadian and sleep disorders with globalization, technological advances, and the use of personal electronics. The circadian clock modulates alcohol- and drug-induced behaviors with circadian misalignment contributing to increased substance use and abuse. Invertebrate models, such as Drosophila melanogaster, have proven invaluable for the identification of genetic and molecular mechanisms underlying highly conserved processes including the circadian clock, drug tolerance, and reward systems. In this review, we highlight the contributions of Drosophila as a model system for understanding the bidirectional interactions between the circadian system and the drugs of abuse, alcohol and cocaine, and illustrate the highly conserved nature of these interactions between Drosophila and mammalian systems. Research in Drosophila provides mechanistic insights into the corresponding behaviors in higher organisms and can be used as a guide for targeted inquiries in mammals. PMID:29391952

Review paper: DNA delivery strategies to promote periodontal regeneration.

PubMed

Elangovan, Satheesh; Karimbux, Nadeem

2010-07-01

Periodontal diseases are caused by bacteria with an inflammatory component that result in the loss of bone and soft tissue around the neck of the teeth. Recent therapies allow clinicians to regenerate some of the lost structures of the periodontium. Regeneration of these lost supporting structures is a highly orchestrated process, involving various cellular and molecular players, leading to the complete restoration of the periodontium (the tooth-supporting apparatus). The introduction of growth factors has positively influenced the clinical outcome of the existing regenerative procedures but the supra-physiological doses and the high cost associated with these growth factors can be drawbacks. Gene therapy may offer some interesting advantages to current therapies. In the field of periodontology, several studies have been conducted to explore the efficacy of delivering the DNA of key growth factors using viral vectors in both periodontal and peri-implant bone regeneration. Relatively few studies have explored the application of nonviral gene therapy in periodontal regeneration. This article is aimed at reviewing the studies conducted so far using viral and nonviral gene delivery approaches to achieve periodontal and peri-implant bone regeneration.

Integrin αIIbβ3 outside-in signaling

PubMed Central

2017-01-01

Integrin αIIbβ3 is a highly abundant heterodimeric platelet receptor that can transmit information bidirectionally across the plasma membrane, and plays a critical role in hemostasis and thrombosis. Upon platelet activation, inside-out signaling pathways increase the affinity of αIIbβ3 for fibrinogen and other ligands. Ligand binding and integrin clustering subsequently stimulate outside-in signaling, which initiates and amplifies a range of cellular events driving essential platelet processes such as spreading, thrombus consolidation, and clot retraction. Integrin αIIbβ3 has served as an excellent model for the study of integrin biology, and it has become clear that integrin outside-in signaling is highly complex and involves a vast array of enzymes, signaling adaptors, and cytoskeletal components. In this review, we provide a concise but comprehensive overview of αIIbβ3 outside-in signaling, focusing on the key players involved, and how they cooperate to orchestrate this critical aspect of platelet biology. We also discuss gaps in the current understanding of αIIbβ3 outside-in signaling and highlight avenues for future investigation. PMID:28794070

Metamodeling-based approach for risk assessment and cost estimation: Application to geological carbon sequestration planning

NASA Astrophysics Data System (ADS)

Sun, Alexander Y.; Jeong, Hoonyoung; González-Nicolás, Ana; Templeton, Thomas C.

2018-04-01

Carbon capture and storage (CCS) is being evaluated globally as a geoengineering measure for significantly reducing greenhouse emission. However, long-term liability associated with potential leakage from these geologic repositories is perceived as a main barrier of entry to site operators. Risk quantification and impact assessment help CCS operators to screen candidate sites for suitability of CO2 storage. Leakage risks are highly site dependent, and a quantitative understanding and categorization of these risks can only be made possible through broad participation and deliberation of stakeholders, with the use of site-specific, process-based models as the decision basis. Online decision making, however, requires that scenarios be run in real time. In this work, a Python based, Leakage Assessment and Cost Estimation (PyLACE) web application was developed for quantifying financial risks associated with potential leakage from geologic carbon sequestration sites. PyLACE aims to assist a collaborative, analytic-deliberative decision making processes by automating metamodel creation, knowledge sharing, and online collaboration. In PyLACE, metamodeling, which is a process of developing faster-to-run surrogates of process-level models, is enabled using a special stochastic response surface method and the Gaussian process regression. Both methods allow consideration of model parameter uncertainties and the use of that information to generate confidence intervals on model outputs. Training of the metamodels is delegated to a high performance computing cluster and is orchestrated by a set of asynchronous job scheduling tools for job submission and result retrieval. As a case study, workflow and main features of PyLACE are demonstrated using a multilayer, carbon storage model.

The Ophidia Stack: Toward Large Scale, Big Data Analytics Experiments for Climate Change

NASA Astrophysics Data System (ADS)

Fiore, S.; Williams, D. N.; D'Anca, A.; Nassisi, P.; Aloisio, G.

2015-12-01

The Ophidia project is a research effort on big data analytics facing scientific data analysis challenges in multiple domains (e.g. climate change). It provides a "datacube-oriented" framework responsible for atomically processing and manipulating scientific datasets, by providing a common way to run distributive tasks on large set of data fragments (chunks). Ophidia provides declarative, server-side, and parallel data analysis, jointly with an internal storage model able to efficiently deal with multidimensional data and a hierarchical data organization to manage large data volumes. The project relies on a strong background on high performance database management and On-Line Analytical Processing (OLAP) systems to manage large scientific datasets. The Ophidia analytics platform provides several data operators to manipulate datacubes (about 50), and array-based primitives (more than 100) to perform data analysis on large scientific data arrays. To address interoperability, Ophidia provides multiple server interfaces (e.g. OGC-WPS). From a client standpoint, a Python interface enables the exploitation of the framework into Python-based eco-systems/applications (e.g. IPython) and the straightforward adoption of a strong set of related libraries (e.g. SciPy, NumPy). The talk will highlight a key feature of the Ophidia framework stack: the "Analytics Workflow Management System" (AWfMS). The Ophidia AWfMS coordinates, orchestrates, optimises and monitors the execution of multiple scientific data analytics and visualization tasks, thus supporting "complex analytics experiments". Some real use cases related to the CMIP5 experiment will be discussed. In particular, with regard to the "Climate models intercomparison data analysis" case study proposed in the EU H2020 INDIGO-DataCloud project, workflows related to (i) anomalies, (ii) trend, and (iii) climate change signal analysis will be presented. Such workflows will be distributed across multiple sites - according to the datasets distribution - and will include intercomparison, ensemble, and outlier analysis. The two-level workflow solution envisioned in INDIGO (coarse grain for distributed tasks orchestration, and fine grain, at the level of a single data analytics cluster instance) will be presented and discussed.

pMHC affinity controls duration of CD8+ T cell–DC interactions and imprints timing of effector differentiation versus expansion

PubMed Central

Sharpe, James; Zehn, Dietmar; Kreutzfeldt, Mario

2016-01-01

During adaptive immune responses, CD8+ T cells with low TCR affinities are released early into the circulation before high-affinity clones become dominant at later time points. How functional avidity maturation is orchestrated in lymphoid tissue and how low-affinity cells contribute to host protection remains unclear. In this study, we used intravital imaging of reactive lymph nodes (LNs) to show that T cells rapidly attached to dendritic cells irrespective of TCR affinity, whereas one day later, the duration of these stable interactions ceased progressively with lowering peptide major histocompatibility complex (pMHC) affinity. This correlated inversely BATF (basic leucine zipper transcription factor, ATF-like) and IRF4 (interferon-regulated factor 4) induction and timing of effector differentiation, as low affinity–primed T cells acquired cytotoxic activity earlier than high affinity–primed ones. After activation, low-affinity effector CD8+ T cells accumulated at efferent lymphatic vessels for egress, whereas high affinity–stimulated CD8+ T cells moved to interfollicular regions in a CXCR3-dependent manner for sustained pMHC stimulation and prolonged expansion. The early release of low-affinity effector T cells led to rapid target cell elimination outside reactive LNs. Our data provide a model for affinity-dependent spatiotemporal orchestration of CD8+ T cell activation inside LNs leading to functional avidity maturation and uncover a role for low-affinity effector T cells during early microbial containment. PMID:27799622

Palatogenesis and cutaneous repair: a two headed coin

PubMed Central

Biggs, Leah C.; Goudy, Steven L.; Dunnwald, Martine

2014-01-01

The reparative mechanism that operates following post-natal cutaneous injury is a fundamental survival function that requires a well-orchestrated series of molecular and cellular events. At the end, the body will have closed the hole using processes like cellular proliferation, migration, differentiation and fusion. These processes are similar to those occurring during embryogenesis and tissue morphogenesis. Palatogenesis, the formation of the palate from two independent palatal shelves growing towards each other and fusing, intuitively, shares many similarities with the closure of a cutaneous wound from the two migrating epithelial fronts. In this review, we summarize the current information on cutaneous development, wound healing, palatogenesis and orofacial clefting and propose that orofacial clefting and wound healing are conserved processes that share common pathways and gene regulatory networks. PMID:25370680

Concurrent Timbres in Orchestration: a Perceptual Study of Factors Determining "blend"

NASA Astrophysics Data System (ADS)

Sandell, Gregory John

Orchestration often involves selecting instruments for concurrent presentation, as in melodic doubling or chords. One evaluation of the aural outcome of such choices is along the continuum of "blend": whether the instruments fuse into a single composite timbre, segregate into distinct timbral entities, or fall somewhere in between the two extremes. This study investigates, through perceptual experimentation, the acoustical correlates of blend for 15 natural-sounding orchestral instruments presented in concurrently-sounding pairs (e.g. flute-cello, trumpet -oboe, etc.). Ratings of blend showed primary effects for centroid (the location of the midpoint of the spectral energy distribution) and duration of the onset for the tones. Lower average values of both centroid and onset duration for a pair of tones led to increased blends, as did closeness in value for the two factors. Blend decreased (instruments segregated) with higher average values or increased difference in value for the two factors. The musical interval of presentation slightly affected the relative importance of these two mechanisms, with unison intervals determined more by lower average centroid, and minor thirds determined more by closeness in centroid. The contribution of onset in general was slightly more pronounced in the unison conditions than in the minor third condition. Additional factors contributing to blend were correlation of amplitude and centroid envelopes (blend increased as temporal patterns rose and fell in synchrony) and similarity in the overall amount of fundamental frequency perturbation (decreased blend with increasing jitter from both tones). To confirm the importance of centroid as an independent factor determining blend, pairs of tones including instruments with artificially changed centroids were rated for blend. Judgments for several versions of the same instrument pair showed that blend decreased as the altered instrument increased in centroid, corroborating the earlier experiments. Other factors manipulated were amplitude level and the degree of inharmonicity. A survey of orchestration manuals showed many illustrations of "blending" combinations of instruments that were consistent with the results of these experiments. This study's acoustically-based guidelines for blend augment instance-based methods of traditional orchestration teaching, providing underlying abstractions helpful for evaluating the blend of arbitrary combinations of instruments.

Meteorological phenomena in Western classical orchestral music

NASA Astrophysics Data System (ADS)

Williams, P. D.; Aplin, K. L.

2012-12-01

The creative output of composers, writers, and artists is often influenced by their surroundings. To give a literary example, it has been claimed recently that some of the characters in Oliver Twist and A Christmas Carol were based on real-life people who lived near Charles Dickens in London. Of course, an important part of what we see and hear is not only the people with whom we interact, but also our geophysical surroundings. Of all the geophysical phenomena to influence us, the weather is arguably the most significant, because we are exposed to it directly and daily. The weather was a great source of inspiration for Monet, Constable, and Turner, who are known for their scientifically accurate paintings of the skies. But to what extent does weather inspire composers? The authors of this presentation, who are atmospheric scientists by day but amateur classical musicians by night, have been contemplating this question. We have built a systematic musical database, which has allowed us to catalogue and analyze the frequencies with which weather is depicted in a sample of classical orchestral music. The depictions vary from explicit mimicry using traditional and specialized orchestral instruments, through to subtle suggestions. We have found that composers are generally influenced by their own environment in the type of weather they choose to represent. As befits the national stereotype, British composers seem disproportionately keen to depict the UK's variable weather patterns and stormy coastline. Reference: Aplin KL and Williams PD (2011) Meteorological phenomena in Western classical orchestral music. Weather, 66(11), pp 300-306. doi:10.1002/wea.765

MROrchestrator: A Fine-Grained Resource Orchestration Framework for MapReduce Clusters

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

Sharma, Bikash; Prabhakar, Ramya; Kandemir, Mahmut

2012-01-01

Efficient resource management in data centers and clouds running large distributed data processing frameworks like MapReduce is crucial for enhancing the performance of hosted applications and boosting resource utilization. However, existing resource scheduling schemes in Hadoop MapReduce allocate resources at the granularity of fixed-size, static portions of nodes, called slots. In this work, we show that MapReduce jobs have widely varying demands for multiple resources, making the static and fixed-size slot-level resource allocation a poor choice both from the performance and resource utilization standpoints. Furthermore, lack of co-ordination in the management of mul- tiple resources across nodes prevents dynamic slotmore » reconfigura- tion, and leads to resource contention. Motivated by this, we propose MROrchestrator, a MapReduce resource Orchestrator framework, which can dynamically identify resource bottlenecks, and resolve them through fine-grained, co-ordinated, and on- demand resource allocations. We have implemented MROrches- trator on two 24-node native and virtualized Hadoop clusters. Experimental results with a suite of representative MapReduce benchmarks demonstrate up to 38% reduction in job completion times, and up to 25% increase in resource utilization. We further show how popular resource managers like NGM and Mesos when augmented with MROrchestrator can hike up their performance.« less

MYC2 Orchestrates a Hierarchical Transcriptional Cascade That Regulates Jasmonate-Mediated Plant Immunity in Tomato.

PubMed

Du, Minmin; Zhao, Jiuhai; Tzeng, David T W; Liu, Yuanyuan; Deng, Lei; Yang, Tianxia; Zhai, Qingzhe; Wu, Fangming; Huang, Zhuo; Zhou, Ming; Wang, Qiaomei; Chen, Qian; Zhong, Silin; Li, Chang-Bao; Li, Chuanyou

2017-08-01

The hormone jasmonate (JA), which functions in plant immunity, regulates resistance to pathogen infection and insect attack through triggering genome-wide transcriptional reprogramming in plants. We show that the basic helix-loop-helix transcription factor (TF) MYC2 in tomato ( Solanum lycopersicum ) acts downstream of the JA receptor to orchestrate JA-mediated activation of both the wounding and pathogen responses. Using chromatin immunoprecipitation sequencing (ChIP-seq) coupled with RNA sequencing (RNA-seq) assays, we identified 655 MYC2-targeted JA-responsive genes. These genes are highly enriched in Gene Ontology categories related to TFs and the early response to JA, indicating that MYC2 functions at a high hierarchical level to regulate JA-mediated gene transcription. We also identified a group of MYC2-targeted TFs (MTFs) that may directly regulate the JA-induced transcription of late defense genes. Our findings suggest that MYC2 and its downstream MTFs form a hierarchical transcriptional cascade during JA-mediated plant immunity that initiates and amplifies transcriptional output. As proof of concept, we showed that during plant resistance to the necrotrophic pathogen Botrytis cinerea , MYC2 and the MTF JA2-Like form a transcription module that preferentially regulates wounding-responsive genes, whereas MYC2 and the MTF ETHYLENE RESPONSE FACTOR.C3 form a transcription module that preferentially regulates pathogen-responsive genes. © 2017 American Society of Plant Biologists. All rights reserved.

MYC2 Orchestrates a Hierarchical Transcriptional Cascade That Regulates Jasmonate-Mediated Plant Immunity in Tomato[OPEN

PubMed Central

Liu, Yuanyuan; Deng, Lei; Wu, Fangming; Huang, Zhuo; Zhou, Ming; Chen, Qian; Zhong, Silin

2017-01-01

The hormone jasmonate (JA), which functions in plant immunity, regulates resistance to pathogen infection and insect attack through triggering genome-wide transcriptional reprogramming in plants. We show that the basic helix-loop-helix transcription factor (TF) MYC2 in tomato (Solanum lycopersicum) acts downstream of the JA receptor to orchestrate JA-mediated activation of both the wounding and pathogen responses. Using chromatin immunoprecipitation sequencing (ChIP-seq) coupled with RNA sequencing (RNA-seq) assays, we identified 655 MYC2-targeted JA-responsive genes. These genes are highly enriched in Gene Ontology categories related to TFs and the early response to JA, indicating that MYC2 functions at a high hierarchical level to regulate JA-mediated gene transcription. We also identified a group of MYC2-targeted TFs (MTFs) that may directly regulate the JA-induced transcription of late defense genes. Our findings suggest that MYC2 and its downstream MTFs form a hierarchical transcriptional cascade during JA-mediated plant immunity that initiates and amplifies transcriptional output. As proof of concept, we showed that during plant resistance to the necrotrophic pathogen Botrytis cinerea, MYC2 and the MTF JA2-Like form a transcription module that preferentially regulates wounding-responsive genes, whereas MYC2 and the MTF ETHYLENE RESPONSE FACTOR.C3 form a transcription module that preferentially regulates pathogen-responsive genes. PMID:28733419

High rates of intestinal bicarbonate secretion in seawater tilapia (Oreochromis mossambicus).

PubMed

Ruiz-Jarabo, I; Gregório, S F; Gaetano, P; Trischitta, F; Fuentes, J

2017-05-01

Osmoregulation in fish is a complex process that requires the orchestrated cooperation of many tissues. In fish facing hyperosmotic environments, the intestinal absorption of some monovalent ions and the secretion of bicarbonate are key processes to favor water absorption. In the present study, we showed that bicarbonate levels in the intestinal fluid are several fold higher in seawater than in freshwater acclimated tilapia (Oreochromis mossambicus). In addition, we analyzed gene expression of the main molecular mechanisms involved in HCO 3 - movements i.e. slc26a6, slc26a3, slc4a4 and v-type H-ATPase sub C in the intestine of tilapia acclimated to both seawater and freshwater. Our results show an anterior/posterior functional regionalization of the intestine in tilapia in terms of expression patterns, which is affected by environmental salinity mostly in the anterior and mid intestine. Analysis of bicarbonate secretion using pH-Stat in tissues mounted in Ussing chambers reveals high rates of bicarbonate secretion in tilapia acclimated to seawater from anterior intestine to rectum ranging between ~900 and ~1700nmolHCO 3 - cm -2 h -1 . However, a relationship between the expression of slc26a6, slc26a3, slc4a4 and the rate of bicarbonate secretion seems to be compromised in the rectum. In this region, the low expression of the bicarbonate transporters could not explain the high bicarbonate secretion rates here described. However, we postulate that the elevated v-type H-ATPase mRNA expression in the rectum could be involved in this process. Copyright © 2017 Elsevier Inc. All rights reserved.

Automation Hooks Architecture for Flexible Test Orchestration - Concept Development and Validation

NASA Technical Reports Server (NTRS)

Lansdowne, C. A.; Maclean, John R.; Winton, Chris; McCartney, Pat

2011-01-01

The Automation Hooks Architecture Trade Study for Flexible Test Orchestration sought a standardized data-driven alternative to conventional automated test programming interfaces. The study recommended composing the interface using multicast DNS (mDNS/SD) service discovery, Representational State Transfer (Restful) Web Services, and Automatic Test Markup Language (ATML). We describe additional efforts to rapidly mature the Automation Hooks Architecture candidate interface definition by validating it in a broad spectrum of applications. These activities have allowed us to further refine our concepts and provide observations directed toward objectives of economy, scalability, versatility, performance, severability, maintainability, scriptability and others.

FERMT2 links cortical actin structures, plasma membrane tension and focal adhesion function to stabilize podocyte morphology.

PubMed

Yasuda-Yamahara, M; Rogg, M; Frimmel, J; Trachte, P; Helmstaedter, M; Schroder, P; Schiffer, M; Schell, C; Huber, T B

2018-01-11

Simplification and retraction of podocyte protrusions, generally termed as foot process effacement, is a uniform pathological pattern observed in the majority of glomerular disease, including focal segmental glomerulosclerosis. However, it is still incompletely understood how the interaction of cortical actin structures, actomyosin contractility and focal adhesions, is being orchestrated to control foot process morphology in health and disease. By uncovering the functional role of fermitin family member 2 (FERMT2 or kindlin-2) in podocytes, we provide now evidence, how cell-extracellular matrix (ECM) interactions modulate membrane tension and actomyosin contractility. A genetic modeling approach was applied by deleting FERMT2 in a set of in vivo systems as well as in CRISPR/Cas9 modified human podocytes. Loss of FERMT2 results in altered cortical actin composition, cell cortex destabilization associated with plasma membrane blebbing and a remodeling of focal adhesions. We further show that FERMT2 knockout podocytes have high levels of RhoA activation and concomitantly increased actomyosin contractility. Inhibition of actomyosin tension reverses the membrane blebbing phenotype. Thus, our findings establish a direct link between cell-matrix adhesions, cortical actin structures and plasma membrane tension allowing to better explain cell morphological changes in foot process effacement. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Decoding transcriptional enhancers: Evolving from annotation to functional interpretation

PubMed Central

Engel, Krysta L.; Mackiewicz, Mark; Hardigan, Andrew A.; Myers, Richard M.; Savic, Daniel

2016-01-01

Deciphering the intricate molecular processes that orchestrate the spatial and temporal regulation of genes has become an increasingly major focus of biological research. The differential expression of genes by diverse cell types with a common genome is a hallmark of complex cellular functions, as well as the basis for multicellular life. Importantly, a more coherent understanding of gene regulation is critical for defining developmental processes, evolutionary principles and disease etiologies. Here we present our current understanding of gene regulation by focusing on the role of enhancer elements in these complex processes. Although functional genomic methods have provided considerable advances to our understanding of gene regulation, these assays, which are usually performed on a genome-wide scale, typically provide correlative observations that lack functional interpretation. Recent innovations in genome editing technologies have placed gene regulatory studies at an exciting crossroads, as systematic, functional evaluation of enhancers and other transcriptional regulatory elements can now be performed in a coordinated, high-throughput manner across the entire genome. This review provides insights on transcriptional enhancer function, their role in development and disease, and catalogues experimental tools commonly used to study these elements. Additionally, we discuss the crucial role of novel techniques in deciphering the complex gene regulatory landscape and how these studies will shape future research. PMID:27224938

Decoding transcriptional enhancers: Evolving from annotation to functional interpretation.

PubMed

Engel, Krysta L; Mackiewicz, Mark; Hardigan, Andrew A; Myers, Richard M; Savic, Daniel

2016-09-01

Deciphering the intricate molecular processes that orchestrate the spatial and temporal regulation of genes has become an increasingly major focus of biological research. The differential expression of genes by diverse cell types with a common genome is a hallmark of complex cellular functions, as well as the basis for multicellular life. Importantly, a more coherent understanding of gene regulation is critical for defining developmental processes, evolutionary principles and disease etiologies. Here we present our current understanding of gene regulation by focusing on the role of enhancer elements in these complex processes. Although functional genomic methods have provided considerable advances to our understanding of gene regulation, these assays, which are usually performed on a genome-wide scale, typically provide correlative observations that lack functional interpretation. Recent innovations in genome editing technologies have placed gene regulatory studies at an exciting crossroads, as systematic, functional evaluation of enhancers and other transcriptional regulatory elements can now be performed in a coordinated, high-throughput manner across the entire genome. This review provides insights on transcriptional enhancer function, their role in development and disease, and catalogues experimental tools commonly used to study these elements. Additionally, we discuss the crucial role of novel techniques in deciphering the complex gene regulatory landscape and how these studies will shape future research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Non-thermal Plasma Activates Human Keratinocytes by Stimulation of Antioxidant and Phase II Pathways

PubMed Central

Schmidt, Anke; Dietrich, Stephan; Steuer, Anna; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Masur, Kai; Wende, Kristian

2015-01-01

Non-thermal atmospheric pressure plasma provides a novel therapeutic opportunity to control redox-based processes, e.g. wound healing, cancer, and inflammatory diseases. By spatial and time-resolved delivery of reactive oxygen and nitrogen species, it allows stimulation or inhibition of cellular processes in biological systems. Our data show that both gene and protein expression is highly affected by non-thermal plasma. Nuclear factor erythroid-related factor 2 (NRF2) and phase II enzyme pathway components were found to act as key controllers orchestrating the cellular response in keratinocytes. Additionally, glutathione metabolism, which is a marker for NRF2-related signaling events, was affected. Among the most robustly increased genes and proteins, heme oxygenase 1, NADPH-quinone oxidoreductase 1, and growth factors were found. The roles of NRF2 targets, investigated by siRNA silencing, revealed that NRF2 acts as an important switch for sensing oxidative stress events. Moreover, the influence of non-thermal plasma on the NRF2 pathway prepares cells against exogenic noxae and increases their resilience against oxidative species. Via paracrine mechanisms, distant cells benefit from cell-cell communication. The finding that non-thermal plasma triggers hormesis-like processes in keratinocytes facilitates the understanding of plasma-tissue interaction and its clinical application. PMID:25589789

A primer on caspase mechanisms.

PubMed

Ramirez, Monica L Gonzalez; Salvesen, Guy S

2018-01-12

Caspases belong to a diverse clan of proteolytic enzymes known as clan CD with highly disparate functions in cell signaling. The caspase members of this clan are only found in animals, and most of them orchestrate the demise of cells by the highly distinct regulated cell death phenotypes known as apoptosis and pyroptosis. This review looks at the mechanistic distinctions between the activity and activation mechanisms of mammalian caspases compared to other members of clan CD. We also compare and contrast the role of different caspase family members that program anti-inflammatory and pro-inflammatory cell death pathways. Copyright © 2018. Published by Elsevier Ltd.

Elicitor-induced transcription factors for metabolic reprogramming of secondary metabolism in Medicago truncatula

PubMed Central

Naoumkina, Marina A; He, XianZhi; Dixon, Richard A

2008-01-01

Background Exposure of Medicago truncatula cell suspension cultures to pathogen or wound signals leads to accumulation of various classes of flavonoid and/or triterpene defense molecules, orchestrated via a complex signalling network in which transcription factors (TFs) are essential components. Results In this study, we analyzed TFs responding to yeast elicitor (YE) or methyl jasmonate (MJ). From 502 differentially expressed TFs, WRKY and AP2/EREBP gene families were over-represented among YE-induced genes whereas Basic Helix-Loop-Helix (bHLH) family members were more over-represented among the MJ-induced genes. Jasmonate ZIM-domain (JAZ) transcriptional regulators were highly induced by MJ treatment. To investigate potential involvement of WRKY TFs in signalling, we expressed four Medicago WRKY genes in tobacco. Levels of soluble and wall bound phenolic compounds and lignin were increased in all cases. WRKY W109669 also induced tobacco endo-1,3-β-glucanase (NtPR2) and enhanced the systemic defense response to tobacco mosaic virus in transgenic tobacco plants. Conclusion These results confirm that Medicago WRKY TFs have broad roles in orchestrating metabolic responses to biotic stress, and that they also represent potentially valuable reagents for engineering metabolic changes that impact pathogen resistance. PMID:19102779

Towards Dynamic Service Level Agreement Negotiation:An Approach Based on WS-Agreement

NASA Astrophysics Data System (ADS)

Pichot, Antoine; Wäldrich, Oliver; Ziegler, Wolfgang; Wieder, Philipp

In Grid, e-Science and e-Business environments, Service Level Agreements are often used to establish frameworks for the delivery of services between service providers and the organisations hosting the researchers. While this high level SLAs define the overall quality of the services, it is desirable for the end-user to have dedicated service quality also for individual services like the orchestration of resources necessary for composed services. Grid level scheduling services typically are responsible for the orchestration and co-ordination of resources in the Grid. Co-allocation e.g. requires the Grid level scheduler to co-ordinate resource management systems located in different domains. As the site autonomy has to be respected negotiation is the only way to achieve the intended co-ordination. SLAs emerged as a new way to negotiate and manage usage of resources in the Grid and are already adopted by a number of management systems. Therefore, it is natural to look for ways to adopt SLAs for Grid level scheduling. In order to do this, efficient and flexible protocols are needed, which support dynamic negotiation and creation of SLAs. In this paper we propose and discuss extensions to the WS-Agreement protocol addressing these issues.

Reliable and Fault-Tolerant Software-Defined Network Operations Scheme for Remote 3D Printing

NASA Astrophysics Data System (ADS)

Kim, Dongkyun; Gil, Joon-Min

2015-03-01

The recent wide expansion of applicable three-dimensional (3D) printing and software-defined networking (SDN) technologies has led to a great deal of attention being focused on efficient remote control of manufacturing processes. SDN is a renowned paradigm for network softwarization, which has helped facilitate remote manufacturing in association with high network performance, since SDN is designed to control network paths and traffic flows, guaranteeing improved quality of services by obtaining network requests from end-applications on demand through the separated SDN controller or control plane. However, current SDN approaches are generally focused on the controls and automation of the networks, which indicates that there is a lack of management plane development designed for a reliable and fault-tolerant SDN environment. Therefore, in addition to the inherent advantage of SDN, this paper proposes a new software-defined network operations center (SD-NOC) architecture to strengthen the reliability and fault-tolerance of SDN in terms of network operations and management in particular. The cooperation and orchestration between SDN and SD-NOC are also introduced for the SDN failover processes based on four principal SDN breakdown scenarios derived from the failures of the controller, SDN nodes, and connected links. The abovementioned SDN troubles significantly reduce the network reachability to remote devices (e.g., 3D printers, super high-definition cameras, etc.) and the reliability of relevant control processes. Our performance consideration and analysis results show that the proposed scheme can shrink operations and management overheads of SDN, which leads to the enhancement of responsiveness and reliability of SDN for remote 3D printing and control processes.

Transposable elements as genetic regulatory substrates in early development.

PubMed

Gifford, Wesley D; Pfaff, Samuel L; Macfarlan, Todd S

2013-05-01

The abundance and ancient origins of transposable elements (TEs) in eukaryotic genomes has spawned research into the potential symbiotic relationship between these elements and their hosts. In this review, we introduce the diversity of TEs, discuss how distinct classes are uniquely regulated in development, and describe how they appear to have been coopted for the purposes of gene regulation and the orchestration of a number of processes during early embryonic development. Although young, active TEs play an important role in somatic tissues and evolution, we focus mostly on the contributions of the older, fixed elements in mammalian genomes. We also discuss major challenges inherent in the study of TEs and contemplate future experimental approaches to further investigate how they coordinate developmental processes. Published by Elsevier Ltd.

Transposable elements as genetic regulatory substrates in early development

PubMed Central

Gifford, Wesley D.; Pfaff, Samuel L.; Macfarlan, Todd S.

2014-01-01

The abundance and ancient origins of transposable elements (TEs) in eukaryotic genomes has spawned research into the potential symbiotic relationship between these elements and their hosts. In this review, we introduce the diversity of TEs, discuss how distinct classes are uniquely regulated in development, and describe how they appear to have been coopted for the purposes of gene regulation and the orchestration of a number of processes during early embryonic development. Although young, active TEs play an important role in somatic tissues and evolution, we focus mostly on the contributions of the older, fixed elements in mammalian genomes. We also discuss major challenges inherent in the study of TEs and contemplate future experimental approaches to further investigate how they coordinate developmental processes. PMID:23411159

Cell-accurate optical mapping across the entire developing heart.

PubMed

Weber, Michael; Scherf, Nico; Meyer, Alexander M; Panáková, Daniela; Kohl, Peter; Huisken, Jan

2017-12-29

Organogenesis depends on orchestrated interactions between individual cells and morphogenetically relevant cues at the tissue level. This is true for the heart, whose function critically relies on well-ordered communication between neighboring cells, which is established and fine-tuned during embryonic development. For an integrated understanding of the development of structure and function, we need to move from isolated snap-shot observations of either microscopic or macroscopic parameters to simultaneous and, ideally continuous, cell-to-organ scale imaging. We introduce cell-accurate three-dimensional Ca 2+ -mapping of all cells in the entire electro-mechanically uncoupled heart during the looping stage of live embryonic zebrafish, using high-speed light sheet microscopy and tailored image processing and analysis. We show how myocardial region-specific heterogeneity in cell function emerges during early development and how structural patterning goes hand-in-hand with functional maturation of the entire heart. Our method opens the way to systematic, scale-bridging, in vivo studies of vertebrate organogenesis by cell-accurate structure-function mapping across entire organs.

A dynamic cellular vertex model of growing epithelial tissues

NASA Astrophysics Data System (ADS)

Lin, Shao-Zhen; Li, Bo; Feng, Xi-Qiao

2017-04-01

Intercellular interactions play a significant role in a wide range of biological functions and processes at both the cellular and tissue scales, for example, embryogenesis, organogenesis, and cancer invasion. In this paper, a dynamic cellular vertex model is presented to study the morphomechanics of a growing epithelial monolayer. The regulating role of stresses in soft tissue growth is revealed. It is found that the cells originating from the same parent cell in the monolayer can orchestrate into clustering patterns as the tissue grows. Collective cell migration exhibits a feature of spatial correlation across multiple cells. Dynamic intercellular interactions can engender a variety of distinct tissue behaviors in a social context. Uniform cell proliferation may render high and heterogeneous residual compressive stresses, while stress-regulated proliferation can effectively release the stresses, reducing the stress heterogeneity in the tissue. The results highlight the critical role of mechanical factors in the growth and morphogenesis of epithelial tissues and help understand the development and invasion of epithelial tumors.

The increasing diversity of functions attributed to the SAFB family of RNA-/DNA-binding proteins.

PubMed

Norman, Michael; Rivers, Caroline; Lee, Youn-Bok; Idris, Jalilah; Uney, James

2016-12-01

RNA-binding proteins play a central role in cellular metabolism by orchestrating the complex interactions of coding, structural and regulatory RNA species. The SAFB (scaffold attachment factor B) proteins (SAFB1, SAFB2 and SAFB-like transcriptional modulator, SLTM), which are highly conserved evolutionarily, were first identified on the basis of their ability to bind scaffold attachment region DNA elements, but attention has subsequently shifted to their RNA-binding and protein-protein interactions. Initial studies identified the involvement of these proteins in the cellular stress response and other aspects of gene regulation. More recently, the multifunctional capabilities of SAFB proteins have shown that they play crucial roles in DNA repair, processing of mRNA and regulatory RNA, as well as in interaction with chromatin-modifying complexes. With the advent of new techniques for identifying RNA-binding sites, enumeration of individual RNA targets has now begun. This review aims to summarise what is currently known about the functions of SAFB proteins. © 2016 The Author(s).

A lateral signalling pathway coordinates shape volatility during cell migration

PubMed Central

Zhang, Liang; Luga, Valbona; Armitage, Sarah K.; Musiol, Martin; Won, Amy; Yip, Christopher M.; Plotnikov, Sergey V.; Wrana, Jeffrey L.

2016-01-01

Cell migration is fundamental for both physiological and pathological processes. Migrating cells usually display high dynamics in morphology, which is orchestrated by an integrative array of signalling pathways. Here we identify a novel pathway, we term lateral signalling, comprised of the planar cell polarity (PCP) protein Pk1 and the RhoGAPs, Arhgap21/23. We show that the Pk1–Arhgap21/23 complex inhibits RhoA, is localized on the non-protrusive lateral membrane cortex and its disruption leads to the disorganization of the actomyosin network and altered focal adhesion dynamics. Pk1-mediated lateral signalling confines protrusive activity and is regulated by Smurf2, an E3 ubiquitin ligase in the PCP pathway. Furthermore, we demonstrate that dynamic interplay between lateral and protrusive signalling generates cyclical fluctuations in cell shape that we quantify here as shape volatility, which strongly correlates with migration speed. These studies uncover a previously unrecognized lateral signalling pathway that coordinates shape volatility during productive cell migration. PMID:27226243

"Silent" NMDA Synapses Enhance Motion Sensitivity in a Mature Retinal Circuit.

PubMed

Sethuramanujam, Santhosh; Yao, Xiaoyang; deRosenroll, Geoff; Briggman, Kevin L; Field, Greg D; Awatramani, Gautam B

2017-12-06

Retinal direction-selective ganglion cells (DSGCs) have the remarkable ability to encode motion over a wide range of contrasts, relying on well-coordinated excitation and inhibition (E/I). E/I is orchestrated by a diverse set of glutamatergic bipolar cells that drive DSGCs directly, as well as indirectly through feedforward GABAergic/cholinergic signals mediated by starburst amacrine cells. Determining how direction-selective responses are generated across varied stimulus conditions requires understanding how glutamate, acetylcholine, and GABA signals are precisely coordinated. Here, we use a combination of paired patch-clamp recordings, serial EM, and large-scale multi-electrode array recordings to show that a single high-sensitivity source of glutamate is processed differentially by starbursts via AMPA receptors and DSGCs via NMDA receptors. We further demonstrate how this novel synaptic arrangement enables DSGCs to encode direction robustly near threshold contrasts. Together, these results reveal a space-efficient synaptic circuit model for direction computations, in which "silent" NMDA receptors play critical roles. Copyright © 2017 Elsevier Inc. All rights reserved.

Cell-accurate optical mapping across the entire developing heart

PubMed Central

Meyer, Alexander M; Panáková, Daniela; Kohl, Peter

2017-01-01

Organogenesis depends on orchestrated interactions between individual cells and morphogenetically relevant cues at the tissue level. This is true for the heart, whose function critically relies on well-ordered communication between neighboring cells, which is established and fine-tuned during embryonic development. For an integrated understanding of the development of structure and function, we need to move from isolated snap-shot observations of either microscopic or macroscopic parameters to simultaneous and, ideally continuous, cell-to-organ scale imaging. We introduce cell-accurate three-dimensional Ca2+-mapping of all cells in the entire electro-mechanically uncoupled heart during the looping stage of live embryonic zebrafish, using high-speed light sheet microscopy and tailored image processing and analysis. We show how myocardial region-specific heterogeneity in cell function emerges during early development and how structural patterning goes hand-in-hand with functional maturation of the entire heart. Our method opens the way to systematic, scale-bridging, in vivo studies of vertebrate organogenesis by cell-accurate structure-function mapping across entire organs. PMID:29286002

Theory of meiotic spindle assembly

NASA Astrophysics Data System (ADS)

Furthauer, Sebastian; Foster, Peter; Needleman, Daniel; Shelley, Michael

2016-11-01

The meiotic spindle is a biological structure that self assembles from the intracellular medium to separate chromosomes during meiosis. It consists of filamentous microtubule (MT) proteins that interact through the fluid in which they are suspended and via the associated molecules that orchestrate their behavior. We aim to understand how the interplay between fluid medium, MTs, and regulatory proteins allows this material to self-organize into the spindle's highly stereotyped shape. To this end we develop a continuum model that treats the spindle as an active liquid crystal with MT turnover. In this active material, molecular motors, such as dyneins which collect MT minus ends and kinesins which slide MTs past each other, generate active fluid and material stresses. Moreover nucleator proteins that are advected with and transported along MTs control the nucleation and depolymerization of MTs. This theory captures the growth process of meiotic spindles, their shapes, and the essential features of many perturbation experiments. It thus provides a framework to think about the physics of this complex biological suspension.

Microprocessor, Setx, Xrn2, and Rrp6 co-operate to induce premature termination of transcription by RNAPII.

PubMed

Wagschal, Alexandre; Rousset, Emilie; Basavarajaiah, Poornima; Contreras, Xavier; Harwig, Alex; Laurent-Chabalier, Sabine; Nakamura, Mirai; Chen, Xin; Zhang, Ke; Meziane, Oussama; Boyer, Frédéric; Parrinello, Hugues; Berkhout, Ben; Terzian, Christophe; Benkirane, Monsef; Kiernan, Rosemary

2012-09-14

Transcription elongation is increasingly recognized as an important mechanism of gene regulation. Here, we show that microprocessor controls gene expression in an RNAi-independent manner. Microprocessor orchestrates the recruitment of termination factors Setx and Xrn2, and the 3'-5' exoribonuclease, Rrp6, to initiate RNAPII pausing and premature termination at the HIV-1 promoter through cleavage of the stem-loop RNA, TAR. Rrp6 further processes the cleavage product, which generates a small RNA that is required to mediate potent transcriptional repression and chromatin remodeling at the HIV-1 promoter. Using chromatin immunoprecipitation coupled to high-throughput sequencing (ChIP-seq), we identified cellular gene targets whose transcription is modulated by microprocessor. Our study reveals RNAPII pausing and premature termination mediated by the co-operative activity of ribonucleases, Drosha/Dgcr8, Xrn2, and Rrp6, as a regulatory mechanism of RNAPII-dependent transcription elongation. Copyright © 2012 Elsevier Inc. All rights reserved.

FOXO1 expression in keratinocytes promotes connective tissue healing

PubMed Central

Zhang, Chenying; Lim, Jason; Liu, Jian; Ponugoti, Bhaskar; Alsadun, Sarah; Tian, Chen; Vafa, Rameen; Graves, Dana T.

2017-01-01

Wound healing is complex and highly orchestrated. It is well appreciated that leukocytes, particularly macrophages, are essential for inducing the formation of new connective tissue, which requires the generation of signals that stimulate mesenchymal stem cells (MSC), myofibroblasts and fibroblasts. A key role for keratinocytes in this complex process has yet to be established. To this end, we investigated possible involvement of keratinocytes in connective tissue healing. By lineage-specific deletion of the forkhead box-O 1 (FOXO1) transcription factor, we demonstrate for the first time that keratinocytes regulate proliferation of fibroblasts and MSCs, formation of myofibroblasts and production of collagen matrix in wound healing. This stimulation is mediated by a FOXO1 induced TGFβ1/CTGF axis. The results provide direct evidence that epithelial cells play a key role in stimulating connective tissue healing through a FOXO1-dependent mechanism. Thus, FOXO1 and keratinocytes may be an important therapeutic target where healing is deficient or compromised by a fibrotic outcome. PMID:28220813

orco Mutagenesis Causes Loss of Antennal Lobe Glomeruli and Impaired Social Behavior in Ants.

PubMed

Trible, Waring; Olivos-Cisneros, Leonora; McKenzie, Sean K; Saragosti, Jonathan; Chang, Ni-Chen; Matthews, Benjamin J; Oxley, Peter R; Kronauer, Daniel J C

2017-08-10

Life inside ant colonies is orchestrated with diverse pheromones, but it is not clear how ants perceive these social signals. It has been proposed that pheromone perception in ants evolved via expansions in the numbers of odorant receptors (ORs) and antennal lobe glomeruli. Here, we generate the first mutant lines in the clonal raider ant, Ooceraea biroi, by disrupting orco, a gene required for the function of all ORs. We find that orco mutants exhibit severe deficiencies in social behavior and fitness, suggesting they are unable to perceive pheromones. Surprisingly, unlike in Drosophila melanogaster, orco mutant ants also lack most of the ∼500 antennal lobe glomeruli found in wild-type ants. These results illustrate that ORs are essential for ant social organization and raise the possibility that, similar to mammals, receptor function is required for the development and/or maintenance of the highly complex olfactory processing areas in the ant brain. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

Status epilepticus does not induce acute brain inflammatory response in the Amazon rodent Proechimys, an animal model resistant to epileptogenesis.

PubMed

Scorza, Carla A; Marques, Marcia J G; Gomes da Silva, Sérgio; Naffah-Mazzacoratti, Maria da Graça; Scorza, Fulvio A; Cavalheiro, Esper A

2018-03-06

Mesial temporal lobe epilepsy is a serious brain disorder in adults that is often preceded by an initial brain insult, such as status epilepticus (SE), that after a latent period leads to recurrent seizures. Post-SE models are widely used for studies on epileptogenic processes. Previous findings of our laboratory suggested that the Neotropical rodents Proechimys exhibit endogenous antiepileptogenic mechanisms in post-SE models. Strong body of research supports that SE triggers a rapid and dramatic upregulation of inflammatory mediators and vascular endothelial growth factor (VEGF). In this work we found that, in the epilepsy-resistant Proechimys, hippocampal and cortical levels of inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-α) and VEGF remained unchanged 24h after SE, strongly contrasting to the high levels of post-SE changes observed in Wistar rats. Furthermore, substantial differences in the brain baseline levels of these proteins were encountered between animal species studied. Since inflammatory cytokines and VEGF have been recognized as major orchestrators of the epileptogenic process, our results suggest their role in the antiepileptogenic mechanisms previously described in Proechimys. Copyright © 2017 Elsevier B.V. All rights reserved.

Human Prostate Cancer Hallmarks Map

PubMed Central

Datta, Dipamoy; Aftabuddin, Md.; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

2016-01-01

Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process. PMID:27476486

DNA Methylation and Demethylation in Plant Immunity.

PubMed

Deleris, A; Halter, T; Navarro, L

2016-08-04

Detection of plant and animal pathogens triggers a massive transcriptional reprogramming, which is directed by chromatin-based processes, and ultimately results in antimicrobial immunity. Although the implication of histone modifications in orchestrating biotic stress-induced transcriptional reprogramming has been well characterized, very little was known, until recently, about the role of DNA methylation and demethylation in this process. In this review, we summarize recent findings on the dynamics and biological relevance of DNA methylation and demethylation in plant immunity against nonviral pathogens. In particular, we report the implications of these epigenetic regulatory processes in the transcriptional and co-transcriptional control of immune-responsive genes and discuss their relevance in fine-tuning antimicrobial immune responses. Finally, we discuss the possible yet elusive role of DNA methylation and demethylation in systemic immune responses, transgenerational immune priming, and de novo epiallelism, which could be adaptive.

Proteolipidic Composition of Exosomes Changes during Reticulocyte Maturation*

PubMed Central

Carayon, Kévin; Chaoui, Karima; Ronzier, Elsa; Lazar, Ikrame; Bertrand-Michel, Justine; Roques, Véronique; Balor, Stéphanie; Terce, François; Lopez, André; Salomé, Laurence; Joly, Etienne

2011-01-01

During the orchestrated process leading to mature erythrocytes, reticulocytes must synthesize large amounts of hemoglobin, while eliminating numerous cellular components. Exosomes are small secreted vesicles that play an important role in this process of specific elimination. To understand the mechanisms of proteolipidic sorting leading to their biogenesis, we have explored changes in the composition of exosomes released by reticulocytes during their differentiation, in parallel to their physical properties. By combining proteomic and lipidomic approaches, we found dramatic alterations in the composition of the exosomes retrieved over the course of a 7-day in vitro differentiation protocol. Our data support a previously proposed model, whereby in reticulocytes the biogenesis of exosomes involves several distinct mechanisms for the preferential recruitment of particular proteins and lipids and suggest that the respective prominence of those pathways changes over the course of the differentiation process. PMID:21828046

Autophagy in immunity and inflammation

PubMed Central

Levine, Beth; Mizushima, Noboru; Virgin, Herbert W.

2011-01-01

Autophagy is an essential, homeostatic process by which cells break down their own components. Perhaps the most primordial function of this lysosomal degradation pathway is adaptation to nutrient deprivation. However, in complex multicellular organisms, the core molecular machinery of autophagy — the ‘autophagy proteins’ — orchestrates diverse aspects of cellular and organismal responses to other dangerous stimuli such as infection. Recent developments reveal a crucial role for the autophagy pathway and proteins in immunity and inflammation. They balance the beneficial and detrimental effects of immunity and inflammation, and thereby may protect against infectious, autoimmune and inflammatory diseases. PMID:21248839

Complexity of Danger: The Diverse Nature of Damage-associated Molecular Patterns*

PubMed Central

Schaefer, Liliana

2014-01-01

In reply to internal or external danger stimuli, the body orchestrates an inflammatory response. The endogenous triggers of this process are the damage-associated molecular patterns (DAMPs). DAMPs represent a heterogeneous group of molecules that draw their origin either from inside the various compartments of the cell or from the extracellular space. Following interaction with pattern recognition receptors in cross-talk with various non-immune receptors, DAMPs determine the downstream signaling outcome of septic and aseptic inflammatory responses. In this review, the diverse nature, structural characteristics, and signaling pathways elicited by DAMPs will be critically evaluated. PMID:25391648

Biosynthesis of the Urease Metallocenter*

PubMed Central

Farrugia, Mark A.; Macomber, Lee; Hausinger, Robert P.

2013-01-01

Metalloenzymes often require elaborate metallocenter assembly systems to create functional active sites. The medically important dinuclear nickel enzyme urease provides an excellent model for studying metallocenter assembly. Nickel is inserted into the urease active site in a GTP-dependent process with the assistance of UreD/UreH, UreE, UreF, and UreG. These accessory proteins orchestrate apoprotein activation by delivering the appropriate metal, facilitating protein conformational changes, and possibly providing a requisite post-translational modification. The activation mechanism and roles of each accessory protein in urease maturation are the subject of ongoing studies, with the latest findings presented in this minireview. PMID:23539618

The role of MIF in type 1 and type 2 diabetes mellitus.

PubMed

Sánchez-Zamora, Yuriko I; Rodriguez-Sosa, Miriam

2014-01-01

Autoimmunity and chronic low-grade inflammation are hallmarks of diabetes mellitus type one (T1DM) and type two (T2DM), respectively. Both processes are orchestrated by inflammatory cytokines, including the macrophage migration inhibitory factor (MIF). To date, MIF has been implicated in both types of diabetes; therefore, understanding the role of MIF could affect our understanding of the autoimmune or inflammatory responses that influence diabetic pathology. This review highlights our current knowledge about the involvement of MIF in both types of diabetes in the clinical environment and in experimental disease models.

Instrument control software requirement specification for Extremely Large Telescopes

NASA Astrophysics Data System (ADS)

Young, Peter J.; Kiekebusch, Mario J.; Chiozzi, Gianluca

2010-07-01

Engineers in several observatories are now designing the next generation of optical telescopes, the Extremely Large Telescopes (ELT). These are very complex machines that will host sophisticated astronomical instruments to be used for a wide range of scientific studies. In order to carry out scientific observations, a software infrastructure is required to orchestrate the control of the multiple subsystems and functions. This paper will focus on describing the considerations, strategies and main issues related to the definition and analysis of the software requirements for the ELT's Instrument Control System using modern development processes and modelling tools like SysML.

Transcriptional Dynamics Driving MAMP-Triggered Immunity and Pathogen Effector-Mediated Immunosuppression in Arabidopsis Leaves Following Infection with Pseudomonas syringae pv tomato DC3000[OPEN

PubMed Central

Lewis, Laura A.; Polanski, Krzysztof; de Torres-Zabala, Marta; Bowden, Laura; Jenkins, Dafyd J.; Hill, Claire; Baxter, Laura; Truman, William; Prusinska, Justyna; Hickman, Richard; Wild, David L.; Ott, Sascha; Buchanan-Wollaston, Vicky; Beynon, Jim

2015-01-01

Transcriptional reprogramming is integral to effective plant defense. Pathogen effectors act transcriptionally and posttranscriptionally to suppress defense responses. A major challenge to understanding disease and defense responses is discriminating between transcriptional reprogramming associated with microbial-associated molecular pattern (MAMP)-triggered immunity (MTI) and that orchestrated by effectors. A high-resolution time course of genome-wide expression changes following challenge with Pseudomonas syringae pv tomato DC3000 and the nonpathogenic mutant strain DC3000hrpA- allowed us to establish causal links between the activities of pathogen effectors and suppression of MTI and infer with high confidence a range of processes specifically targeted by effectors. Analysis of this information-rich data set with a range of computational tools provided insights into the earliest transcriptional events triggered by effector delivery, regulatory mechanisms recruited, and biological processes targeted. We show that the majority of genes contributing to disease or defense are induced within 6 h postinfection, significantly before pathogen multiplication. Suppression of chloroplast-associated genes is a rapid MAMP-triggered defense response, and suppression of genes involved in chromatin assembly and induction of ubiquitin-related genes coincide with pathogen-induced abscisic acid accumulation. Specific combinations of promoter motifs are engaged in fine-tuning the MTI response and active transcriptional suppression at specific promoter configurations by P. syringae. PMID:26566919

Transcriptional Dynamics Driving MAMP-Triggered Immunity and Pathogen Effector-Mediated Immunosuppression in Arabidopsis Leaves Following Infection with Pseudomonas syringae pv tomato DC3000.

PubMed

Lewis, Laura A; Polanski, Krzysztof; de Torres-Zabala, Marta; Jayaraman, Siddharth; Bowden, Laura; Moore, Jonathan; Penfold, Christopher A; Jenkins, Dafyd J; Hill, Claire; Baxter, Laura; Kulasekaran, Satish; Truman, William; Littlejohn, George; Prusinska, Justyna; Mead, Andrew; Steinbrenner, Jens; Hickman, Richard; Rand, David; Wild, David L; Ott, Sascha; Buchanan-Wollaston, Vicky; Smirnoff, Nick; Beynon, Jim; Denby, Katherine; Grant, Murray

2015-11-01

Transcriptional reprogramming is integral to effective plant defense. Pathogen effectors act transcriptionally and posttranscriptionally to suppress defense responses. A major challenge to understanding disease and defense responses is discriminating between transcriptional reprogramming associated with microbial-associated molecular pattern (MAMP)-triggered immunity (MTI) and that orchestrated by effectors. A high-resolution time course of genome-wide expression changes following challenge with Pseudomonas syringae pv tomato DC3000 and the nonpathogenic mutant strain DC3000hrpA- allowed us to establish causal links between the activities of pathogen effectors and suppression of MTI and infer with high confidence a range of processes specifically targeted by effectors. Analysis of this information-rich data set with a range of computational tools provided insights into the earliest transcriptional events triggered by effector delivery, regulatory mechanisms recruited, and biological processes targeted. We show that the majority of genes contributing to disease or defense are induced within 6 h postinfection, significantly before pathogen multiplication. Suppression of chloroplast-associated genes is a rapid MAMP-triggered defense response, and suppression of genes involved in chromatin assembly and induction of ubiquitin-related genes coincide with pathogen-induced abscisic acid accumulation. Specific combinations of promoter motifs are engaged in fine-tuning the MTI response and active transcriptional suppression at specific promoter configurations by P. syringae. © 2015 American Society of Plant Biologists. All rights reserved.

AutoDrug: fully automated macromolecular crystallography workflows for fragment-based drug discovery

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

Tsai, Yingssu; Stanford University, 333 Campus Drive, Mudd Building, Stanford, CA 94305-5080; McPhillips, Scott E.

New software has been developed for automating the experimental and data-processing stages of fragment-based drug discovery at a macromolecular crystallography beamline. A new workflow-automation framework orchestrates beamline-control and data-analysis software while organizing results from multiple samples. AutoDrug is software based upon the scientific workflow paradigm that integrates the Stanford Synchrotron Radiation Lightsource macromolecular crystallography beamlines and third-party processing software to automate the crystallography steps of the fragment-based drug-discovery process. AutoDrug screens a cassette of fragment-soaked crystals, selects crystals for data collection based on screening results and user-specified criteria and determines optimal data-collection strategies. It then collects and processes diffraction data,more » performs molecular replacement using provided models and detects electron density that is likely to arise from bound fragments. All processes are fully automated, i.e. are performed without user interaction or supervision. Samples can be screened in groups corresponding to particular proteins, crystal forms and/or soaking conditions. A single AutoDrug run is only limited by the capacity of the sample-storage dewar at the beamline: currently 288 samples. AutoDrug was developed in conjunction with RestFlow, a new scientific workflow-automation framework. RestFlow simplifies the design of AutoDrug by managing the flow of data and the organization of results and by orchestrating the execution of computational pipeline steps. It also simplifies the execution and interaction of third-party programs and the beamline-control system. Modeling AutoDrug as a scientific workflow enables multiple variants that meet the requirements of different user groups to be developed and supported. A workflow tailored to mimic the crystallography stages comprising the drug-discovery pipeline of CoCrystal Discovery Inc. has been deployed and successfully demonstrated. This workflow was run once on the same 96 samples that the group had examined manually and the workflow cycled successfully through all of the samples, collected data from the same samples that were selected manually and located the same peaks of unmodeled density in the resulting difference Fourier maps.« less

CENP-E Kinesin Interacts with SKAP Protein to Orchestrate Accurate Chromosome Segregation in Mitosis*

PubMed Central

Huang, Yuejia; Wang, Wenwen; Yao, Phil; Wang, Xiwei; Liu, Xing; Zhuang, Xiaoxuan; Yan, Feng; Zhou, Jinhua; Du, Jian; Ward, Tarsha; Zou, Hanfa; Zhang, Jiancun; Fang, Guowei; Ding, Xia; Dou, Zhen; Yao, Xuebiao

2012-01-01

Mitotic chromosome segregation is orchestrated by the dynamic interaction of spindle microtubules with the kinetochore. Although previous studies show that the mitotic kinesin CENP-E forms a link between attachment of the spindle microtubule to the kinetochore and the mitotic checkpoint signaling cascade, the molecular mechanism underlying dynamic kinetochore-microtubule interactions in mammalian cells remains elusive. Here, we identify a novel interaction between CENP-E and SKAP that functions synergistically in governing dynamic kinetochore-microtubule interactions. SKAP binds to the C-terminal tail of CENP-E in vitro and is essential for an accurate kinetochore-microtubule attachment in vivo. Immunoelectron microscopic analysis indicates that SKAP is a constituent of the kinetochore corona fibers of mammalian centromeres. Depletion of SKAP or CENP-E by RNA interference results in a dramatic reduction of inter-kinetochore tension, which causes chromosome mis-segregation with a prolonged delay in achieving metaphase alignment. Importantly, SKAP binds to microtubules in vitro, and this interaction is synergized by CENP-E. Based on these findings, we propose that SKAP cooperates with CENP-E to orchestrate dynamic kinetochore-microtubule interaction for faithful chromosome segregation. PMID:22110139

TRIO: Burst Buffer Based I/O Orchestration

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

Wang, Teng; Oral, H Sarp; Pritchard, Michael

The growing computing power on leadership HPC systems is often accompanied by ever-escalating failure rates. Checkpointing is a common defensive mechanism used by scientific applications for failure recovery. However, directly writing the large and bursty checkpointing dataset to parallel filesystem can incur significant I/O contention on storage servers. Such contention in turn degrades the raw bandwidth utilization of storage servers and prolongs the average job I/O time of concurrent applications. Recently burst buffer has been proposed as an intermediate layer to absorb the bursty I/O traffic from compute nodes to storage backend. But an I/O orchestration mechanism is still desiredmore » to efficiently move checkpointing data from bursty buffers to storage backend. In this paper, we propose a burst buffer based I/O orchestration framework, named TRIO, to intercept and reshape the bursty writes for better sequential write traffic to storage severs. Meanwhile, TRIO coordinates the flushing orders among concurrent burst buffers to alleviate the contention on storage server bandwidth. Our experimental results reveal that TRIO can deliver 30.5% higher bandwidth and reduce the average job I/O time by 37% on average for data-intensive applications in various checkpointing scenarios.« less

FOXP3 Orchestrates H4K16 Acetylation and H3K4 Tri-Methylation for Activation of Multiple Genes through Recruiting MOF and Causing Displacement of PLU-1

PubMed Central

Katoh, Hiroto; Qin, Zhaohui S.; Liu, Runhua; Wang, Lizhong; Li, Weiquan; Li, Xiangzhi; Wu, Lipeng; Du, Zhanwen; Lyons, Robert; Liu, Chang-Gong; Liu, Xiuping; Dou, Yali; Zheng, Pan; Liu, Yang

2011-01-01

SUMMARY Both H4K16 acetylation and H3K4 tri-methylation are required for gene activation. However, it is still largely unclear how these modifications are orchestrated by transcriptional factors. Here we analyzed the mechanism of the transcriptional activation by FOXP3, an X-linked suppressor of autoimmune diseases and cancers. FOXP3 binds near transcriptional start sites of its target genes. By recruiting MOF and displacing histone H3K4 demethylase PLU-1, FOXP3 increases both H4K16 acetylation and H3K4 tri-methylation at the FOXP3-associated chromatins of multiple FOXP3-activated genes. RNAi-mediated silencing of MOF reduced both gene activation and tumor suppression by FOXP3, while both somatic mutations in clinical cancer samples and targeted mutation of FOXP3 in mouse prostate epithelial disrupted nuclear localization of MOF. Our data demonstrate a pull-push model in which a single transcription factor orchestrates two epigenetic alterations necessary for gene activation and provide a mechanism for somatic inactivation of the FOXP3 protein function in cancer cells. PMID:22152480

Multimedia content analysis and indexing: evaluation of a distributed and scalable architecture

NASA Astrophysics Data System (ADS)

Mandviwala, Hasnain; Blackwell, Scott; Weikart, Chris; Van Thong, Jean-Manuel

2003-11-01

Multimedia search engines facilitate the retrieval of documents from large media content archives now available via intranets and the Internet. Over the past several years, many research projects have focused on algorithms for analyzing and indexing media content efficiently. However, special system architectures are required to process large amounts of content from real-time feeds or existing archives. Possible solutions include dedicated distributed architectures for analyzing content rapidly and for making it searchable. The system architecture we propose implements such an approach: a highly distributed and reconfigurable batch media content analyzer that can process media streams and static media repositories. Our distributed media analysis application handles media acquisition, content processing, and document indexing. This collection of modules is orchestrated by a task flow management component, exploiting data and pipeline parallelism in the application. A scheduler manages load balancing and prioritizes the different tasks. Workers implement application-specific modules that can be deployed on an arbitrary number of nodes running different operating systems. Each application module is exposed as a web service, implemented with industry-standard interoperable middleware components such as Microsoft ASP.NET and Sun J2EE. Our system architecture is the next generation system for the multimedia indexing application demonstrated by www.speechbot.com. It can process large volumes of audio recordings with minimal support and maintenance, while running on low-cost commodity hardware. The system has been evaluated on a server farm running concurrent content analysis processes.

Cell remodeling and subtilase gene expression in the actinorhizal plant Discaria trinervis highlight host orchestration of intercellular Frankia colonization.

PubMed

Fournier, Joëlle; Imanishi, Leandro; Chabaud, Mireille; Abdou-Pavy, Iltaf; Genre, Andrea; Brichet, Lukas; Lascano, Hernán Ramiro; Muñoz, Nacira; Vayssières, Alice; Pirolles, Elodie; Brottier, Laurent; Gherbi, Hassen; Hocher, Valérie; Svistoonoff, Sergio; Barker, David G; Wall, Luis G

2018-05-23

Nitrogen-fixing filamentous Frankia colonize the root tissues of its actinorhizal host Discaria trinervis via an exclusively intercellular pathway. Here we present studies aimed at uncovering mechanisms associated with this little-researched mode of root entry, and in particular the extent to which the host plant is an active partner during this process. Detailed characterization of the expression patterns of infection-associated actinorhizal host genes has provided valuable tools to identify intercellular infection sites, thus allowing in vivo confocal microscopic studies of the early stages of Frankia colonization. The subtilisin-like serine protease gene Dt12, as well as its Casuarina glauca homolog Cg12, are specifically expressed at sites of Frankia intercellular colonization of D. trinervis outer root tissues. This is accompanied by nucleo-cytoplasmic reorganization in the adjacent host cells and major remodeling of the intercellular apoplastic compartment. These findings lead us to propose that the actinorhizal host plays a major role in modifying both the size and composition of the intercellular apoplast in order to accommodate the filamentous microsymbiont. The implications of these findings are discussed in the light of the analogies that can be made with the orchestrating role of host legumes during intracellular root hair colonization by nitrogen-fixing rhizobia. © 2018 The Authors New Phytologist © 2018 New Phytologist Trust.

Concert halls with strong lateral reflections enhance musical dynamics.

PubMed

Pätynen, Jukka; Tervo, Sakari; Robinson, Philip W; Lokki, Tapio

2014-03-25

One of the most thrilling cultural experiences is to hear live symphony-orchestra music build up from a whispering passage to a monumental fortissimo. The impact of such a crescendo has been thought to depend only on the musicians' skill, but here we show that interactions between the concert-hall acoustics and listeners' hearing also play a major role in musical dynamics. These interactions contribute to the shoebox-type concert hall's established success, but little prior research has been devoted to dynamic expression in this three-part transmission chain as a complete system. More forceful orchestral playing disproportionately excites high frequency harmonics more than those near the note's fundamental. This effect results in not only more sound energy, but also a different tone color. The concert hall transmits this sound, and the room geometry defines from which directions acoustic reflections arrive at the listener. Binaural directional hearing emphasizes high frequencies more when sound arrives from the sides of the head rather than from the median plane. Simultaneously, these same frequencies are emphasized by higher orchestral-playing dynamics. When the room geometry provides reflections from these directions, the perceived dynamic range is enhanced. Current room-acoustic evaluation methods assume linear behavior and thus neglect this effect. The hypothesis presented here is that the auditory excitation by reflections is emphasized with an orchestra forte most in concert halls with strong lateral reflections. The enhanced dynamic range provides an explanation for the success of rectangularly shaped concert-hall geometry.

A General and Mild Approach to Controllable Preparation of Manganese-Based Micro- and Nanostructured Bars for High Performance Lithium-Ion Batteries.

PubMed

Ma, Guo; Li, Sheng; Zhang, Weixin; Yang, Zeheng; Liu, Shulin; Fan, Xiaoming; Chen, Fei; Tian, Yuan; Zhang, Weibo; Yang, Shihe; Li, Mei

2016-03-07

One-dimensional (1D) micro- and nanostructured electrode materials with controllable phase and composition are appealing materials for use in lithium-ion batteries with high energy and power densities, but they are challenging to prepare. Herein, a novel ethanol-water mediated co-precipitation method by a chimie douce route (synthesis conducted under mild conditions) has been exploited to selectively prepare an extensive series of manganese-based electrode materials, manifesting the considerable generalizability and efficacy of the method. Moreover, by simply tuning the mixed solvent and reagents, transition metal oxide bars with differing aspect ratios and compositions were prepared with an unprecedented uniformity. Application prospects are demonstrated by Li-rich 0.5 Li2 MnO3 ⋅0.5 LiNi1/3 Co1/3 Mn1/3 O2 bars, which demonstrate excellent reversible capacity and rate capability thanks to the steerable nature of the synthesis and material quality. This work opens a new route to 1D micro- and nanostructured materials by customizing the precipitating solvent to orchestrate the crystallization process. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Developmental expression of Drosophila Wiskott-Aldrich Syndrome family proteins

PubMed Central

Rodriguez-Mesa, Evelyn; Abreu-Blanco, Maria Teresa; Rosales-Nieves, Alicia E.; Parkhurst, Susan M.

2012-01-01

Background Wiskott-Aldrich Syndrome (WASP) family proteins participate in many cellular processes involving rearrangements of the actin cytoskeleton. To the date, four WASP subfamily members have been described in Drosophila: Wash, WASp, SCAR, and Whamy. Wash, WASp, and SCAR are essential during early Drosophila development where they function in orchestrating cytoplasmic events including membrane-cytoskeleton interactions. A mutant for Whamy has not yet been reported. Results We generated monoclonal antibodies that are specific to Drosophila Wash, WASp, SCAR, and Whamy, and use these to describe their spatial and temporal localization patterns. Consistent with the importance of WASP family proteins in flies, we find that Wash, WASp, SCAR, and Whamy are dynamically expressed throughout oogenesis and embryogenesis. For example, we find that Wash accumulates at the oocyte cortex. WASp is highly expressed in the PNS, while SCAR is the most abundantly expressed in the CNS. Whamy exhibits an asymmetric subcellular localization that overlaps with mitochondria and is highly expressed in muscle. Conclusion All four WASP family members show specific expression patterns, some of which reflect their previously known roles and others revealing new potential functions. The monoclonal antibodies developed offer valuable new tools to investigate how WASP family proteins regulate actin cytoskeleton dynamics. PMID:22275148

Creative thinking as orchestrated by semantic processing vs. cognitive control brain networks.

PubMed

Abraham, Anna

2014-01-01

Creativity is primarily investigated within the neuroscientific perspective as a unitary construct. While such an approach is beneficial when trying to infer the general picture regarding creativity and brain function, it is insufficient if the objective is to uncover the information processing brain mechanisms by which creativity occurs. As creative thinking emerges through the dynamic interplay between several cognitive processes, assessing the neural correlates of these operations would enable the development and characterization of an information processing framework from which to better understand this complex ability. This article focuses on two aspects of creative cognition that are central to generating original ideas. "Conceptual expansion" refers to the ability to widen one's conceptual structures to include unusual or novel associations, while "overcoming knowledge constraints" refers to our ability to override the constraining influence imposed by salient or pertinent knowledge when trying to be creative. Neuroimaging and neuropsychological evidence is presented to illustrate how semantic processing and cognitive control networks in the brain differentially modulate these critical facets of creative cognition.

An automated and integrated framework for dust storm detection based on ogc web processing services

NASA Astrophysics Data System (ADS)

Xiao, F.; Shea, G. Y. K.; Wong, M. S.; Campbell, J.

2014-11-01

Dust storms are known to have adverse effects on public health. Atmospheric dust loading is also one of the major uncertainties in global climatic modelling as it is known to have a significant impact on the radiation budget and atmospheric stability. The complexity of building scientific dust storm models is coupled with the scientific computation advancement, ongoing computing platform development, and the development of heterogeneous Earth Observation (EO) networks. It is a challenging task to develop an integrated and automated scheme for dust storm detection that combines Geo-Processing frameworks, scientific models and EO data together to enable the dust storm detection and tracking processes in a dynamic and timely manner. This study develops an automated and integrated framework for dust storm detection and tracking based on the Web Processing Services (WPS) initiated by Open Geospatial Consortium (OGC). The presented WPS framework consists of EO data retrieval components, dust storm detecting and tracking component, and service chain orchestration engine. The EO data processing component is implemented based on OPeNDAP standard. The dust storm detecting and tracking component combines three earth scientific models, which are SBDART model (for computing aerosol optical depth (AOT) of dust particles), WRF model (for simulating meteorological parameters) and HYSPLIT model (for simulating the dust storm transport processes). The service chain orchestration engine is implemented based on Business Process Execution Language for Web Service (BPEL4WS) using open-source software. The output results, including horizontal and vertical AOT distribution of dust particles as well as their transport paths, were represented using KML/XML and displayed in Google Earth. A serious dust storm, which occurred over East Asia from 26 to 28 Apr 2012, is used to test the applicability of the proposed WPS framework. Our aim here is to solve a specific instance of a complex EO data and scientific model integration problem by using a framework and scientific workflow approach together. The experimental result shows that this newly automated and integrated framework can be used to give advance near real-time warning of dust storms, for both environmental authorities and public. The methods presented in this paper might be also generalized to other types of Earth system models, leading to improved ease of use and flexibility.

High-throughput neuroimaging-genetics computational infrastructure

PubMed Central

Dinov, Ivo D.; Petrosyan, Petros; Liu, Zhizhong; Eggert, Paul; Hobel, Sam; Vespa, Paul; Woo Moon, Seok; Van Horn, John D.; Franco, Joseph; Toga, Arthur W.

2014-01-01

Many contemporary neuroscientific investigations face significant challenges in terms of data management, computational processing, data mining, and results interpretation. These four pillars define the core infrastructure necessary to plan, organize, orchestrate, validate, and disseminate novel scientific methods, computational resources, and translational healthcare findings. Data management includes protocols for data acquisition, archival, query, transfer, retrieval, and aggregation. Computational processing involves the necessary software, hardware, and networking infrastructure required to handle large amounts of heterogeneous neuroimaging, genetics, clinical, and phenotypic data and meta-data. Data mining refers to the process of automatically extracting data features, characteristics and associations, which are not readily visible by human exploration of the raw dataset. Result interpretation includes scientific visualization, community validation of findings and reproducible findings. In this manuscript we describe the novel high-throughput neuroimaging-genetics computational infrastructure available at the Institute for Neuroimaging and Informatics (INI) and the Laboratory of Neuro Imaging (LONI) at University of Southern California (USC). INI and LONI include ultra-high-field and standard-field MRI brain scanners along with an imaging-genetics database for storing the complete provenance of the raw and derived data and meta-data. In addition, the institute provides a large number of software tools for image and shape analysis, mathematical modeling, genomic sequence processing, and scientific visualization. A unique feature of this architecture is the Pipeline environment, which integrates the data management, processing, transfer, and visualization. Through its client-server architecture, the Pipeline environment provides a graphical user interface for designing, executing, monitoring validating, and disseminating of complex protocols that utilize diverse suites of software tools and web-services. These pipeline workflows are represented as portable XML objects which transfer the execution instructions and user specifications from the client user machine to remote pipeline servers for distributed computing. Using Alzheimer's and Parkinson's data, we provide several examples of translational applications using this infrastructure1. PMID:24795619

Regulation of wound healing and fibrosis by hypoxia and hypoxia-inducible factor-1.

PubMed

Ruthenborg, Robin J; Ban, Jae-Jun; Wazir, Anum; Takeda, Norihiko; Kim, Jung-Whan

2014-09-01

Wound healing is a complex multi-step process that requires spatial and temporal orchestration of cellular and non-cellular components. Hypoxia is one of the prominent microenvironmental factors in tissue injury and wound healing. Hypoxic responses, mainly mediated by a master transcription factor of oxygen homeostasis, hypoxia-inducible factor-1 (HIF-1), have been shown to be critically involved in virtually all processes of wound healing and remodeling. Yet, mechanisms underlying hypoxic regulation of wound healing are still poorly understood. Better understanding of how the wound healing process is regulated by the hypoxic microenvironment and HIF-1 signaling pathway will provide insight into the development of a novel therapeutic strategy for impaired wound healing conditions such as diabetic wound and fibrosis. In this review, we will discuss recent studies illuminating the roles of HIF-1 in physiologic and pathologic wound repair and further, the therapeutic potentials of HIF-1 stabilization or inhibition.

microRNA expression in the neural retina: Focus on Müller glia.

PubMed

Quintero, Heberto; Lamas, Mónica

2018-03-01

The neural retina hosts a unique specialized type of macroglial cell that not only preserves retinal homeostasis, function, and integrity but also may serve as a source of new neurons during regenerative processes: the Müller cell. Precise microRNA-driven mechanisms of gene regulation impel and direct the processes of Müller glia lineage acquisition from retinal progenitors during development, the triggering of their response to retinal degeneration and, in some cases, Müller cell reprogramming and regenerative events. In this review we survey the recent reports describing, through functional assays, the regulatory role of microRNAs in Müller cell physiology, differentiation potential, and retinal pathology. We discuss also the evidence based on expression analysis that points out the relevance of a Müller glia-specific microRNA signature that would orchestrate these processes. © 2017 Wiley Periodicals, Inc.

Building asynchronous geospatial processing workflows with web services

NASA Astrophysics Data System (ADS)

Zhao, Peisheng; Di, Liping; Yu, Genong

2012-02-01

Geoscience research and applications often involve a geospatial processing workflow. This workflow includes a sequence of operations that use a variety of tools to collect, translate, and analyze distributed heterogeneous geospatial data. Asynchronous mechanisms, by which clients initiate a request and then resume their processing without waiting for a response, are very useful for complicated workflows that take a long time to run. Geospatial contents and capabilities are increasingly becoming available online as interoperable Web services. This online availability significantly enhances the ability to use Web service chains to build distributed geospatial processing workflows. This paper focuses on how to orchestrate Web services for implementing asynchronous geospatial processing workflows. The theoretical bases for asynchronous Web services and workflows, including asynchrony patterns and message transmission, are examined to explore different asynchronous approaches to and architecture of workflow code for the support of asynchronous behavior. A sample geospatial processing workflow, issued by the Open Geospatial Consortium (OGC) Web Service, Phase 6 (OWS-6), is provided to illustrate the implementation of asynchronous geospatial processing workflows and the challenges in using Web Services Business Process Execution Language (WS-BPEL) to develop them.

Family routines within the ecological niche: an analysis of the psychological well-being of U.S. caregivers of children with disabilities

PubMed Central

Larson, Elizabeth; Miller-Bishoff, Thomas

2014-01-01

Using mixed methods, this study examined the relationship of caregivers of children with disabilities’ psychological well-being (PWB) and their orchestration of daily routines within their ecological niche. Thirty-nine U.S. caregivers completed in-depth interviews, PWB Scales, and Family Time and Routines Index (FTRI). We used a multi-step analysis. Interview data was coded and vignettes created without knowledge of PWB and FTRI ratings. Next, the relationship of quantitative measures was analyzed. Four groups were created using FTRI-extent and PWB means: (1) low routine-low PWB, (2) low routine-high PWB, (3) high routine-low PWB, and (4) high routine-high PWB. We examined qualitative differences in key features between groups. Findings: Total PWB and FTRI scores were not significantly correlated, PWB Purpose in Life and FTRI-extent scores were moderately positively correlated, and PWB Environmental Mastery and FTRI-extent correlation approached significance. Qualitative findings describe caregivers’ structuring of routines, intensity of oversight, support in routines, management of dinner, paid work, and needs for respite. The four groups differed in paid work, household support, degree the child could self-occupy, Environmental Mastery, and opportunities to recuperate. Caregivers with higher levels of well-being and more regular routines did paid work, had supportive spouses, had children who more often could follow routines, had higher Environmental Mastery, could orchestrate a family meal, and had breaks from care in either work or leisure. All Native American caregivers and Mexican American caregivers with spouses were in the high routine-high PWB group. Insight into this complex negotiation between family members within daily routines may provide practitioners a better understanding of how to work within family circles to foster therapeutic alliances, identify focused intervention targets, and promote positive family wide outcomes. PMID:24910625

H2O2 from the oxidative burst orchestrates the plant hypersensitive disease resistance response.

PubMed

Levine, A; Tenhaken, R; Dixon, R; Lamb, C

1994-11-18

Microbial elicitors or attempted infection with an avirulent pathogen strain causes the rapid production of reactive oxygen intermediates. We report here that H2O2 from this oxidative burst not only drives the cross-linking of cell wall structural proteins, but also functions as a local trigger of programmed death in challenged cells and as a diffusible signal for the induction in adjacent cells of genes encoding cellular protectants such as glutathione S-transferase and glutathione peroxidase. Thus, H2O2 from the oxidative burst plays a key role in the orchestration of a localized hypersensitive response during the expression of plant disease resistance.

Orchestrating liver development.

PubMed

Gordillo, Miriam; Evans, Todd; Gouon-Evans, Valerie

2015-06-15

The liver is a central regulator of metabolism, and liver failure thus constitutes a major health burden. Understanding how this complex organ develops during embryogenesis will yield insights into how liver regeneration can be promoted and how functional liver replacement tissue can be engineered. Recent studies of animal models have identified key signaling pathways and complex tissue interactions that progressively generate liver progenitor cells, differentiated lineages and functional tissues. In addition, progress in understanding how these cells interact, and how transcriptional and signaling programs precisely coordinate liver development, has begun to elucidate the molecular mechanisms underlying this complexity. Here, we review the lineage relationships, signaling pathways and transcriptional programs that orchestrate hepatogenesis. © 2015. Published by The Company of Biologists Ltd.

Directivity measurements of the violin during performance

NASA Astrophysics Data System (ADS)

Hardy, Jean-François; Migneron, Jean-Gabriel

2005-04-01

Many studies have shown that directivity of musical instruments is significant for the perceived sound within the hall and for performer's ease of hearing each other. The directivity patterns explain in part the differences between many common or special orchestral stage plots. Measurements of the violin's directivity have been performed using an acoustical intensimetry procedure. The precise directivity characteristics of isolated tones have been compared with the mean directivity resulting from performance of four extracts chosen among the orchestral repertoire. Results, which were measured in both horizontal and vertical planes, show interesting differences between the average directivity of each test. They lead to links with few important distinctions in the traditional violin's positions inside the orchestra.

Overexpression of CaAPX Induces Orchestrated Reactive Oxygen Scavenging and Enhances Cold and Heat Tolerances in Tobacco

PubMed Central

Wang, Jiangying; Wu, Bin; Fan, Zhengqi; Li, Xinlei; Ni, Sui

2017-01-01

Ascorbate peroxidase (APX) acts indispensably in synthesizing L-ascorbate (AsA) which is pivotal to plant stress tolerance by detoxifying reactive oxygen species (ROS). Enhanced activity of APX has been shown to be a key step for genetic engineering of improving plant tolerance. However it needs a deeper understanding on the maintenance of cellular ROS homeostasis in response to stress. In this study, we identified and characterized an APX (CaAPX) gene from Camellia azalea. Quantitative real-time PCR (qRT-PCR) analysis showed that CaAPX was expressed in all tissues and peaked in immature green fruits; the expression levels were significantly upregulated upon cold and hot stresses. Transgenic plants displayed marked enhancements of tolerance under both cold and heat treatments, and plant growth was correlated with CaAPX expression levels. Furthermore, we monitored the activities of several ROS-scavenging enzymes including Cu/Zn-SOD, CAT, DHAR, and MDHAR, and we showed that stress tolerance was synchronized with elevated activities of ROS-scavenging. Moreover, gene expression analysis of ROS-scavenging enzymes revealed a role of CaAPX to orchestrate ROS signaling in response to temperature stresses. Overall, this study presents a comprehensive characterization of cellular response related to CaAPX expression and provides insights to breed crops with high temperature tolerances. PMID:28386551

Overexpression of CaAPX Induces Orchestrated Reactive Oxygen Scavenging and Enhances Cold and Heat Tolerances in Tobacco.

PubMed

Wang, Jiangying; Wu, Bin; Yin, Hengfu; Fan, Zhengqi; Li, Xinlei; Ni, Sui; He, Libo; Li, Jiyuan

2017-01-01

Ascorbate peroxidase (APX) acts indispensably in synthesizing L-ascorbate (AsA) which is pivotal to plant stress tolerance by detoxifying reactive oxygen species (ROS). Enhanced activity of APX has been shown to be a key step for genetic engineering of improving plant tolerance. However it needs a deeper understanding on the maintenance of cellular ROS homeostasis in response to stress. In this study, we identified and characterized an APX ( CaAPX ) gene from Camellia azalea . Quantitative real-time PCR (qRT-PCR) analysis showed that CaAPX was expressed in all tissues and peaked in immature green fruits; the expression levels were significantly upregulated upon cold and hot stresses. Transgenic plants displayed marked enhancements of tolerance under both cold and heat treatments, and plant growth was correlated with CaAPX expression levels. Furthermore, we monitored the activities of several ROS-scavenging enzymes including Cu/Zn-SOD , CAT , DHAR , and MDHAR , and we showed that stress tolerance was synchronized with elevated activities of ROS-scavenging. Moreover, gene expression analysis of ROS-scavenging enzymes revealed a role of CaAPX to orchestrate ROS signaling in response to temperature stresses. Overall, this study presents a comprehensive characterization of cellular response related to CaAPX expression and provides insights to breed crops with high temperature tolerances.

Remodeling in bone without osteocytes: Billfish challenge bone structure–function paradigms

PubMed Central

Atkins, Ayelet; Dean, Mason N.; Habegger, Maria Laura; Motta, Phillip J.; Ofer, Lior; Repp, Felix; Shipov, Anna; Weiner, Steve; Currey, John D.; Shahar, Ron

2014-01-01

A remarkable property of tetrapod bone is its ability to detect and remodel areas where damage has accumulated through prolonged use. This process, believed vital to the long-term health of bone, is considered to be initiated and orchestrated by osteocytes, cells within the bone matrix. It is therefore surprising that most extant fishes (neoteleosts) lack osteocytes, suggesting their bones are not constantly repaired, although many species exhibit long lives and high activity levels, factors that should induce considerable fatigue damage with time. Here, we show evidence for active and intense remodeling occurring in the anosteocytic, elongated rostral bones of billfishes (e.g., swordfish, marlins). Despite lacking osteocytes, this tissue exhibits a striking resemblance to the mature bone of large mammals, bearing structural features (overlapping secondary osteons) indicating intensive tissue repair, particularly in areas where high loads are expected. Billfish osteons are an order of magnitude smaller in diameter than mammalian osteons, however, implying that the nature of damage in this bone may be different. Whereas billfish bone material is as stiff as mammalian bone (unlike the bone of other fishes), it is able to withstand much greater strains (relative deformations) before failing. Our data show that fish bone can exhibit far more complex structure and physiology than previously known, and is apparently capable of localized repair even without the osteocytes believed essential for this process. These findings challenge the unique and primary role of osteocytes in bone remodeling, a basic tenet of bone biology, raising the possibility of an alternative mechanism driving this process. PMID:25331870

Caspases and Kinases in a Death Grip

PubMed Central

Kurokawa, Manabu; Kornbluth, Sally

2011-01-01

The complex process of apoptosis is orchestrated by caspases, a family of cysteine proteases with unique substrate specificities. Accumulating evidence suggests that cell death pathways are finely tuned by multiple signaling events, including direct phosphorylation of caspases, whereas kinases are often substrates of active caspases. Importantly, caspase-mediated cleavage of kinases can terminate prosurvival signaling or generate proapoptotic peptide fragments that help to execute the death program and facilitate packaging of the dying cells. Here, we review caspases as kinase substrates and kinases as caspase substrates and discuss how the balance between cell survival and cell death can be shifted through crosstalk between these two enzyme families. PMID:19737514

Noncoding RNAs and the control of signalling via nuclear receptor regulation in health and disease.

PubMed

Cathcart, Paul; Lucchesi, Walter; Ottaviani, Silvia; De Giorgio, Alex; Krell, Jonathan; Stebbing, Justin; Castellano, Leandro

2015-08-01

Nuclear receptors belong to a superfamily of proteins that play central roles in human biology, orchestrating a large variety of biological functions in both health and disease. Understanding the interactions and regulatory pathways of NRs will allow development of potential therapeutic interventions for a multitude of disease processes. Non-coding RNAs have recently been discovered to have significant interactions with NR signalling pathways via a variety of biological connections. This review summarises the known interactions between ncRNAs and the NR superfamily in health, embryogenesis and a plethora of human diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Functional microdomains in bacterial membranes.

PubMed

López, Daniel; Kolter, Roberto

2010-09-01

The membranes of eukaryotic cells harbor microdomains known as lipid rafts that contain a variety of signaling and transport proteins. Here we show that bacterial membranes contain microdomains functionally similar to those of eukaryotic cells. These membrane microdomains from diverse bacteria harbor homologs of Flotillin-1, a eukaryotic protein found exclusively in lipid rafts, along with proteins involved in signaling and transport. Inhibition of lipid raft formation through the action of zaragozic acid--a known inhibitor of squalene synthases--impaired biofilm formation and protein secretion but not cell viability. The orchestration of physiological processes in microdomains may be a more widespread feature of membranes than previously appreciated.

Molecular underpinnings of prefrontal cortex development in rodents provide insights into the etiology of neurodevelopmental disorders.

PubMed

Schubert, D; Martens, G J M; Kolk, S M

2015-07-01

The prefrontal cortex (PFC), seat of the highest-order cognitive functions, constitutes a conglomerate of highly specialized brain areas and has been implicated to have a role in the onset and installation of various neurodevelopmental disorders. The development of a properly functioning PFC is directed by transcription factors, guidance cues and other regulatory molecules and requires the intricate and temporal orchestration of a number of developmental processes. Disturbance or failure of any of these processes causing neurodevelopmental abnormalities within the PFC may contribute to several of the cognitive deficits seen in patients with neurodevelopmental disorders. In this review, we elaborate on the specific processes underlying prefrontal development, such as induction and patterning of the prefrontal area, proliferation, migration and axonal guidance of medial prefrontal progenitors, and their eventual efferent and afferent connections. We furthermore integrate for the first time the available knowledge from genome-wide studies that have revealed genes linked to neurodevelopmental disorders with experimental molecular evidence in rodents. The integrated data suggest that the pathogenic variants in the neurodevelopmental disorder-associated genes induce prefrontal cytoarchitectonical impairments. This enhances our understanding of the molecular mechanisms of prefrontal (mis)development underlying the four major neurodevelopmental disorders in humans, that is, intellectual disability, autism spectrum disorders, attention deficit hyperactivity disorder and schizophrenia, and may thus provide clues for the development of novel therapies.

Non-thermal plasma activates human keratinocytes by stimulation of antioxidant and phase II pathways.

PubMed

Schmidt, Anke; Dietrich, Stephan; Steuer, Anna; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Masur, Kai; Wende, Kristian

2015-03-13

Non-thermal atmospheric pressure plasma provides a novel therapeutic opportunity to control redox-based processes, e.g. wound healing, cancer, and inflammatory diseases. By spatial and time-resolved delivery of reactive oxygen and nitrogen species, it allows stimulation or inhibition of cellular processes in biological systems. Our data show that both gene and protein expression is highly affected by non-thermal plasma. Nuclear factor erythroid-related factor 2 (NRF2) and phase II enzyme pathway components were found to act as key controllers orchestrating the cellular response in keratinocytes. Additionally, glutathione metabolism, which is a marker for NRF2-related signaling events, was affected. Among the most robustly increased genes and proteins, heme oxygenase 1, NADPH-quinone oxidoreductase 1, and growth factors were found. The roles of NRF2 targets, investigated by siRNA silencing, revealed that NRF2 acts as an important switch for sensing oxidative stress events. Moreover, the influence of non-thermal plasma on the NRF2 pathway prepares cells against exogenic noxae and increases their resilience against oxidative species. Via paracrine mechanisms, distant cells benefit from cell-cell communication. The finding that non-thermal plasma triggers hormesis-like processes in keratinocytes facilitates the understanding of plasma-tissue interaction and its clinical application. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Examining Teachers' Instructional Moves Aimed at Developing Students' Ideas and Questions in Learner-Centered Science Classrooms

NASA Astrophysics Data System (ADS)

Harris, Christopher J.; Phillips, Rachel S.; Penuel, William R.

2012-11-01

Prior research has shown that orchestrating scientific discourse in classrooms is difficult and takes a great deal of effort on the part of teachers. In this study, we examined teachers' instructional moves to elicit and develop students' ideas and questions as they orchestrated discourse with their fifth grade students during a learner-centered environmental biology unit. The unit materials included features meant to support teachers in eliciting and working with students' ideas and questions as a source for student-led investigations. We present three contrasting cases of teachers to highlight evidence that shows teachers' differing strategies for eliciting students' ideas and questions, and for developing their ideas, questions and questioning skills. Results from our cross case analysis provide insight into the ways in which teachers' enactments enabled them to work with students' ideas and questions to help advance learning. Consistent with other studies, we found that teachers could readily elicit ideas and questions but experienced challenges in helping students develop them. Findings suggest a need for more specified supports, such as specific discourse strategies, to help teachers attend to student thinking. We explore implications for curricular tools and discuss a need for more examples of effective discourse moves for use by teachers in orchestrating scientific discourse.

The roles of cannabinoid and dopamine receptor systems in neural emotional learning circuits: implications for schizophrenia and addiction.

PubMed

Laviolette, S R; Grace, A A

2006-07-01

Cannabinoids represent one of the most widely used hallucinogenic drugs and induce profound alterations in sensory perception and emotional processing. Similarly, the dopamine (DA) neurotransmitter system is critical for the central processing of emotion and motivation. Functional disturbances in either of these neurotransmitter systems are well-established correlates of the psychopathological symptoms and behavioral manifestations observed in addiction and schizophrenia. Increasing evidence from the anatomical, pharmacological and behavioral neuroscience fields points to complex functional interactions between these receptor systems at the anatomical, pharmacological and neural systems levels. An important question relates to whether these systems act in an orchestrated manner to produce the emotional processing and sensory perception deficits underlying addiction and schizophrenia. This review describes evidence for functional neural interactions between cannabinoid and DA receptor systems and how disturbances in this neural circuitry may underlie the aberrant emotional learning and processing observed in disorders such as addiction and schizophrenia.

Weighted Ensemble Simulation: Review of Methodology, Applications, and Software.

PubMed

Zuckerman, Daniel M; Chong, Lillian T

2017-05-22

The weighted ensemble (WE) methodology orchestrates quasi-independent parallel simulations run with intermittent communication that can enhance sampling of rare events such as protein conformational changes, folding, and binding. The WE strategy can achieve superlinear scaling-the unbiased estimation of key observables such as rate constants and equilibrium state populations to greater precision than would be possible with ordinary parallel simulation. WE software can be used to control any dynamics engine, such as standard molecular dynamics and cell-modeling packages. This article reviews the theoretical basis of WE and goes on to describe successful applications to a number of complex biological processes-protein conformational transitions, (un)binding, and assembly processes, as well as cell-scale processes in systems biology. We furthermore discuss the challenges that need to be overcome in the next phase of WE methodological development. Overall, the combined advances in WE methodology and software have enabled the simulation of long-timescale processes that would otherwise not be practical on typical computing resources using standard simulation.

Malondialdehyde epitopes as targets of immunity and the implications for atherosclerosis

PubMed Central

Binder, Christoph J.

2018-01-01

Accumulating evidence suggests that oxidation-specific epitopes (OSEs) constitute a novel class of damage-associated molecular patterns (DAMPs) generated during high oxidative stress but also in the physiological process of apoptosis. To deal with the potentially harmful consequences of such epitopes, the immune system has developed several mechanisms to protect from OSEs and to orchestrate their clearance, including IgM natural antibodies and both cellular and membrane-bound receptors. Here, we focus on malondialdehyde (MDA) epitopes as prominent examples of OSEs that trigger both innate and adaptive immune responses. First, we review the mechanism of MDA generation, the different types of adducts on various biomolecules and provide relevant examples for physiological carriers of MDA such as apoptotic cells, microvesicles (MV) or oxidized low-density lipoproteins (LDL). Based on recent insights, we argue that MDA epitopes contribute to the maintenance of homeostatic functions by acting as markers of elevated oxidative stress and tissue damage. We discuss multiple lines of evidence that MDA epitopes are pro-inflammatory and thus important targets of innate and adaptive immune responses. Finally, we illustrate the relevance of MDA epitopes in human pathologies by describing their capacity to drive inflammatory processes in atherosclerosis and highlighting protective mechanisms of immunity that could be exploited for therapeutic purposes. PMID:27235680

Spatial and temporal transcriptome changes occurring during flower opening and senescence of the ephemeral hibiscus flower, Hibiscus rosa-sinensis

PubMed Central

Trivellini, Alice; Cocetta, Giacomo; Hunter, Donald A.; Vernieri, Paolo; Ferrante, Antonio

2016-01-01

Flowers are complex systems whose vegetative and sexual structures initiate and die in a synchronous manner. The rapidity of this process varies widely in flowers, with some lasting for months while others such as Hibiscus rosa-sinensis survive for only a day. The genetic regulation underlying these differences is unclear. To identify key genes and pathways that coordinate floral organ senescence of ephemeral flowers, we identified transcripts in H. rosa-sinensis floral organs by 454 sequencing. During development, 2053 transcripts increased and 2135 decreased significantly in abundance. The senescence of the flower was associated with increased abundance of many hydrolytic genes, including aspartic and cysteine proteases, vacuolar processing enzymes, and nucleases. Pathway analysis suggested that transcripts altering significantly in abundance were enriched in functions related to cell wall-, aquaporin-, light/circadian clock-, autophagy-, and calcium-related genes. Finding enrichment in light/circadian clock-related genes fits well with the observation that hibiscus floral development is highly synchronized with light and the hypothesis that ageing/senescence of the flower is orchestrated by a molecular clock. Further study of these genes will provide novel insight into how the molecular clock is able to regulate the timing of programmed cell death in tissues. PMID:27591432

Correlated mRNAs and miRNAs from co-expression and regulatory networks affect porcine muscle and finally meat properties.

PubMed

Ponsuksili, Siriluck; Du, Yang; Hadlich, Frieder; Siengdee, Puntita; Murani, Eduard; Schwerin, Manfred; Wimmers, Klaus

2013-08-05

Physiological processes aiding the conversion of muscle to meat involve many genes associated with muscle structure and metabolic processes. MicroRNAs regulate networks of genes to orchestrate cellular functions, in turn regulating phenotypes. We applied weighted gene co-expression network analysis to identify co-expression modules that correlated to meat quality phenotypes and were highly enriched for genes involved in glucose metabolism, response to wounding, mitochondrial ribosome, mitochondrion, and extracellular matrix. Negative correlation of miRNA with mRNA and target prediction were used to select transcripts out of the modules of trait-associated mRNAs to further identify those genes that are correlated with post mortem traits. Porcine muscle co-expression transcript networks that correlated to post mortem traits were identified. The integration of miRNA and mRNA expression analyses, as well as network analysis, enabled us to interpret the differentially-regulated genes from a systems perspective. Linking co-expression networks of transcripts and hierarchically organized pairs of miRNAs and mRNAs to meat properties yields new insight into several biological pathways underlying phenotype differences. These pathways may also be diagnostic for many myopathies, which are accompanied by deficient nutrient and oxygen supply of muscle fibers.

Cardiac system bioenergetics: metabolic basis of the Frank-Starling law

PubMed Central

Saks, Valdur; Dzeja, Petras; Schlattner, Uwe; Vendelin, Marko; Terzic, Andre; Wallimann, Theo

2006-01-01

The fundamental principle of cardiac behaviour is described by the Frank-Starling law relating force of contraction during systole with end-diastolic volume. While both work and respiration rates increase linearly with imposed load, the basis of mechano-energetic coupling in heart muscle has remained a long-standing enigma. Here, we highlight advances made in understanding of complex cellular and molecular mechanisms that orchestrate coupling of mitochondrial oxidative phosphorylation with ATP utilization for muscle contraction. Cardiac system bioenergetics critically depends on an interrelated metabolic infrastructure regulating mitochondrial respiration and energy fluxes throughout cellular compartments. The data reviewed indicate the significance of two interrelated systems regulating mitochondrial respiration and energy fluxes in cells: (1) the creatine kinase, adenylate kinase and glycolytic pathways that communicate flux changes generated by cellular ATPases within structurally organized enzymatic modules and networks; and (2) a secondary system based on mitochondrial participation in cellular calcium cycle, which adjusts substrate oxidation and energy-transducing processes to meet increasing cellular energy demands. By conveying energetic signals to metabolic sensors, coupled phosphotransfer reactions provide a high-fidelity regulation of the excitation–contraction cycle. Such integration of energetics with calcium signalling systems provides the basis for ‘metabolic pacing’, synchronizing the cellular electrical and mechanical activities with energy supply processes. PMID:16410283

Insights into the key roles of epigenetics in matrix macromolecules-associated wound healing.

PubMed

Piperigkou, Zoi; Götte, Martin; Theocharis, Achilleas D; Karamanos, Nikos K

2017-10-24

Extracellular matrix (ECM) is a dynamic network of macromolecules, playing a regulatory role in cell functions, tissue regeneration and remodeling. Wound healing is a tissue repair process necessary for the maintenance of the functionality of tissues and organs. This highly orchestrated process is divided into four temporally overlapping phases, including hemostasis, inflammation, proliferation and tissue remodeling. The dynamic interplay between ECM and resident cells exerts its critical role in many aspects of wound healing, including cell proliferation, migration, differentiation, survival, matrix degradation and biosynthesis. Several epigenetic regulatory factors, such as the endogenous non-coding microRNAs (miRNAs), are the drivers of the wound healing response. microRNAs have pivotal roles in regulating ECM composition during wound healing and dermal regeneration. Their expression is associated with the distinct phases of wound healing and they serve as target biomarkers and targets for systematic regulation of wound repair. In this article we critically present the importance of epigenetics with particular emphasis on miRNAs regulating ECM components (i.e. glycoproteins, proteoglycans and matrix proteases) that are key players in wound healing. The clinical relevance of miRNA targeting as well as the delivery strategies designed for clinical applications are also presented and discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Agile IT: Thinking in User-Centric Models

NASA Astrophysics Data System (ADS)

Margaria, Tiziana; Steffen, Bernhard

We advocate a new teaching direction for modern CS curricula: extreme model-driven development (XMDD), a new development paradigm designed to continuously involve the customer/application expert throughout the whole systems' life cycle. Based on the `One-Thing Approach', which works by successively enriching and refining one single artifact, system development becomes in essence a user-centric orchestration of intuitive service functionality. XMDD differs radically from classical software development, which, in our opinion is no longer adequate for the bulk of application programming - in particular when it comes to heterogeneous, cross organizational systems which must adapt to rapidly changing market requirements. Thus there is a need for new curricula addressing this model-driven, lightweight, and cooperative development paradigm that puts the user process in the center of the development and the application expert in control of the process evolution.

Understanding nitrate uptake, signaling and remobilisation for improving plant nitrogen use efficiency.

PubMed

Kant, Surya

2018-02-01

The majority of terrestrial plants use nitrate as their main source of nitrogen. Nitrate also acts as an important signalling molecule in vital physiological processes required for optimum plant growth and development. Improving nitrate uptake and transport, through activation by nitrate sensing, signalling and regulatory processes, would enhance plant growth, resulting in improved crop yields. The increased remobilisation of nitrate, and assimilated nitrogenous compounds, from source to sink tissues further ensures higher yields and quality. An updated knowledge of various transporters, genes, activators, and microRNAs, involved in nitrate uptake, transport, remobilisation, and nitrate-mediated root growth, is presented. An enhanced understanding of these components will allow for their orchestrated fine tuning in efforts to improving nitrogen use efficiency in plants. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

A defined role for multiple Fanconi anemia gene products in DNA-damage-associated ubiquitination.

PubMed

Tan, Winnie; Deans, Andrew J

2017-06-01

Fanconi anemia (FA) is an inherited blood disorder that causes bone marrow failure and high predisposition to cancers. The FA pathway guards the cell's genome stability by orchestrating the repair of interstrand cross-linking during the S phase of the cell cycle, preventing the chromosomal instability that is a key event in bone marrow failure syndrome. Central to the FA pathway is loss of monoubiquitinated forms of the Fanconi proteins FANCI and FANCD2, a process that is normally mediated by a "core complex" of seven other Fanconi proteins. Each protein, when mutated, can cause FA. The FA core-complex-catalyzed reaction is critical for signaling DNA cross-link damage such as that induced by chemotherapies. Here, we present a perspective on the current understanding of FANCI and FANCD2 monoubiquitination-mediated DNA repair. Our recent biochemical reconstitution of the monoubiquitination (and deubiquitination) reactions creates a paradigm for understanding FA. Further biochemical analysis will create new opportunities to address the leukemic phenotype of FA patients. Copyright © 2017 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

System-Wide Hypersensitive Response-Associated Transcriptome and Metabolome Reprogramming in Tomato1[W][OA

PubMed Central

Etalo, Desalegn W.; Stulemeijer, Iris J.E.; Peter van Esse, H.; de Vos, Ric C.H.; Bouwmeester, Harro J.; Joosten, Matthieu H.A.J.

2013-01-01

The hypersensitive response (HR) is considered to be the hallmark of the resistance response of plants to pathogens. To study HR-associated transcriptome and metabolome reprogramming in tomato (Solanum lycopersicum), we used plants that express both a resistance gene to Cladosporium fulvum and the matching avirulence gene of this pathogen. In these plants, massive reprogramming occurred, and we found that the HR and associated processes are highly energy demanding. Ubiquitin-dependent protein degradation, hydrolysis of sugars, and lipid catabolism are used as alternative sources of amino acids, energy, and carbon skeletons, respectively. We observed strong accumulation of secondary metabolites, such as hydroxycinnamic acid amides. Coregulated expression of WRKY transcription factors and genes known to be involved in the HR, in addition to a strong enrichment of the W-box WRKY-binding motif in the promoter sequences of the coregulated genes, point to WRKYs as the most prominent orchestrators of the HR. Our study has revealed several novel HR-related genes, and reverse genetics tools will allow us to understand the role of each individual component in the HR. PMID:23719893

Characterization of axon formation in the embryonic stem cell-derived motoneuron.

PubMed

Pan, Hung-Chuan; Wu, Ya-Ting; Shen, Shih-Cheng; Wang, Chi-Chung; Tsai, Ming-Shiun; Cheng, Fu-Chou; Lin, Shinn-Zong; Chen, Ching-Wen; Liu, Ching-San; Su, Hong-Lin

2011-01-01

The developing neural cell must form a highly organized architecture to properly receive and transmit nerve signals. Neural formation from embryonic stem (ES) cells provides a novel system for studying axonogenesis, which are orchestrated by polarity-regulating molecules. Here the ES-derived motoneurons, identified by HB9 promoter-driven green fluorescent protein (GFP) expression, showed characteristics of motoneuron-specific gene expression. In the majority of motoneurons, one of the bilateral neurites developed into an axon that featured with axonal markers, including Tau1, vesicle acetylcholine transporter, and synaptophysin. Interestingly, one third of the motoneurons developed bi-axonal processes but no multiple axonal GFP cell was found. The neuronal polarity-regulating proteins, including the phosphorylated AKT and ERK, were compartmentalized into both of the bilateral axonal tips. Importantly, this aberrant axon morphology was still present after the engraftment of GFP(+) neurons into the spinal cord, suggesting that even a mature neural environment fails to provide a proper niche to guide normal axon formation. These findings underscore the necessity for evaluating the morphogenesis and functionality of neurons before the clinical trials using ES or somatic stem cells.

Biofabrication strategies for 3D in vitro models and regenerative medicine

NASA Astrophysics Data System (ADS)

Moroni, Lorenzo; Burdick, Jason A.; Highley, Christopher; Lee, Sang Jin; Morimoto, Yuya; Takeuchi, Shoji; Yoo, James J.

2018-05-01

Organs are complex systems composed of different cells, proteins and signalling molecules that are arranged in a highly ordered structure to orchestrate a myriad of functions in our body. Biofabrication strategies can be applied to engineer 3D tissue models in vitro by mimicking the structure and function of native tissue through the precise deposition and assembly of materials and cells. This approach allows the spatiotemporal control over cell-cell and cell-extracellular matrix communication and thus the recreation of tissue-like structures. In this Review, we examine biofabrication strategies for the construction of functional tissue replacements and organ models, focusing on the development of biomaterials, such as supramolecular and photosensitive materials, that can be processed using biofabrication techniques. We highlight bioprinted and bioassembled tissue models and survey biofabrication techniques for their potential to recreate complex tissue properties, such as shape, vasculature and specific functionalities. Finally, we discuss challenges, such as scalability and the foreign body response, and opportunities in the field and provide an outlook to the future of biofabrication in regenerative medicine.

Habituation as an adaptive shift in response strategy mediated by neuropeptides

NASA Astrophysics Data System (ADS)

Ardiel, Evan L.; Yu, Alex J.; Giles, Andrew C.; Rankin, Catharine H.

2017-08-01

Habituation is a non-associative form of learning characterized by a decremented response to repeated stimulation. It is typically framed as a process of selective attention, allowing animals to ignore irrelevant stimuli in order to free up limited cognitive resources. However, habituation can also occur to threatening and toxic stimuli, suggesting that habituation may serve other functions. Here we took advantage of a high-throughput Caenorhabditis elegans learning assay to investigate habituation to noxious stimuli. Using real-time computer vision software for automated behavioral tracking and optogenetics for controlled activation of a polymodal nociceptor, ASH, we found that neuropeptides mediated habituation and performed an RNAi screen to identify candidate receptors. Through subsequent mutant analysis and cell-type-specific gene expression, we found that pigment-dispersing factor (PDF) neuropeptides function redundantly to promote habituation via PDFR-1-mediated cAMP signaling in both neurons and muscles. Behavioral analysis during learning acquisition suggests that response habituation and sensitization of locomotion are parts of a shifting behavioral strategy orchestrated by pigment dispersing factor signaling to promote dispersal away from repeated aversive stimuli.

Slow oscillations orchestrating fast oscillations and memory consolidation.

PubMed

Mölle, Matthias; Born, Jan

2011-01-01

Slow-wave sleep (SWS) facilitates the consolidation of hippocampus-dependent declarative memory. Based on the standard two-stage memory model, we propose that memory consolidation during SWS represents a process of system consolidation which is orchestrated by the neocortical <1Hz electroencephalogram (EEG) slow oscillation and involves the reactivation of newly encoded representations and their subsequent redistribution from temporary hippocampal to neocortical long-term storage sites. Indeed, experimental induction of slow oscillations during non-rapid eye movement (non-REM) sleep by slowly alternating transcranial current stimulation distinctly improves consolidation of declarative memory. The slow oscillations temporally group neuronal activity into up-states of strongly enhanced neuronal activity and down-states of neuronal silence. In a feed-forward efferent action, this grouping is induced not only in the neocortex but also in other structures relevant to consolidation, namely the thalamus generating 10-15Hz spindles, and the hippocampus generating sharp wave-ripples, with the latter well known to accompany a replay of newly encoded memories taking place in hippocampal circuitries. The feed-forward synchronizing effect of the slow oscillation enables the formation of spindle-ripple events where ripples and accompanying reactivated hippocampal memory information become nested into the single troughs of spindles. Spindle-ripple events thus enable reactivated memory-related hippocampal information to be fed back to neocortical networks in the excitable slow oscillation up-state where they can induce enduring plastic synaptic changes underlying the effective formation of long-term memories. Copyright © 2011 Elsevier B.V. All rights reserved.

The COGs (context, object, and goals) in multisensory processing.

PubMed

ten Oever, Sanne; Romei, Vincenzo; van Atteveldt, Nienke; Soto-Faraco, Salvador; Murray, Micah M; Matusz, Pawel J

2016-05-01

Our understanding of how perception operates in real-world environments has been substantially advanced by studying both multisensory processes and "top-down" control processes influencing sensory processing via activity from higher-order brain areas, such as attention, memory, and expectations. As the two topics have been traditionally studied separately, the mechanisms orchestrating real-world multisensory processing remain unclear. Past work has revealed that the observer's goals gate the influence of many multisensory processes on brain and behavioural responses, whereas some other multisensory processes might occur independently of these goals. Consequently, other forms of top-down control beyond goal dependence are necessary to explain the full range of multisensory effects currently reported at the brain and the cognitive level. These forms of control include sensitivity to stimulus context as well as the detection of matches (or lack thereof) between a multisensory stimulus and categorical attributes of naturalistic objects (e.g. tools, animals). In this review we discuss and integrate the existing findings that demonstrate the importance of such goal-, object- and context-based top-down control over multisensory processing. We then put forward a few principles emerging from this literature review with respect to the mechanisms underlying multisensory processing and discuss their possible broader implications.

Workflow-Based Software Development Environment

NASA Technical Reports Server (NTRS)

Izygon, Michel E.

2013-01-01

The Software Developer's Assistant (SDA) helps software teams more efficiently and accurately conduct or execute software processes associated with NASA mission-critical software. SDA is a process enactment platform that guides software teams through project-specific standards, processes, and procedures. Software projects are decomposed into all of their required process steps or tasks, and each task is assigned to project personnel. SDA orchestrates the performance of work required to complete all process tasks in the correct sequence. The software then notifies team members when they may begin work on their assigned tasks and provides the tools, instructions, reference materials, and supportive artifacts that allow users to compliantly perform the work. A combination of technology components captures and enacts any software process use to support the software lifecycle. It creates an adaptive workflow environment that can be modified as needed. SDA achieves software process automation through a Business Process Management (BPM) approach to managing the software lifecycle for mission-critical projects. It contains five main parts: TieFlow (workflow engine), Business Rules (rules to alter process flow), Common Repository (storage for project artifacts, versions, history, schedules, etc.), SOA (interface to allow internal, GFE, or COTS tools integration), and the Web Portal Interface (collaborative web environment

Underutilization of worker's compensation insurance among professional orchestral musicians.

PubMed

Chimenti, Ruth L; Van Dillen, Linda R; Prather, Heidi; Hunt, Devyani; Chimenti, Peter C; Khoo-Summers, Lynnette

2013-03-01

Orchestral musicians commonly have playing-related symptoms (PRS) but few use worker's compensation (WC) insurance for assessment and treatment. The purpose of this study was to examine the frequency of, and factors related to, filing a WC claim among musicians. An online questionnaire was completed by 261 members of the International Conference of Symphony and Opera Musicians (ICSOM). The responses were analyzed to describe the frequency and type of injuries, perceived cause of PRS, and severity of injury in musicians who did and did not file a WC claim. Of the musicians, 93% reported PRS in the 12 months prior to the study. Only 9 musicians filed WC claims during their careers, and all claims were for upper extremity injuries. The most frequent reason for not filing a WC claim was insufficient severity. Yet among musicians describing their PRS as not severe enough for a WC claim, 47% had symptoms for >15 minutes after playing and 16% had symptoms that interfered with daily activities. These data suggest there is frequent under-reporting of injuries to WC among professional orchestral musicians. Although most musicians reported PRS that persisted after playing, the most common reason for not filing a WC claim was insufficient severity of symptoms perceived by the musicians. Future research should focus on clearly defining severity for PRS-related injuries and determining when treatment for overuse syndromes should be paid for through the WC system.

Demonstration of application-driven network slicing and orchestration in optical/packet domains: on-demand vDC expansion for Hadoop MapReduce optimization.

PubMed

Kong, Bingxin; Liu, Siqi; Yin, Jie; Li, Shengru; Zhu, Zuqing

2018-05-28

Nowadays, it is common for service providers (SPs) to leverage hybrid clouds to improve the quality-of-service (QoS) of their Big Data applications. However, for achieving guaranteed latency and/or bandwidth in its hybrid cloud, an SP might desire to have a virtual datacenter (vDC) network, in which it can manage and manipulate the network connections freely. To address this requirement, we design and implement a network slicing and orchestration (NSO) system that can create and expand vDCs across optical/packet domains on-demand. Considering Hadoop MapReduce (M/R) as the use-case, we describe the proposed architectures of the system's data, control and management planes, and present the operation procedures for creating, expanding, monitoring and managing a vDC for M/R optimization. The proposed NSO system is then realized in a small-scale network testbed that includes four optical/packet domains, and we conduct experiments in it to demonstrate the whole operations of the data, control and management planes. Our experimental results verify that application-driven on-demand vDC expansion across optical/packet domains can be achieved for M/R optimization, and after being provisioned with a vDC, the SP using the NSO system can fully control the vDC network and further optimize the M/R jobs in it with network orchestration.

NEAT1 Scaffolds RNA Binding Proteins and the Microprocessor to Globally Enhance Pri-miRNA Processing

PubMed Central

Jiang, Li; Shao, Changwei; Wu, Qi-Jia; Chen, Geng; Zhou, Jie; Yang, Bo; Li, Hairi; Gou, Lan-Tao; Zhang, Yi; Wang, Yangming; Yeo, Gene W.; Zhou, Yu; Fu, Xiang-Dong

2018-01-01

Summary MicroRNA biogenesis is known to be modulated by a variety of RNA binding proteins (RBPs), but in most cases, individual RBPs appear to influence the processing of a small subset of target miRNAs. We herein report that the RNA binding NONO/PSF heterodimer binds a large number of expressed pri-miRNAs in HeLa cells to globally enhance pri-miRNA processing by the Drosha/DGCR8 Microprocessor. Because NONO/PSF are key components of paraspeckles organized by the lncRNA NEAT1, we further demonstrate that NEAT1 also has a profound effect on global pri-miRNA processing. Mechanistic dissection reveals that NEAT1 broadly interacts with NONO/PSF as well as many other RBPs, and that multiple RNA segments in NEAT1, including a “pseudo pri-miRNA” near its 3′ end, help attract the Microprocessor. These findings suggest a bird nest model for a large non-coding RNA to orchestrate efficient processing of almost an entire class of small non-coding RNAs in the nucleus. PMID:28846091

NEAT1 scaffolds RNA-binding proteins and the Microprocessor to globally enhance pri-miRNA processing.

PubMed

Jiang, Li; Shao, Changwei; Wu, Qi-Jia; Chen, Geng; Zhou, Jie; Yang, Bo; Li, Hairi; Gou, Lan-Tao; Zhang, Yi; Wang, Yangming; Yeo, Gene W; Zhou, Yu; Fu, Xiang-Dong

2017-10-01

MicroRNA (miRNA) biogenesis is known to be modulated by a variety of RNA-binding proteins (RBPs), but in most cases, individual RBPs appear to influence the processing of a small subset of target miRNAs. Here, we report that the RNA-binding NONO-PSF heterodimer binds a large number of expressed pri-miRNAs in HeLa cells to globally enhance pri-miRNA processing by the Drosha-DGCR8 Microprocessor. NONO and PSF are key components of paraspeckles organized by the long noncoding RNA (lncRNA) NEAT1. We further demonstrate that NEAT1 also has a profound effect on global pri-miRNA processing. Mechanistic dissection reveals that NEAT1 broadly interacts with the NONO-PSF heterodimer as well as many other RBPs and that multiple RNA segments in NEAT1, including a 'pseudo pri-miRNA' near its 3' end, help attract the Microprocessor. These findings suggest a 'bird nest' model in which an lncRNA orchestrates efficient processing of potentially an entire class of small noncoding RNAs in the nucleus.

A BPMN solution for chaining OGC services to quality assure location-based crowdsourced data

NASA Astrophysics Data System (ADS)

Meek, Sam; Jackson, Mike; Leibovici, Didier G.

2016-02-01

The Open Geospatial Consortium (OGC) Web Processing Service (WPS) standard enables access to a centralized repository of processes and services from compliant clients. A crucial part of the standard includes the provision to chain disparate processes and services to form a reusable workflow. To date this has been realized by methods such as embedding XML requests, using Business Process Execution Language (BPEL) engines and other external orchestration engines. Although these allow the user to define tasks and data artifacts as web services, they are often considered inflexible and complicated, often due to vendor specific solutions and inaccessible documentation. This paper introduces a new method of flexible service chaining using the standard Business Process Markup Notation (BPMN). A prototype system has been developed upon an existing open source BPMN suite to illustrate the advantages of the approach. The motivation for the software design is qualification of crowdsourced data for use in policy-making. The software is tested as part of a project that seeks to qualify, assure, and add value to crowdsourced data in a biological monitoring use case.

Creative thinking as orchestrated by semantic processing vs. cognitive control brain networks

PubMed Central

Abraham, Anna

2014-01-01

Creativity is primarily investigated within the neuroscientific perspective as a unitary construct. While such an approach is beneficial when trying to infer the general picture regarding creativity and brain function, it is insufficient if the objective is to uncover the information processing brain mechanisms by which creativity occurs. As creative thinking emerges through the dynamic interplay between several cognitive processes, assessing the neural correlates of these operations would enable the development and characterization of an information processing framework from which to better understand this complex ability. This article focuses on two aspects of creative cognition that are central to generating original ideas. “Conceptual expansion” refers to the ability to widen one’s conceptual structures to include unusual or novel associations, while “overcoming knowledge constraints” refers to our ability to override the constraining influence imposed by salient or pertinent knowledge when trying to be creative. Neuroimaging and neuropsychological evidence is presented to illustrate how semantic processing and cognitive control networks in the brain differentially modulate these critical facets of creative cognition. PMID:24605098

NASA SensorWeb and OGC Standards for Disaster Management

NASA Technical Reports Server (NTRS)

Mandl, Dan

2010-01-01

I. Goal: Enable user to cost-effectively find and create customized data products to help manage disasters; a) On-demand; b) Low cost and non-specialized tools such as Google Earth and browsers; c) Access via open network but with sufficient security. II. Use standards to interface various sensors and resultant data: a) Wrap sensors in Open Geospatial Consortium (OGC) standards; b) Wrap data processing algorithms and servers with OGC standards c) Use standardized workflows to orchestrate and script the creation of these data; products. III. Target Web 2.0 mass market: a) Make it simple and easy to use; b) Leverage new capabilities and tools that are emerging; c) Improve speed and responsiveness.

Three’s company: The fission yeast actin cytoskeleton

PubMed Central

Kovar, David R.; Sirotkin, Vladimir; Lord, Matthew

2010-01-01

How the actin cytoskeleton assembles into different structures to drive diverse cellular processes is a fundamental cell biological question. In addition to orchestrating the appropriate combination of regulators and actin-binding proteins, different actin-based structures must insulate themselves from one another to maintain specificity within a crowded cytoplasm. Actin specification is particularly vexing in complex eukaryotes where a multitude of protein isoforms and actin structures operate within the same cell. Fission yeast Schizosaccharomyces pombe possesses a single actin isoform that functions in three distinct structures throughout the cell cycle. In this review, we explore recent studies in fission yeast that help unravel how different actin structures operate in cells. PMID:21145239

The Hippo pathway: key interaction and catalytic domains in organ growth control, stem cell self-renewal and tissue regeneration.

PubMed

Cherrett, Claire; Furutani-Seiki, Makoto; Bagby, Stefan

2012-01-01

The Hippo pathway is a conserved pathway that interconnects with several other pathways to regulate organ growth, tissue homoeostasis and regeneration, and stem cell self-renewal. This pathway is unique in its capacity to orchestrate multiple processes, from sensing to execution, necessary for organ expansion. Activation of the Hippo pathway core kinase cassette leads to cytoplasmic sequestration of the nuclear effectors YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif), consequently disabling their transcriptional co-activation function. Components upstream of the core kinase cassette have not been well understood, especially in vertebrates, but are gradually being elucidated and include cell polarity and cell adhesion proteins.

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.

Emerging functions of alternative splicing coupled with nonsense-mediated decay.

PubMed

Hamid, Fursham M; Makeyev, Eugene V

2014-08-01

Higher eukaryotes rely on AS (alternative splicing) of pre-mRNAs (mRNA precursors) to generate more than one protein product from a single gene and to regulate mRNA stability and translational activity. An important example of the latter function involves an interplay between AS and NMD (nonsense-mediated decay), a cytoplasmic quality control mechanism eliminating mRNAs containing PTCs (premature translation termination codons). Although originally identified as an error surveillance process, AS-NMD additionally provides an efficient strategy for deterministic regulation of gene expression outputs. In this review, we discuss recently published examples of AS-NMD and delineate functional contexts where recurrent use of this mechanism orchestrates expression of important genes.

Forging Ahead through Darkness: PCNA, Still the Principal Conductor at the Replication Fork.

PubMed

Choe, Katherine N; Moldovan, George-Lucian

2017-02-02

Proliferating cell nuclear antigen (PCNA) lies at the center of the faithful duplication of eukaryotic genomes. With its distinctive doughnut-shaped molecular structure, PCNA was originally studied for its role in stimulating DNA polymerases. However, we now know that PCNA does much more than promote processive DNA synthesis. Because of the complexity of the events involved, cellular DNA replication poses major threats to genomic integrity. Whatever predicament lies ahead for the replication fork, PCNA is there to orchestrate the events necessary to handle it. Through its many protein interactions and various post-translational modifications, PCNA has far-reaching impacts on a myriad of cellular functions. Copyright © 2017 Elsevier Inc. All rights reserved.

MYC and metabolism on the path to cancer

PubMed Central

Hsieh, Annie L.; Walton, Zandra E.; Altman, Brian J.; Stine, Zachary E.; Dang, Chi V.

2015-01-01

The MYC proto-oncogene is frequently deregulated in human cancers, activating genetic programs that orchestrate biological processes to promote growth and proliferation. Altered metabolism characterized by heightened nutrients uptake, enhanced glycolysis and glutaminolysis and elevated fatty acid and nucleotide synthesis is the hallmark of MYC-driven cancer. Recent evidence strongly suggests that Myc-dependent metabolic reprogramming is critical for tumorigenesis, which could be attenuated by targeting specific metabolic pathways using small drug-like molecules. Understanding the complexity of MYC-mediated metabolic re-wiring in cancers as well as how MYC cooperates with other metabolic drivers such as mammalian target of rapamycin (mTOR) will provide translational opportunities for cancer therapy. PMID:26277543

Elucidation of Sigma Factor-Associated Networks in Pseudomonas aeruginosa Reveals a Modular Architecture with Limited and Function-Specific Crosstalk

PubMed Central

Schulz, Sebastian; Eckweiler, Denitsa; Bielecka, Agata; Nicolai, Tanja; Franke, Raimo; Dötsch, Andreas; Hornischer, Klaus; Bruchmann, Sebastian; Düvel, Juliane; Häussler, Susanne

2015-01-01

Sigma factors are essential global regulators of transcription initiation in bacteria which confer promoter recognition specificity to the RNA polymerase core enzyme. They provide effective mechanisms for simultaneously regulating expression of large numbers of genes in response to challenging conditions, and their presence has been linked to bacterial virulence and pathogenicity. In this study, we constructed nine his-tagged sigma factor expressing and/or deletion mutant strains in the opportunistic pathogen Pseudomonas aeruginosa. To uncover the direct and indirect sigma factor regulons, we performed mRNA profiling, as well as chromatin immunoprecipitation coupled to high-throughput sequencing. We furthermore elucidated the de novo binding motif of each sigma factor, and validated the RNA- and ChIP-seq results by global motif searches in the proximity of transcriptional start sites (TSS). Our integrated approach revealed a highly modular network architecture which is composed of insulated functional sigma factor modules. Analysis of the interconnectivity of the various sigma factor networks uncovered a limited, but highly function-specific, crosstalk which orchestrates complex cellular processes. Our data indicate that the modular structure of sigma factor networks enables P. aeruginosa to function adequately in its environment and at the same time is exploited to build up higher-level functions by specific interconnections that are dominated by a participation of RpoN. PMID:25780925

Cloud-Based Orchestration of a Model-Based Power and Data Analysis Toolchain

NASA Technical Reports Server (NTRS)

Post, Ethan; Cole, Bjorn; Dinkel, Kevin; Kim, Hongman; Lee, Erich; Nairouz, Bassem

2016-01-01

The proposed Europa Mission concept contains many engineering and scientific instruments that consume varying amounts of power and produce varying amounts of data throughout the mission. System-level power and data usage must be well understood and analyzed to verify design requirements. Numerous cross-disciplinary tools and analysis models are used to simulate the system-level spacecraft power and data behavior. This paper addresses the problem of orchestrating a consistent set of models, tools, and data in a unified analysis toolchain when ownership is distributed among numerous domain experts. An analysis and simulation environment was developed as a way to manage the complexity of the power and data analysis toolchain and to reduce the simulation turnaround time. A system model data repository is used as the trusted store of high-level inputs and results while other remote servers are used for archival of larger data sets and for analysis tool execution. Simulation data passes through numerous domain-specific analysis tools and end-to-end simulation execution is enabled through a web-based tool. The use of a cloud-based service facilitates coordination among distributed developers and enables scalable computation and storage needs, and ensures a consistent execution environment. Configuration management is emphasized to maintain traceability between current and historical simulation runs and their corresponding versions of models, tools and data.

Age-Related Differences in Working Memory Performance in A 2-Back Task

PubMed Central

Wild-Wall, Nele; Falkenstein, Michael; Gajewski, Patrick D.

2011-01-01

The present study aimed to elucidate the neuro-cognitive processes underlying age-related differences in working memory. Young and middle-aged participants performed a two-choice task with low and a 2-back task with high working memory load. The P300, an event-related potential reflecting controlled stimulus–response processing in working memory, and the underlying neuronal sources of expected age-related differences were analyzed using sLORETA. Response speed was generally slower for the middle-aged than the young group. Under low working memory load the middle-aged participants traded speed for accuracy. The middle-aged were less efficient in the 2-back task as they responded slower while the error rates did not differ for groups. An age-related decline of the P300 amplitude and characteristic topographical differences were especially evident in the 2-back task. A more detailed analysis of the P300 in non-target trials revealed that amplitudes in the young but not middle-aged group differentiate between correctly detected vs. missed targets in the following trial. For these trials, source analysis revealed higher activation for the young vs. middle-aged group in brain areas which support working memory processes. The relationship between P300 and overt performance was validated by significant correlations. To sum up, under high working memory load the young group showed an increased neuronal activity before a successful detected target, while the middle-aged group showed the same neuronal pattern regardless of whether a subsequent target will be detected or missed. This stable memory trace before detected targets was reflected by a specific activation enhancement in brain areas which orchestrate maintenance, update, storage, and retrieval of information in working memory. PMID:21909328

The dynamics and tuning of orchestral crotales

NASA Astrophysics Data System (ADS)

Deutsch, Bradley M.; Ramirez, Cherie L.; Moore, Thomas R.

2004-10-01

An experimental and theoretical investigation of the acoustic and vibrational properties of orchestral crotales within the range C6 to C8 is reported. Interferograms of the acoustically important modes of vibration are presented and the frequencies are reported. It is shown that the acoustic spectra of crotales are not predicted by assuming that they are either thin circular plates or annular plates clamped at the center, despite the physical resemblance to these objects. Results from finite element analysis are presented that demonstrate how changing the size of the central mass affects the tuning of the instruments, and it is concluded that crotales are not currently designed to ensure optimal tuning. The possibility of using annular plates as crotales is also investigated and the physical parameters for such a set of instruments are presented. .

Adolescent Development of Value-Guided Goal Pursuit.

PubMed

Davidow, Juliet Y; Insel, Catherine; Somerville, Leah H

2018-06-04

Adolescents are challenged to orchestrate goal-directed actions in increasingly independent and consequential ways. In doing so, it is advantageous to use information about value to select which goals to pursue and how much effort to devote to them. Here, we examine age-related changes in how individuals use value signals to orchestrate goal-directed behavior. Drawing on emerging literature on value-guided cognitive control and reinforcement learning, we demonstrate how value and task difficulty modulate the execution of goal-directed action in complex ways across development from childhood to adulthood. We propose that the scope of value-guided goal pursuit expands with age to include increasingly challenging cognitive demands, and scaffolds on the emergence of functional integration within brain networks supporting valuation, cognition, and action. Copyright © 2018 Elsevier Ltd. All rights reserved.

ROS-induced ROS release orchestrated by Nox4, Nox2, and mitochondria in VEGF signaling and angiogenesis.

PubMed

Kim, Young-Mee; Kim, Seok-Jo; Tatsunami, Ryosuke; Yamamura, Hisao; Fukai, Tohru; Ushio-Fukai, Masuko

2017-06-01

Reactive oxygen species (ROS) derived from NADPH oxidase (NOX) and mitochondria play a critical role in growth factor-induced switch from a quiescent to an angiogenic phenotype in endothelial cells (ECs). However, how highly diffusible ROS produced from different sources can coordinate to stimulate VEGF signaling and drive the angiogenic process remains unknown. Using the cytosol- and mitochondria-targeted redox-sensitive RoGFP biosensors with real-time imaging, here we show that VEGF stimulation in human ECs rapidly increases cytosolic RoGFP oxidation within 1 min, followed by mitochondrial RoGFP oxidation within 5 min, which continues at least for 60 min. Silencing of Nox4 or Nox2 or overexpression of mitochondria-targeted catalase significantly inhibits VEGF-induced tyrosine phosphorylation of VEGF receptor type 2 (VEGFR2-pY), EC migration and proliferation at the similar extent. Exogenous hydrogen peroxide (H 2 O 2 ) or overexpression of Nox4, which produces H 2 O 2 , increases mitochondrial ROS (mtROS), which is prevented by Nox2 siRNA, suggesting that Nox2 senses Nox4-derived H 2 O 2 to promote mtROS production. Mechanistically, H 2 O 2 increases S36 phosphorylation of p66Shc, a key mtROS regulator, which is inhibited by siNox2, but not by siNox4. Moreover, Nox2 or Nox4 knockdown or overexpression of S36 phosphorylation-defective mutant p66Shc(S36A) inhibits VEGF-induced mtROS, VEGFR2-pY, EC migration, and proliferation. In summary, Nox4-derived H 2 O 2 in part activates Nox2 to increase mtROS via pSer36-p66Shc, thereby enhancing VEGFR2 signaling and angiogenesis in ECs. This may represent a novel feed-forward mechanism of ROS-induced ROS release orchestrated by the Nox4/Nox2/pSer36-p66Shc/mtROS axis, which drives sustained activation of angiogenesis signaling program. Copyright © 2017 the American Physiological Society.

Membrane dynamics associated with viral infection.

PubMed

de Armas-Rillo, Laura; Valera, María-Soledad; Marrero-Hernández, Sara; Valenzuela-Fernández, Agustín

2016-05-01

Viral replication and spreading are fundamental events in the viral life cycle, accounting for the assembly and egression of nascent virions, events that are directly associated with viral pathogenesis in target hosts. These processes occur in cellular compartments that are modified by specialized viral proteins, causing a rearrangement of different cell membranes in infected cells and affecting the ER, mitochondria, Golgi apparatus, vesicles and endosomes, as well as processes such as autophagic membrane flux. In fact, the activation or inhibition of membrane trafficking and other related activities are fundamental to ensure the adequate replication and spreading of certain viruses. In this review, data will be presented that support the key role of membrane dynamics in the viral cycle, especially in terms of the assembly, egression and infection processes. By defining how viruses orchestrate these events it will be possible to understand how they successfully complete their route of infection, establishing viral pathogenesis and provoking disease. © 2015 The Authors Reviews in Medical Virology Published by John Wiley & Sons, Ltd.

Weighted Ensemble Simulation: Review of Methodology, Applications, and Software

PubMed Central

Zuckerman, Daniel M.; Chong, Lillian T.

2018-01-01

The weighted ensemble (WE) methodology orchestrates quasi-independent parallel simulations run with intermittent communication that can enhance sampling of rare events such as protein conformational changes, folding, and binding. The WE strategy can achieve superlinear scaling—the unbiased estimation of key observables such as rate constants and equilibrium state populations to greater precision than would be possible with ordinary parallel simulation. WE software can be used to control any dynamics engine, such as standard molecular dynamics and cell-modeling packages. This article reviews the theoretical basis of WE and goes on to describe successful applications to a number of complex biological processes—protein conformational transitions, (un)binding, and assembly processes, as well as cell-scale processes in systems biology. We furthermore discuss the challenges that need to be overcome in the next phase of WE methodological development. Overall, the combined advances in WE methodology and software have enabled the simulation of long-timescale processes that would otherwise not be practical on typical computing resources using standard simulation. PMID:28301772

RNA search engines empower the bacterial intranet.

PubMed

Dendooven, Tom; Luisi, Ben F

2017-08-15

RNA acts not only as an information bearer in the biogenesis of proteins from genes, but also as a regulator that participates in the control of gene expression. In bacteria, small RNA molecules (sRNAs) play controlling roles in numerous processes and help to orchestrate complex regulatory networks. Such processes include cell growth and development, response to stress and metabolic change, transcription termination, cell-to-cell communication, and the launching of programmes for host invasion. All these processes require recognition of target messenger RNAs by the sRNAs. This review summarizes recent results that have provided insights into how bacterial sRNAs are recruited into effector ribonucleoprotein complexes that can seek out and act upon target transcripts. The results hint at how sRNAs and their protein partners act as pattern-matching search engines that efficaciously regulate gene expression, by performing with specificity and speed while avoiding off-target effects. The requirements for efficient searches of RNA patterns appear to be common to all domains of life. © 2017 The Author(s).

RNA search engines empower the bacterial intranet

PubMed Central

Dendooven, Tom

2017-01-01

RNA acts not only as an information bearer in the biogenesis of proteins from genes, but also as a regulator that participates in the control of gene expression. In bacteria, small RNA molecules (sRNAs) play controlling roles in numerous processes and help to orchestrate complex regulatory networks. Such processes include cell growth and development, response to stress and metabolic change, transcription termination, cell-to-cell communication, and the launching of programmes for host invasion. All these processes require recognition of target messenger RNAs by the sRNAs. This review summarizes recent results that have provided insights into how bacterial sRNAs are recruited into effector ribonucleoprotein complexes that can seek out and act upon target transcripts. The results hint at how sRNAs and their protein partners act as pattern-matching search engines that efficaciously regulate gene expression, by performing with specificity and speed while avoiding off-target effects. The requirements for efficient searches of RNA patterns appear to be common to all domains of life. PMID:28710287

A Symphony of Software.

ERIC Educational Resources Information Center

Currents, 2002

2002-01-01

Offers a descriptive table of databases that help higher education institutions orchestrate advancement operations. Information includes vendor, contact, software, price, database engine/server platform, recommended reporting tools, record capacity, and client type. (EV)

Automated Formosat Image Processing System for Rapid Response to International Disasters

NASA Astrophysics Data System (ADS)

Cheng, M. C.; Chou, S. C.; Chen, Y. C.; Chen, B.; Liu, C.; Yu, S. J.

2016-06-01

FORMOSAT-2, Taiwan's first remote sensing satellite, was successfully launched in May of 2004 into the Sun-synchronous orbit at 891 kilometers of altitude. With the daily revisit feature, the 2-m panchromatic, 8-m multi-spectral resolution images captured have been used for researches and operations in various societal benefit areas. This paper details the orchestration of various tasks conducted in different institutions in Taiwan in the efforts responding to international disasters. The institutes involved including its space agency-National Space Organization (NSPO), Center for Satellite Remote Sensing Research of National Central University, GIS Center of Feng-Chia University, and the National Center for High-performance Computing. Since each institution has its own mandate, the coordinated tasks ranged from receiving emergency observation requests, scheduling and tasking of satellite operation, downlink to ground stations, images processing including data injection, ortho-rectification, to delivery of image products. With the lessons learned from working with international partners, the FORMOSAT Image Processing System has been extensively automated and streamlined with a goal to shorten the time between request and delivery in an efficient manner. The integrated team has developed an Application Interface to its system platform that provides functions of search in archive catalogue, request of data services, mission planning, inquiry of services status, and image download. This automated system enables timely image acquisition and substantially increases the value of data product. Example outcome of these efforts in recent response to support Sentinel Asia in Nepal Earthquake is demonstrated herein.

Pleural innate response activator B cells protect against pneumonia via a GM-CSF-IgM axis

PubMed Central

Chousterman, Benjamin G.; Hilgendorf, Ingo; Robbins, Clinton S.; Theurl, Igor; Gerhardt, Louisa M.S.; Iwamoto, Yoshiko; Quach, Tam D.; Ali, Muhammad; Chen, John W.; Rothstein, Thomas L.; Nahrendorf, Matthias; Weissleder, Ralph

2014-01-01

Pneumonia is a major cause of mortality worldwide and a serious problem in critical care medicine, but the immunophysiological processes that confer either protection or morbidity are not completely understood. We show that in response to lung infection, B1a B cells migrate from the pleural space to the lung parenchyma to secrete polyreactive emergency immunoglobulin M (IgM). The process requires innate response activator (IRA) B cells, a transitional B1a-derived inflammatory subset which controls IgM production via autocrine granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. The strategic location of these cells, coupled with the capacity to produce GM-CSF–dependent IgM, ensures effective early frontline defense against bacteria invading the lungs. The study describes a previously unrecognized GM-CSF-IgM axis and positions IRA B cells as orchestrators of protective IgM immunity. PMID:24821911

Regulators of spindle microtubules and their mechanisms: Living together matters.

PubMed

Lakshmi, R Bhagya; Nair, Vishnu M; Manna, Tapas K

2018-02-01

Development and survival of all eukaryotic organisms depend on equal partitioning of their chromosomes between the two newly formed daughter cells during mitosis. The mitotic spindle performs the task of physically segregating the chromosomes through multiple stages of mitosis. During this process, kinetochore-microtubule attachment requires to be selectively stabilized to hold the chromosomes, but at the same time, it has to be flexible enough to allow kinetochore microtubule dynamicity and chromosome movements. Research during the last decade or so has identified a number of proteins associated with the spindle microtubule plus ends that regulate these processes and orchestrate forces to spatially organize and separate the chromosomes. In this review, we describe the molecular details of those regulators and their mechanisms of action at the kinetochore-microtubule interface. © 2018 IUBMB Life, 70(2):101-111, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

Media Ion Composition Controls Regulatory and Virulence Response of Salmonella in Spaceflight

PubMed Central

Wilson, James W.; Ott, C. Mark; Quick, Laura; Davis, Richard; zu Bentrup, Kerstin Höner; Crabbé, Aurélie; Richter, Emily; Sarker, Shameema; Barrila, Jennifer; Porwollik, Steffen; Cheng, Pui; McClelland, Michael; Tsaprailis, George; Radabaugh, Timothy; Hunt, Andrea; Shah, Miti; Nelman-Gonzalez, Mayra; Hing, Steve; Parra, Macarena; Dumars, Paula; Norwood, Kelly; Bober, Ramona; Devich, Jennifer; Ruggles, Ashleigh; CdeBaca, Autumn; Narayan, Satro; Benjamin, Joseph; Goulart, Carla; Rupert, Mark; Catella, Luke; Schurr, Michael J.; Buchanan, Kent; Morici, Lisa; McCracken, James; Porter, Marc D.; Pierson, Duane L.; Smith, Scott M.; Mergeay, Max; Leys, Natalie; Stefanyshyn-Piper, Heidemarie M.; Gorie, Dominic; Nickerson, Cheryl A.

2008-01-01

The spaceflight environment is relevant to conditions encountered by pathogens during the course of infection and induces novel changes in microbial pathogenesis not observed using conventional methods. It is unclear how microbial cells sense spaceflight-associated changes to their growth environment and orchestrate corresponding changes in molecular and physiological phenotypes relevant to the infection process. Here we report that spaceflight-induced increases in Salmonella virulence are regulated by media ion composition, and that phosphate ion is sufficient to alter related pathogenesis responses in a spaceflight analogue model. Using whole genome microarray and proteomic analyses from two independent Space Shuttle missions, we identified evolutionarily conserved molecular pathways in Salmonella that respond to spaceflight under all media compositions tested. Identification of conserved regulatory paradigms opens new avenues to control microbial responses during the infection process and holds promise to provide an improved understanding of human health and disease on Earth. PMID:19079590

Paramyxovirus Glycoproteins and the Membrane Fusion Process.

PubMed

Aguilar, Hector C; Henderson, Bryce A; Zamora, J Lizbeth; Johnston, Gunner P

2016-09-01

The family Paramyxoviridae includes many viruses that significantly affect human and animal health. An essential step in the paramyxovirus life cycle is viral entry into host cells, mediated by virus-cell membrane fusion. Upon viral entry, infection results in expression of the paramyxoviral glycoproteins on the infected cell surface. This can lead to cell-cell fusion (syncytia formation), often linked to pathogenesis. Thus membrane fusion is essential for both viral entry and cell-cell fusion and an attractive target for therapeutic development. While there are important differences between viral-cell and cell-cell membrane fusion, many aspects are conserved. The paramyxoviruses generally utilize two envelope glycoproteins to orchestrate membrane fusion. Here, we discuss the roles of these glycoproteins in distinct steps of the membrane fusion process. These findings can offer insights into evolutionary relationships among Paramyxoviridae genera and offer future targets for prophylactic and therapeutic development.

Timing is everything: Fine-tuned molecular machines orchestrate paramyxovirus entry

PubMed Central

Bose, Sayantan; Jardetzky, Theodore S.; Lamb, Robert A.

2015-01-01

The Paramyxoviridae include some of the great and ubiquitous disease-causing viruses of humans and animals. In most paramyxoviruses, two viral membrane glycoproteins, fusion protein (F) and receptor binding protein (HN, H or G) mediate a concerted process of recognition of host cell surface molecules followed by fusion of viral and cellular membranes, resulting in viral nucleocapsid entry into the cytoplasm. The interactions between the F and HN, H or G viral glycoproteins and host molecules are critical in determining host range, virulence and spread of these viruses. Recently, atomic structures, together with biochemical and biophysical studies, have provided major insights into how these two viral glycoproteins successfully interact with host receptors on cellular membranes and initiate the membrane fusion process to gain entry into cells. These studies highlight the conserved core mechanisms of paramyxovirus entry that provide the fundamental basis for rational anti-viral drug design and vaccine development. PMID:25771804

Paramyxovirus Glycoproteins and the Membrane Fusion Process

PubMed Central

Aguilar, Hector C.; Henderson, Bryce A.; Zamora, J. Lizbeth; Johnston, Gunner P.

2016-01-01

The family Paramyxoviridae includes many viruses that significantly affect human and animal health. An essential step in the paramyxovirus life cycle is viral entry into host cells, mediated by virus-cell membrane fusion. Upon viral entry, infection results in expression of the paramyxoviral glycoproteins on the infected cell surface. This can lead to cell-cell fusion (syncytia formation), often linked to pathogenesis. Thus membrane fusion is essential for both viral entry and cell-cell fusion and an attractive target for therapeutic development. While there are important differences between viral-cell and cell-cell membrane fusion, many aspects are conserved. The paramyxoviruses generally utilize two envelope glycoproteins to orchestrate membrane fusion. Here, we discuss the roles of these glycoproteins in distinct steps of the membrane fusion process. These findings can offer insights into evolutionary relationships among Paramyxoviridae genera and offer future targets for prophylactic and therapeutic development. PMID:28138419

Activation and synchronization of the oscillatory morphodynamics in multicellular monolayer

PubMed Central

Lin, Shao-Zhen; Li, Bo; Lan, Ganhui; Feng, Xi-Qiao

2017-01-01

Oscillatory morphodynamics provides necessary mechanical cues for many multicellular processes. Owing to their collective nature, these processes require robustly coordinated dynamics of individual cells, which are often separated too distantly to communicate with each other through biomaterial transportation. Although it is known that the mechanical balance generally plays a significant role in the systems’ morphologies, it remains elusive whether and how the mechanical components may contribute to the systems’ collective morphodynamics. Here, we study the collective oscillations in the Drosophila amnioserosa tissue to elucidate the regulatory roles of the mechanical components. We identify that the tensile stress is the key activator that switches the collective oscillations on and off. This regulatory role is shown analytically using the Hopf bifurcation theory. We find that the physical properties of the tissue boundary are directly responsible for synchronizing the oscillatory intensity and polarity of all inner cells and for orchestrating the spatial oscillation patterns inthe tissue. PMID:28716911

Proteomic biomarkers in lung cancer.

PubMed

Pastor, M D; Nogal, A; Molina-Pinelo, S; Carnero, A; Paz-Ares, L

2013-09-01

The correct understanding of tumour development relies on the comprehensive study of proteins. They are the main orchestrators of vital processes, such as signalling pathways, which drive the carcinogenic process. Proteomic technologies can be applied to cancer research to detect differential protein expression and to assess different responses to treatment. Lung cancer is the number one cause of cancer-related death in the world. Mostly diagnosed at late stages of the disease, lung cancer has one of the lowest 5-year survival rates at 15 %. The use of different proteomic techniques such as two-dimensional gel electrophoresis (2D-PAGE), isotope labelling (ICAT, SILAC, iTRAQ) and mass spectrometry may yield new knowledge on the underlying biology of lung cancer and also allow the development of new early detection tests and the identification of changes in the cancer protein network that are associated with prognosis and drug resistance.

Detection of human Dicer and Argonaute 2 catalytic activity

PubMed Central

Perron, Marjorie P.; Landry, Patricia; Plante, Isabelle; Provost, Patrick

2013-01-01

The microRNA (miRNA)-guided RNA silencing pathway is a central and well-defined cellular process involved in messenger RNA (mRNA) translational control. This complex regulatory process is achieved by a well orchestrated machinery composed of a relatively few protein components, among which the ribonuclease III (RNase III) Dicer and Argonaute 2 (Ago2) play a central role. These two proteins are essential and it is of particular interest to measure and detect their catalytic activity under various situations and/or conditions. In this chapter, we describe different protocols that aim to study and determine the catalytic activity of Dicer and Ago2 in cell extracts, immune complexes and size-fractionated cell extracts. Another protocol aimed at assessing miRNA binding to Ago2 is also described. These experimental approaches are likely to be useful to researchers investigating the main steps of miRNA biogenesis and function in human health and diseases. PMID:21528451

Virtually Out of This World!

NASA Technical Reports Server (NTRS)

2002-01-01

Ames Research Center granted Reality Capture Technologies (RCT), Inc., a license to further develop NASA's Mars Map software platform. The company incorporated NASA#s innovation into software that uses the Virtual Plant Model (VPM)(TM) to structure, modify, and implement the construction sites of industrial facilities, as well as develop, validate, and train operators on procedures. The VPM orchestrates the exchange of information between engineering, production, and business transaction systems. This enables users to simulate, control, and optimize work processes while increasing the reliability of critical business decisions. Engineers can complete the construction process and test various aspects of it in virtual reality before building the actual structure. With virtual access to and simulation of the construction site, project personnel can manage, access control, and respond to changes on complex constructions more effectively. Engineers can also create operating procedures, training, and documentation. Virtual Plant Model(TM) is a trademark of Reality Capture Technologies, Inc.

Predictive Modeling and Computational Toxicology

EPA Science Inventory

Embryonic development is orchestrated via a complex series of cellular interactions controlling behaviors such as mitosis, migration, differentiation, adhesion, contractility, apoptosis, and extracellular matrix remodeling. Any chemical exposure that perturbs these cellular proce...

Music Careers

ERIC Educational Resources Information Center

Alfaro, Daniel

1977-01-01

Careers in the music field for Hispanos are available for the industrious, competitive, and talented person. Among the careers are: composer, orchestrator-arranger, church musician, conductor, teacher, music librarian, tuner-technician, copyist, and instrument repairer. (NQ)

Redox-mediated activation of latent transforming growth factor-beta 1

NASA Technical Reports Server (NTRS)

Barcellos-Hoff, M. H.; Dix, T. A.; Chatterjee, A. (Principal Investigator)

1996-01-01

Transforming growth factor beta 1 (TGF beta) is a multifunctional cytokine that orchestrates response to injury via ubiquitous cell surface receptors. The biological activity of TGF beta is restrained by its secretion as a latent complex (LTGF beta) such that activation determines the extent of TGF beta activity during physiological and pathological events. TGF beta action has been implicated in a variety of reactive oxygen-mediated tissue processes, particularly inflammation, and in pathologies such as reperfusion injury, rheumatoid arthritis, and atherosclerosis. It was recently shown to be rapidly activated after in vivo radiation exposure, which also generates reactive oxygen species (ROS). In the present studies, the potential for redox-mediated LTGF beta activation was investigated using a cell-free system in which ROS were generated in solution by ionizing radiation or metal ion-catalyzed ascorbate reaction. Irradiation (100 Gray) of recombinant human LTGF beta in solution induced 26% activation compared with that elicited by standard thermal activation. Metal-catalyzed ascorbate oxidation elicited extremely efficient recombinant LTGF beta activation that matched or exceeded thermal activation. The efficiency of ascorbate activation depended on ascorbate concentrations and the presence of transition metal ions. We postulate that oxidation of specific amino acids in the latency-conferring peptide leads to a conformation change in the latent complex that allows release of TGF beta. Oxidative activation offers a novel route for the involvement of TGF beta in tissue processes in which ROS are implicated and endows LTGF beta with the ability to act as a sensor of oxidative stress and, by releasing TGF beta, to function as a signal for orchestrating the response of multiple cell types. LTGF beta redox sensitivity is presumably directed toward recovery of homeostasis; however, oxidation may also be a mechanism of LTGF beta activation that can be deleterious during disease mechanisms involving chronic ROS production.

The Best of Both Worlds: Developing a Hybrid Data System for the ASF DAAC

NASA Astrophysics Data System (ADS)

Arko, S. A.; Buechler, B.; Wolf, V. G.

2017-12-01

The Alaska Satellite Facility (ASF) at the University of Alaska Fairbanks hosts the NASA Distributed Active Archive Center (DAAC) specializing in synthetic aperture radar (SAR). Historically, the ASF DAAC has hosted hardware on-premises and developed DAAC-specific software to operate, manage, and maintain the DAAC data system. In the past year, ASF DAAC has been moving many of the standard DAAC operations into the Amazon Web Services (AWS) cloud. This includes data ingest, basic pre-processing, archiving, and distribution within the AWS environment. While the cloud offers nearly unbounded capacity for expansion and a great host of services, there also can be unexpected and unplanned costs for such. Additionally, these costs can be difficult to forecast even with historic data usage patterns and models for future usage. In an effort to maximize the effectiveness of the DAAC data system, while still managing and accurately forecasting costs, ASF DAAC has developed a hybrid, cloud and on-premises, data system. The goal of this project is to make extensive use of the AWS cloud, and when appropriate, utilize on-premises resources to help constrain costs. This hybrid system attempts to mimic, on premises, a cloud environment using Kubernetes container orchestration in order that software can be run in either location with little change. Combined with hybrid data storage architecture, the new data system makes use of the great capacity of the cloud while maintaining an on-premises options. This presentation will describe the development of the hybrid data system, including the micro-services architecture and design, the container orchestration, and hybrid storage. Additional we will highlight the lessons learned through the development process, cost forecasting for current and future SAR-mission operations, and provide a discussion of the pros and cons of hybrid architectures versus all-cloud deployments. This development effort has led to a system that is capable and flexible for the future while allowing ASF DAAC to continue supporting the SAR community with the highest level of services.

Bacterial Hsp70 (DnaK) and mammalian Hsp70 interact differently with lipid membranes.

PubMed

Lopez, Victor; Cauvi, David M; Arispe, Nelson; De Maio, Antonio

2016-07-01

The cellular response to stress is orchestrated by the expression of a family of proteins termed heat shock proteins (hsp) that are involved in the stabilization of basic cellular processes to preserve cell viability and homeostasis. The bulk of hsp function occurs within the cytosol and subcellular compartments. However, some hsp have also been found outside cells released by an active mechanism independent of cell death. Extracellular hsp act as signaling molecules directed at activating a systemic response to stress. The export of hsp requires the translocation from the cytosol into the extracellular milieu across the plasma membrane. We have proposed that membrane insertion is the initial step in this export process. We investigated the interaction of the major inducible hsp from mammalian (Hsp70) and bacterial (DnaK) species with liposomes. We found that mammalian Hsp70 displayed a high specificity for negatively charged phospholipids, such as phosphatidyl serine, whereas DnaK interacted with all lipids tested regardless of the charge. Both proteins were inserted into the lipid bilayer as demonstrated by resistance to acid or basic washes that was confirmed by partial protection from proteolytic cleavage. Several regions of mammalian Hsp70 were inserted into the membrane with a small portion of the N-terminus end exposed to the outer phase of the liposome. In contrast, the N-terminus end of DnaK was inserted into the membrane, exposing the C-terminus end outside the liposome. Mammalian Hsp70 was found to make high oligomeric complexes upon insertion into the membranes whereas DnaK only formed dimers within the lipid bilayer. These observations suggest that both Hsp70s interact with lipids, but mammalian Hsp70 displays a high degree of specificity and structure as compared with the bacterial form.

REACTOR - a Concept for establishing a System-of-Systems

NASA Astrophysics Data System (ADS)

Haener, Rainer; Hammitzsch, Martin; Wächter, Joachim

2014-05-01

REACTOR is a working title for activities implementing reliable, emergent, adaptive, and concurrent collaboration on the basis of transactional object repositories. It aims at establishing federations of autonomous yet interoperable systems (Systems-of-Systems), which are able to expose emergent behaviour. Following the principles of event-driven service-oriented architectures (SOA 2.0), REACTOR enables adaptive re-organisation by dynamic delegation of responsibilities and novel yet coherent monitoring strategies by combining information from different domains. Thus it allows collaborative decision-processes across system, discipline, and administrative boundaries. Interoperability is based on two approaches that implement interconnection and communication between existing heterogeneous infrastructures and information systems: Coordinated (orchestration-based) communication and publish/subscribe (choreography-based) communication. Choreography-based communication ensures the autonomy of the participating systems to the highest possible degree but requires the implementation of adapters, which provide functional access to information (publishing/consuming events) via a Message Oriented Middleware (MOM). Any interconnection of the systems (composition of service and message cascades) is established on the basis of global conversations that are enacted by choreographies specifying the expected behaviour of the participating systems with respect to agreed Service Level Agreements (SLA) required by e.g. national authorities. The specification of conversations, maintained in commonly available repositories also enables the utilisation of systems for purposes (evolving) other than initially intended. Orchestration-based communication additionally requires a central component that controls the information transfer via service requests or event processing and also takes responsibility of managing business processes. Commonly available transactional object repositories are well suited to establish brokers, which mediate metadata and semantic information about the resources of all involved systems. This concept has been developed within the project Collaborative, Complex, and Critical Decision-Support in Evolving Crises (TRIDEC) on the basis of semantic registries describing all facets of events and services utilisable for crisis management systems. The implementation utilises an operative infrastructure including an Enterprise Service Bus (ESB), adapters to proprietary sensor systems, a workflow engine, and a broker-based MOM. It also applies current technologies like actor-based frameworks for highly concurrent, distributed, and fault tolerant event-driven applications. Therefore REACTOR implementations are well suited to be hosted in a cloud that provides Infrastructure as a Service (IaaS). To provide low entry barriers for legacy and future systems, REACTOR adapts the principles of Design by Contract (DbC) as well as standardised and common information models like the Sensor Web Enablement (SWE) or the JavaScript Object Notation for geographic features (GeoJSON). REACTOR has been applied exemplarily within two different scenarios, Natural Crisis Management and Industrial Subsurface Development.

Advances of Stem Cell Therapeutics in Cutaneous Wound Healing and Regeneration.

PubMed

Kanji, Suman; Das, Hiranmoy

2017-01-01

Cutaneous wound healing is a complex multiple phase process, which overlaps each other, where several growth factors, cytokines, chemokines, and various cells interact in a well-orchestrated manner. However, an imbalance in any of these phases and factors may lead to disruption in harmony of normal wound healing process, resulting in transformation towards chronic nonhealing wounds and abnormal scar formation. Although various therapeutic interventions are available to treat chronic wounds, current wound-care has met with limited success. Progenitor stem cells possess potential therapeutic ability to overcome limitations of the present treatments as it offers accelerated wound repair with tissue regeneration. A substantial number of stem cell therapies for cutaneous wounds are currently under development as a result of encouraging preliminary findings in both preclinical and clinical studies. However, the mechanisms by which these stem cells contribute to the healing process have yet to be elucidated. In this review, we emphasize on the major treatment modalities currently available for the treatment of the wound, role of various interstitial stem cells and exogenous adult stem cells in cutaneous wound healing, and possible mechanisms involved in the healing process.

Selective attention modulates high-frequency activity in the face-processing network.

PubMed

Müsch, Kathrin; Hamamé, Carlos M; Perrone-Bertolotti, Marcela; Minotti, Lorella; Kahane, Philippe; Engel, Andreas K; Lachaux, Jean-Philippe; Schneider, Till R

2014-11-01

Face processing depends on the orchestrated activity of a large-scale neuronal network. Its activity can be modulated by attention as a function of task demands. However, it remains largely unknown whether voluntary, endogenous attention and reflexive, exogenous attention to facial expressions equally affect all regions of the face-processing network, and whether such effects primarily modify the strength of the neuronal response, the latency, the duration, or the spectral characteristics. We exploited the good temporal and spatial resolution of intracranial electroencephalography (iEEG) and recorded from depth electrodes to uncover the fast dynamics of emotional face processing. We investigated frequency-specific responses and event-related potentials (ERP) in the ventral occipito-temporal cortex (VOTC), ventral temporal cortex (VTC), anterior insula, orbitofrontal cortex (OFC), and amygdala when facial expressions were task-relevant or task-irrelevant. All investigated regions of interest (ROI) were clearly modulated by task demands and exhibited stronger changes in stimulus-induced gamma band activity (50-150 Hz) when facial expressions were task-relevant. Observed latencies demonstrate that the activation is temporally coordinated across the network, rather than serially proceeding along a processing hierarchy. Early and sustained responses to task-relevant faces in VOTC and VTC corroborate their role for the core system of face processing, but they also occurred in the anterior insula. Strong attentional modulation in the OFC and amygdala (300 msec) suggests that the extended system of the face-processing network is only recruited if the task demands active face processing. Contrary to our expectation, we rarely observed differences between fearful and neutral faces. Our results demonstrate that activity in the face-processing network is susceptible to the deployment of selective attention. Moreover, we show that endogenous attention operates along the whole face-processing network, and that these effects are reflected in frequency-specific changes in the gamma band. Copyright © 2014 Elsevier Ltd. All rights reserved.

Metaphors, models and organisational ethics in health care

PubMed Central

McCrickerd, J.

2000-01-01

Crucial to discussions in organisational ethics is an evaluation of the metaphors and models we use to understand the organisations we are discussing. I briefly defend this contention and evaluate three possible models: the current corporate model, an orchestrator model which puts hospitals in the same class as malls and airports, and a community model. I argue that the corporate and orchestrator model push to the background some important organisational ethics issues and bias us inappropriately towards certain solutions. Furthermore, I argue that the community model allows these to be more easily brought up. I also respond to the likely challenge that hospitals really are corporations by arguing that this is not relevant to evaluations of the appropriateness of the corporate model. Key Words: Metaphor • model • organisational ethics • health care ethics PMID:11055036

Electro-mechanical probe positioning system for large volume plasma device

NASA Astrophysics Data System (ADS)

Sanyasi, A. K.; Sugandhi, R.; Srivastava, P. K.; Srivastav, Prabhakar; Awasthi, L. M.

2018-05-01

An automated electro-mechanical system for the positioning of plasma diagnostics has been designed and implemented in a Large Volume Plasma Device (LVPD). The system consists of 12 electro-mechanical assemblies, which are orchestrated using the Modbus communication protocol on 4-wire RS485 communications to meet the experimental requirements. Each assembly has a lead screw-based mechanical structure, Wilson feed-through-based vacuum interface, bipolar stepper motor, micro-controller-based stepper drive, and optical encoder for online positioning correction of probes. The novelty of the system lies in the orchestration of multiple drives on a single interface, fabrication and installation of the system for a large experimental device like the LVPD, in-house developed software, and adopted architectural practices. The paper discusses the design, description of hardware and software interfaces, and performance results in LVPD.

A UV-B-specific signaling component orchestrates plant UV protection

PubMed Central

Brown, Bobby A.; Cloix, Catherine; Jiang, Guang Huai; Kaiserli, Eirini; Herzyk, Pawel; Kliebenstein, Daniel J.; Jenkins, Gareth I.

2005-01-01

UV-B radiation in sunlight has diverse effects on humans, animals, plants, and microorganisms. UV-B can cause damage to molecules and cells, and consequently organisms need to protect against and repair UV damage to survive in sunlight. In plants, low nondamaging levels of UV-B stimulate transcription of genes involved in UV-protective responses. However, remarkably little is known about the underlying mechanisms of UV-B perception and signal transduction. Here we report that Arabidopsis UV RESISTANCE LOCUS 8 (UVR8) is a UV-B-specific signaling component that orchestrates expression of a range of genes with vital UV-protective functions. Moreover, we show that UVR8 regulates expression of the transcription factor HY5 specifically when the plant is exposed to UV-B. We demonstrate that HY5 is a key effector of the UVR8 pathway, and that it is required for survival under UV-B radiation. UVR8 has sequence similarity to the eukaryotic guanine nucleotide exchange factor RCC1, but we found that it has little exchange activity. However, UVR8, like RCC1, is located principally in the nucleus and associates with chromatin via histones. Chromatin immunoprecipitation showed that UVR8 associates with chromatin in the HY5 promoter region, providing a mechanistic basis for its involvement in regulating transcription. We conclude that UVR8 defines a UV-B-specific signaling pathway in plants that orchestrates the protective gene expression responses to UV-B required for plant survival in sunlight. PMID:16330762

Music, emotion, and time perception: the influence of subjective emotional valence and arousal?

PubMed Central

Droit-Volet, Sylvie; Ramos, Danilo; Bueno, José L. O.; Bigand, Emmanuel

2013-01-01

The present study used a temporal bisection task with short (<2 s) and long (>2 s) stimulus durations to investigate the effect on time estimation of several musical parameters associated with emotional changes in affective valence and arousal. In order to manipulate the positive and negative valence of music, Experiments 1 and 2 contrasted the effect of musical structure with pieces played normally and backwards, which were judged to be pleasant and unpleasant, respectively. This effect of valence was combined with a subjective arousal effect by changing the tempo of the musical pieces (fast vs. slow) (Experiment 1) or their instrumentation (orchestral vs. piano pieces). The musical pieces were indeed judged more arousing with a fast than with a slow tempo and with an orchestral than with a piano timbre. In Experiment 3, affective valence was also tested by contrasting the effect of tonal (pleasant) vs. atonal (unpleasant) versions of the same musical pieces. The results showed that the effect of tempo in music, associated with a subjective arousal effect, was the major factor that produced time distortions with time being judged longer for fast than for slow tempi. When the tempo was held constant, no significant effect of timbre on the time judgment was found although the orchestral music was judged to be more arousing than the piano music. Nevertheless, emotional valence did modulate the tempo effect on time perception, the pleasant music being judged shorter than the unpleasant music. PMID:23882233

The formation and distribution of hippocampal synapses on patterned neuronal networks

NASA Astrophysics Data System (ADS)

Dowell-Mesfin, Natalie M.

Communication within the central nervous system is highly orchestrated with neurons forming trillions of specialized junctions called synapses. In vivo, biochemical and topographical cues can regulate neuronal growth. Biochemical cues also influence synaptogenesis and synaptic plasticity. The effects of topography on the development of synapses have been less studied. In vitro, neuronal growth is unorganized and complex making it difficult to study the development of networks. Patterned topographical cues guide and control the growth of neuronal processes (axons and dendrites) into organized networks. The aim of this dissertation was to determine if patterned topographical cues can influence synapse formation and distribution. Standard fabrication and compression molding procedures were used to produce silicon masters and polystyrene replicas with topographical cues presented as 1 mum high pillars with diameters of 0.5 and 2.0 mum and gaps of 1.0 to 5.0 mum. Embryonic rat hippocampal neurons grown unto patterned surfaces. A developmental analysis with immunocytochemistry was used to assess the distribution of pre- and post-synaptic proteins. Activity-dependent pre-synaptic vesicle uptake using functional imaging dyes was also performed. Adaptive filtering computer algorithms identified synapses by segmenting juxtaposed pairs of pre- and post-synaptic labels. Synapse number and area were automatically extracted from each deconvolved data set. In addition, neuronal processes were traced automatically to assess changes in synapse distribution. The results of these experiments demonstrated that patterned topographic cues can induce organized and functional neuronal networks that can serve as models for the study of synapse formation and plasticity as well as for the development of neuroprosthetic devices.

Tensile forces drive a reversible fibroblast-to-myofibroblast transition during tissue growth in engineered clefts

PubMed Central

Kollmannsberger, Philip; Bidan, Cécile M.; Dunlop, John W. C.; Fratzl, Peter; Vogel, Viola

2018-01-01

Myofibroblasts orchestrate wound healing processes, and if they remain activated, they drive disease progression such as fibrosis and cancer. Besides growth factor signaling, the local extracellular matrix (ECM) and its mechanical properties are central regulators of these processes. It remains unknown whether transforming growth factor–β (TGF-β) and tensile forces work synergistically in up-regulating the transition of fibroblasts into myofibroblasts and whether myofibroblasts undergo apoptosis or become deactivated by other means once tissue homeostasis is reached. We used three-dimensional microtissues grown in vitro from fibroblasts in macroscopically engineered clefts for several weeks and found that fibroblasts transitioned into myofibroblasts at the highly tensed growth front as the microtissue progressively closed the cleft, in analogy to closing a wound site. Proliferation was up-regulated at the growth front, and new highly stretched fibronectin fibers were deposited, as revealed by fibronectin fluorescence resonance energy transfer probes. As the tissue was growing, the ECM underneath matured into a collagen-rich tissue containing mostly fibroblasts instead of myofibroblasts, and the fibronectin fibers were under reduced tension. This correlated with a progressive rounding of cells from the growth front inward, with decreased α–smooth muscle actin expression, YAP nuclear translocation, and cell proliferation. Together, this suggests that the myofibroblast phenotype is stabilized at the growth front by tensile forces, even in the absence of endogenously supplemented TGF-β, and reverts into a quiescent fibroblast phenotype already 10 μm behind the growth front, thus giving rise to a myofibroblast-to-fibroblast transition. This is the hallmark of reaching prohealing homeostasis. PMID:29349300

Actin Age Orchestrates Myosin-5 and Myosin-6 Runlengths

PubMed Central

Zimmermann, Dennis; Santos, Alicja; Kovar, David R.; Rock, Ronald S.

2015-01-01

Summary Unlike a static and immobile skeleton, the actin cytoskeleton is a highly dynamic network of filamentous actin (F-actin) polymers that continuously turn over. In addition to generating mechanical forces and sensing mechanical deformation, dynamic F-actin networks serve as cellular tracks for myosin motor traffic. However, much of our mechanistic understanding of processive myosins comes from in vitro studies where motility was studied on pre-assembled and artificially stabilized, static F-actin tracks. In this work, we examine the role of actin dynamics in single-molecule myosin motility using assembling F-actin and the two highly processive motors, myosin-5 and myosin-6. These two myosins have distinct functions in the cell and travel in opposite directions along actin filaments [1–3]. Myosin-5 walks towards the barbed ends of F-actin, traveling to sites of actin polymerization at the cell periphery [4]. Myosin-6 walks towards the pointed end of F-actin [5], traveling towards the cell center along older segments of the actin filament. We find that myosin-5 takes 1.3 to 1.5-fold longer runs on ADP•Pi (young) F-actin, while myosin-6 takes 1.7 to 3.6-fold longer runs along ADP (old) F-actin. These results suggest that conformational differences between ADP•Pi and ADP F-actin tailor these myosins to walk farther toward their preferred actin filament end. Taken together, these experiments define a new mechanism by which myosin traffic may sort to different F-actin networks depending on filament age. PMID:26190073

Toward a Low-Cost System for High-Throughput Image-Based Phenotyping of Root System Architecture

NASA Astrophysics Data System (ADS)

Davis, T. W.; Schneider, D. J.; Cheng, H.; Shaw, N.; Kochian, L. V.; Shaff, J. E.

2015-12-01

Root system architecture is being studied more closely for improved nutrient acquisition, stress tolerance and carbon sequestration by relating the genetic material that corresponds to preferential physical features. This information can help direct plant breeders in addressing the growing concerns regarding the global demand on crops and fossil fuels. To help support this incentive comes a need to make high-throughput image-based phenotyping of plant roots, at the individual plant scale, simpler and more affordable. Our goal is to create an affordable and portable product for simple image collection, processing and management that will extend root phenotyping to institutions with limited funding (e.g., in developing countries). Thus, a new integrated system has been developed using the Raspberry Pi single-board computer. Similar to other 3D-based imaging platforms, the system utilizes a stationary camera to photograph a rotating crop root system (e.g., rice, maize or sorghum) that is suspended either in a gel or on a mesh (for hydroponics). In contrast, the new design takes advantage of powerful open-source hardware and software to reduce the system costs, simplify the imaging process, and manage the large datasets produced by the high-resolution photographs. A newly designed graphical user interface (GUI) unifies the system controls (e.g., adjusting camera and motor settings and orchestrating the motor motion with image capture), making it easier to accommodate a variety of experiments. During each imaging session, integral metadata necessary for reproducing experiment results are collected (e.g., plant type and age, growing conditions and treatments, camera settings) using hierarchical data format files. These metadata are searchable within the GUI and can be selected and extracted for further analysis. The GUI also supports an image previewer that performs limited image processing (e.g., thresholding and cropping). Root skeletonization, 3D reconstruction and trait calculation (e.g., rooting depth, rooting angle, total volume of roots) is being developed in conjunction with this project.

Cortactin deficiency is associated with reduced neutrophil recruitment but increased vascular permeability in vivo.

PubMed

Schnoor, Michael; Lai, Frank P L; Zarbock, Alexander; Kläver, Ruth; Polaschegg, Christian; Schulte, Dörte; Weich, Herbert A; Oelkers, J Margit; Rottner, Klemens; Vestweber, Dietmar

2011-08-01

Neutrophil extravasation and the regulation of vascular permeability require dynamic actin rearrangements in the endothelium. In this study, we analyzed in vivo whether these processes require the function of the actin nucleation-promoting factor cortactin. Basal vascular permeability for high molecular weight substances was enhanced in cortactin-deficient mice. Despite this leakiness, neutrophil extravasation in the tumor necrosis factor-stimulated cremaster was inhibited by the loss of cortactin. The permeability defect was caused by reduced levels of activated Rap1 (Ras-related protein 1) in endothelial cells and could be rescued by activating Rap1 via the guanosine triphosphatase (GTPase) exchange factor EPAC (exchange protein directly activated by cAMP). The defect in neutrophil extravasation was caused by enhanced rolling velocity and reduced adhesion in postcapillary venules. Impaired rolling interactions were linked to contributions of β(2)-integrin ligands, and firm adhesion was compromised by reduced ICAM-1 (intercellular adhesion molecule 1) clustering around neutrophils. A signaling process known to be critical for the formation of ICAM-1-enriched contact areas and for transendothelial migration, the ICAM-1-mediated activation of the GTPase RhoG was blocked in cortactin-deficient endothelial cells. Our results represent the first physiological evidence that cortactin is crucial for orchestrating the molecular events leading to proper endothelial barrier function and leukocyte recruitment in vivo.

Spatial and temporal transcriptome changes occurring during flower opening and senescence of the ephemeral hibiscus flower, Hibiscus rosa-sinensis.

PubMed

Trivellini, Alice; Cocetta, Giacomo; Hunter, Donald A; Vernieri, Paolo; Ferrante, Antonio

2016-10-01

Flowers are complex systems whose vegetative and sexual structures initiate and die in a synchronous manner. The rapidity of this process varies widely in flowers, with some lasting for months while others such as Hibiscus rosa-sinensis survive for only a day. The genetic regulation underlying these differences is unclear. To identify key genes and pathways that coordinate floral organ senescence of ephemeral flowers, we identified transcripts in H. rosa-sinensis floral organs by 454 sequencing. During development, 2053 transcripts increased and 2135 decreased significantly in abundance. The senescence of the flower was associated with increased abundance of many hydrolytic genes, including aspartic and cysteine proteases, vacuolar processing enzymes, and nucleases. Pathway analysis suggested that transcripts altering significantly in abundance were enriched in functions related to cell wall-, aquaporin-, light/circadian clock-, autophagy-, and calcium-related genes. Finding enrichment in light/circadian clock-related genes fits well with the observation that hibiscus floral development is highly synchronized with light and the hypothesis that ageing/senescence of the flower is orchestrated by a molecular clock. Further study of these genes will provide novel insight into how the molecular clock is able to regulate the timing of programmed cell death in tissues. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Ultradian metronome: timekeeper for orchestration of cellular coherence.

PubMed

Lloyd, David; Murray, Douglas B

2005-07-01

Dynamic intracellular spatial and temporal organization emerges from spontaneous synchronization of a massive array of weakly coupled oscillators; the majority of subcellular processes are implicated in this integrated expression of cellular physiology. Evidence for this view comes mainly from studies of Saccharomyces cerevisiae growing in self-synchronized continuous cultures, in which a temperature-compensated ultradian clock (period of approximately 40 min) couples fermentation with redox state in addition to the transcriptome and cell-division-cycle progression. Functions for ultradian clocks have also been determined in other yeasts (e.g. Schizosaccharomyces pombe and Candida utilis), seven protists (e.g. Acanthamoeba castellanii and Paramecium tetraurelia), as well as cultured mammalian cells. We suggest that ultradian timekeeping is a basic universal necessity for coordinated intracellular coherence.

Specialized Proresolving Mediators in Innate and Adaptive Immune Responses in Airway Diseases.

PubMed

Krishnamoorthy, Nandini; Abdulnour, Raja-Elie E; Walker, Katherine H; Engstrom, Braden D; Levy, Bruce D

2018-07-01

Airborne pathogens and environmental stimuli evoke immune responses in the lung. It is critical to health that these responses be controlled to prevent tissue damage and the compromise of organ function. Resolution of inflammation is a dynamic process that is coordinated by biochemical and cellular mechanisms. Recently, specialized proresolving mediators (SPMs) have been identified in resolution exudates. These molecules orchestrate anti-inflammatory and proresolving actions that are cell type specific. In this review, we highlight SPM biosynthesis, the influence of SPMs on the innate and adaptive immune responses in the lung, as well as recent insights from SPMs on inflammatory disease pathophysiology. Uncovering these mediators and cellular mechanisms for resolution is providing new windows into physiology and disease pathogenesis.

The role of the oncofetal H19 lncRNA in tumor metastasis: orchestrating the EMT-MET decision

PubMed Central

Matouk, Imad J.; Halle, David; Raveh, Eli; Gilon, Michal; Sorin, Vladimir; Hochberg, Avraham

2016-01-01

Long non-coding RNA (lncRNA) genes are emerging as key players in the metastatic cascade. Current evidence indicate that H19 lncRNA and the microRNA(miRNA) miR-675, which is processed from it, play crucial roles in metastasis, through the regulation of critical events specifically the epithelial to mesenchymal (EMT) and the mesenchymal to epithelial transitions (MET). This review summarizes recent mechanistic pathways and tries to put together seemingly conflicting data from different reports under one proposed general scheme underlying the various roles of H19/miR-675 in the metastatic cascade. We propose several approaches to harnessing this knowledge for translational medicine. PMID:26623562

Opinion: Interactions of innate and adaptive lymphocytes

PubMed Central

Gasteiger, Georg; Rudensky, Alexander Y.

2015-01-01

Innate lymphocytes, including natural killer (NK) cells and the recently discovered innate lymphoid cells (ILCs) have crucial roles during infection, tissue injury and inflammation. Innate signals regulate the activation and homeostasis of innate lymphocytes. Less well understood is the contribution of the adaptive immune system to the orchestration of innate lymphocyte responses. We review our current understanding of the interactions between adaptive and innate lymphocytes, and propose a model in which adaptive T cells function as antigen-specific sensors for the activation of innate lymphocytes to amplify and instruct local immune responses. We highlight the potential role of regulatory and helper T cells in these processes and discuss major questions in the emerging area of crosstalk between adaptive and innate lymphocytes. PMID:25132095

Justification of automated decision-making: medical explanations as medical arguments.

PubMed Central

Shankar, R. D.; Musen, M. A.

1999-01-01

People use arguments to justify their claims. Computer systems use explanations to justify their conclusions. We are developing WOZ, an explanation framework that justifies the conclusions of a clinical decision-support system. WOZ's central component is the explanation strategy that decides what information justifies a claim. The strategy uses Toulmin's argument structure to define pieces of information and to orchestrate their presentation. WOZ uses explicit models that abstract the core aspects of the framework such as the explanation strategy. In this paper, we present the use of arguments, the modeling of explanations, and the explanation process used in WOZ. WOZ exploits the wealth of naturally occurring arguments, and thus can generate convincing medical explanations. Images Figure 5 PMID:10566388

Outsourcing neural active control to passive composite mechanics: a tissue engineered cyborg ray

NASA Astrophysics Data System (ADS)

Gazzola, Mattia; Park, Sung Jin; Park, Kyung Soo; Park, Shirley; di Santo, Valentina; Deisseroth, Karl; Lauder, George V.; Mahadevan, L.; Parker, Kevin Kit

2016-11-01

Translating the blueprint that stingrays and skates provide, we create a cyborg swimming ray capable of orchestrating adaptive maneuvering and phototactic navigation. The impossibility of replicating the neural system of batoids fish is bypassed by outsourcing algorithmic functionalities to the body composite mechanics, hence casting the active control problem into a design, passive one. We present a first step in engineering multilevel "brain-body-flow" systems that couple sensory information to motor coordination and movement, leading to behavior. This work paves the way for the development of autonomous and adaptive artificial creatures able to process multiple sensory inputs and produce complex behaviors in distributed systems and may represent a path toward soft-robotic "embodied cognition".

Orchestrating the Soundscape.

ERIC Educational Resources Information Center

Neill, William G.

1982-01-01

Suggests discussion questions, demonstrations, and activities related to a Public Broadcasting Service documentary ("To Hear"). The basic theme of the program is that people don't realize the dangers of excessive noise because it is pervasive and invisible. (Author/JN)

Information Integration and Communication in Plant Growth Regulation.

PubMed

Chaiwanon, Juthamas; Wang, Wenfei; Zhu, Jia-Ying; Oh, Eunkyoo; Wang, Zhi-Yong

2016-03-10

Plants are equipped with the capacity to respond to a large number of diverse signals, both internal ones and those emanating from the environment, that are critical to their survival and adaption as sessile organisms. These signals need to be integrated through highly structured intracellular networks to ensure coherent cellular responses, and in addition, spatiotemporal actions of hormones and peptides both orchestrate local cell differentiation and coordinate growth and physiology over long distances. Further, signal interactions and signaling outputs vary significantly with developmental context. This review discusses our current understanding of the integrated intracellular and intercellular signaling networks that control plant growth. Copyright © 2016 Elsevier Inc. All rights reserved.

High precision active nutation control for a flexible momentum biased spacecraft

NASA Technical Reports Server (NTRS)

Laskin, R. A.; Kopf, E. H.

1984-01-01

The controller design for the Solar Dynamics Observatory (SDO) is presented. SDO is a momentum biased spacecraft with three flexible appendages. Its primary scientific instrument, the solar oscillations imager (SOI), is rigidly attached to the spacecraft bus and has arc-second pointing requirements. Meeting these requirements necessitates the use of an active nutation controller (ANC) which is here mechanized with a small reaction wheel oriented along a bus transverse axis. The ANC does its job by orchestrating the transfer of angular momentum out of the bus transverse axes and into the momentum wheel. A simulation study verifies that the controller provides quick, stable, and accurate response.

On the road to bioartificial organs.

PubMed

Ren, X; Ott, H C

2014-10-01

Biological organs are highly orchestrated systems with well-coordinated positioning, grouping, and interaction of different cell types within their specialized extracellular environment. Bioartificial organs are intended to be functional replacements of native organs generated through bioengineering techniques and hold the potential to alleviate donor organ shortage for transplantation. The development, production, and evaluation of such bioartificial organs require synergistic efforts of biology, material science, engineering, and medicine. In this review, we highlight the emerging platforms enabling structured assembly of multiple cell types into functional grafts and discuss recent advances and challenges in the development of bioartificial organs, including cell sources, in vitro organ culture, in vivo evaluation, and clinical considerations.

Emerging Trends in the Discovery of Natural Product Antibacterials

PubMed Central

Bologa, Cristian G.; Ursu, Oleg; Oprea, Tudor; Melançon, Charles E.; Tegos, George P.

2013-01-01

This article highlights current trends and advances in exploiting natural sources for the deployment of novel and potent anti-infective countermeasures. The key challenge is to therapeutically target microbial pathogens exhibiting a variety of puzzling and evolutionary complex resistance mechanisms. Special emphasis is given to the strengths, weaknesses, and opportunities in the natural product antimicrobial drug discovery arena, and to emerging applications driven by advances in bioinformatics, chemical biology, and synthetic biology in concert with exploiting the microbial phenotype. These orchestrated efforts have identified a critical mass of lead natural antimicrobials chemical scaffolds and discovery technologies with high probability of successful implementation against emerging microbial pathogens. PMID:23890825

Information Integration and Communication in Plant Growth Regulation

PubMed Central

Chaiwanon, Juthamas; Wang, Wenfei; Zhu, Jia-Ying; Oh, Eunkyoo; Wang, Zhi-Yong

2016-01-01

Plants are equipped with the capacity to respond to a large number of diverse signals, both internal ones and those emanating from the environment, that are critical to their survival and adaption as sessile organisms. These signals need to be integrated through highly structured intracellular networks to ensure coherent cellular responses, and in addition, spatiotemporal actions of hormones and peptides both orchestrate local cell differentiation and coordinate growth and physiology over long distances. Further, signal interactions and signaling outputs vary significantly with developmental context. This review discusses our current understanding of the integrated intracellular and intercellular signaling networks that control plant growth. PMID:26967291

Ca2+ transport and signalling in enamel cells

PubMed Central

Nurbaeva, Meerim K.; Eckstein, Miriam; Feske, Stefan

2016-01-01

Abstract Dental enamel is one of the most remarkable examples of matrix‐mediated biomineralization. Enamel crystals form de novo in a rich extracellular environment in a stage‐dependent manner producing complex microstructural patterns that are visually stunning. This process is orchestrated by specialized epithelial cells known as ameloblasts which themselves undergo striking morphological changes, switching function from a secretory role to a cell primarily engaged in ionic transport. Ameloblasts are supported by a host of cell types which combined represent the enamel organ. Fully mineralized enamel is the hardest tissue found in vertebrates owing its properties partly to the unique mixture of ionic species represented and their highly organized assembly in the crystal lattice. Among the main elements found in enamel, Ca2+ is the most abundant ion, yet how ameloblasts modulate Ca2+ dynamics remains poorly known. This review describes previously proposed models for passive and active Ca2+ transport, the intracellular Ca2+ buffering systems expressed in ameloblasts and provides an up‐dated view of current models concerning Ca2+ influx and extrusion mechanisms, where most of the recent advances have been made. We also advance a new model for Ca2+ transport by the enamel organ. PMID:27510811

Ectopic Expression of JcWRKY Transcription Factor Confers Salinity Tolerance via Salicylic Acid Signaling.

PubMed

Agarwal, Parinita; Dabi, Mitali; Sapara, Komal K; Joshi, Priyanka S; Agarwal, Pradeep K

2016-01-01

Plants, being sessile, have developed intricate signaling network to specifically respond to the diverse environmental stress. The plant-specific WRKY TFs form one of the largest TF family and are involved in diverse plant processes, involving growth, development and stress signaling through auto and cross regulation with different genes and TFs. Here, we report the functional characterization of a salicylic acid -inducible JcWRKY TF. The JcWRKY overexpression confers salinity tolerance in transgenic tobacco, as was evident by increased chlorophyll content and seed germination potential. The transgenic plants showed increased soluble sugar, membrane stability, reduced electrolyte leakage and generation of reactive oxygen species (H 2 O 2 and [Formula: see text]) as compared to the wild type. Furthermore, the low SA treatment along with salinity improved the tolerance potential of the transgenics by maintaining ROS homeostasis and high K + /Na + ratio. The transcript expression of SA biosynthetic gene ICS1 and antioxidative enzymes ( CAT and SOD ) showed upregulation during stress. Thus, the present study reflects that JcWRKY is working in co-ordination with SA signaling to orchestrate the different biochemical and molecular pathways to maneuvre salt stress tolerance of the transgenic plants.

Identification of Regulatory DNA Elements Using Genome-wide Mapping of DNase I Hypersensitive Sites during Tomato Fruit Development.

PubMed

Qiu, Zhengkun; Li, Ren; Zhang, Shuaibin; Wang, Ketao; Xu, Meng; Li, Jiayang; Du, Yongchen; Yu, Hong; Cui, Xia

2016-08-01

Development and ripening of tomato fruit are precisely controlled by transcriptional regulation, which depends on the orchestrated accessibility of regulatory proteins to promoters and other cis-regulatory DNA elements. This accessibility and its effect on gene expression play a major role in defining the developmental process. To understand the regulatory mechanism and functional elements modulating morphological and anatomical changes during fruit development, we generated genome-wide high-resolution maps of DNase I hypersensitive sites (DHSs) from the fruit tissues of the tomato cultivar "Moneymaker" at 20 days post anthesis as well as break stage. By exploring variation of DHSs across fruit development stages, we pinpointed the most likely hypersensitive sites related to development-specific genes. By detecting binding motifs on DHSs of these development-specific genes or genes in the ascorbic acid biosynthetic pathway, we revealed the common regulatory elements contributing to coordinating gene transcription of plant ripening and specialized metabolic pathways. Our results contribute to a better understanding of the regulatory dynamics of genes involved in tomato fruit development and ripening. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

1993 Gordon Bell Prize Winners

NASA Technical Reports Server (NTRS)

Karp, Alan H.; Simon, Horst; Heller, Don; Cooper, D. M. (Technical Monitor)

1994-01-01

The Gordon Bell Prize recognizes significant achievements in the application of supercomputers to scientific and engineering problems. In 1993, finalists were named for work in three categories: (1) Performance, which recognizes those who solved a real problem in the quickest elapsed time. (2) Price/performance, which encourages the development of cost-effective supercomputing. (3) Compiler-generated speedup, which measures how well compiler writers are facilitating the programming of parallel processors. The winners were announced November 17 at the Supercomputing 93 conference in Portland, Oregon. Gordon Bell, an independent consultant in Los Altos, California, is sponsoring $2,000 in prizes each year for 10 years to promote practical parallel processing research. This is the sixth year of the prize, which Computer administers. Something unprecedented in Gordon Bell Prize competition occurred this year: A computer manufacturer was singled out for recognition. Nine entries reporting results obtained on the Cray C90 were received, seven of the submissions orchestrated by Cray Research. Although none of these entries showed sufficiently high performance to win outright, the judges were impressed by the breadth of applications that ran well on this machine, all nine running at more than a third of the peak performance of the machine.

Motor activity of centromere-associated protein-E contributes to its localization at the center of the midbody to regulate cytokinetic abscission

PubMed Central

Ohashi, Akihiro; Ohori, Momoko; Iwai, Kenichi

2016-01-01

Accurate control of cytokinesis is critical for genomic stability to complete high-fidelity transmission of genetic material to the next generation. A number of proteins accumulate in the intercellular bridge (midbody) during cytokinesis, and the dynamics of these proteins are temporally and spatially orchestrated to complete the process. In this study, we demonstrated that localization of centromere-associated protein-E (CENP-E) at the midbody is involved in cytokinetic abscission. The motor activity of CENP-E and the C-terminal midbody localization domain, which includes amino acids 2659–2666 (RYFDNSSL), are involved in the anchoring of CENP-E to the center of the midbody. Furthermore, CENP-E motor activity contributes to the accumulation of protein regulator of cytokinesis 1 (PRC1) in the midbody during cytokinesis. Midbody localization of PRC1 is critical to the antiparallel microtubule structure and recruitment of other midbody-associated proteins. Therefore, CENP-E motor activity appears to play important roles in the organization of these proteins to complete cytokinetic abscission. Our findings will be helpful for understanding how each step of cytokinesis is regulated to complete cytokinetic abscission. PMID:27835888

SARS-CoV fusion peptides induce membrane surface ordering and curvature.

PubMed

Basso, Luis G M; Vicente, Eduardo F; Crusca, Edson; Cilli, Eduardo M; Costa-Filho, Antonio J

2016-11-28

Viral membrane fusion is an orchestrated process triggered by membrane-anchored viral fusion glycoproteins. The S2 subunit of the spike glycoprotein from severe acute respiratory syndrome (SARS) coronavirus (CoV) contains internal domains called fusion peptides (FP) that play essential roles in virus entry. Although membrane fusion has been broadly studied, there are still major gaps in the molecular details of lipid rearrangements in the bilayer during fusion peptide-membrane interactions. Here we employed differential scanning calorimetry (DSC) and electron spin resonance (ESR) to gather information on the membrane fusion mechanism promoted by two putative SARS FPs. DSC data showed the peptides strongly perturb the structural integrity of anionic vesicles and support the hypothesis that the peptides generate opposing curvature stresses on phosphatidylethanolamine membranes. ESR showed that both FPs increase lipid packing and head group ordering as well as reduce the intramembrane water content for anionic membranes. Therefore, bending moment in the bilayer could be generated, promoting negative curvature. The significance of the ordering effect, membrane dehydration, changes in the curvature properties and the possible role of negatively charged phospholipids in helping to overcome the high kinetic barrier involved in the different stages of the SARS-CoV-mediated membrane fusion are discussed.

Parkinson Disease-linked Vps35 R524W Mutation Impairs the Endosomal Association of Retromer and Induces α-Synuclein Aggregation.

PubMed

Follett, Jordan; Bugarcic, Andrea; Yang, Zhe; Ariotti, Nicholas; Norwood, Suzanne J; Collins, Brett M; Parton, Robert G; Teasdale, Rohan D

2016-08-26

Endosomal sorting is a highly orchestrated cellular process. Retromer is a heterotrimeric complex that associates with endosomal membranes and facilitates the retrograde sorting of multiple receptors, including the cation-independent mannose 6-phosphate receptor for lysosomal enzymes. The cycling of retromer on and off the endosomal membrane is regulated by a network of retromer-interacting proteins. Here, we find that Parkinson disease-associated Vps35 variant, R524W, but not P316S, is a loss-of-function mutation as marked by a reduced association with this regulatory network and dysregulation of endosomal receptor sorting. Expression of Vps35 R524W-containing retromer results in the accumulation of intracellular α-synuclein-positive aggregates, a hallmark of Parkinson disease. Overall, the Vps35 R524W-containing retromer has a decreased endosomal association, which can be partially rescued by R55, a small molecule previously shown to stabilize the retromer complex, supporting the potential for future targeting of the retromer complex in the treatment of Parkinson disease. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Structural Basis of Interaction between Urokinase-Type Plasminogen Activator and Its Receptor

PubMed Central

Barinka, Cyril; Parry, Graham; Callahan, Jennifer; Shaw, David E.; Kuo, Alice; Bdeir, Khalil; Cines, Douglas B.; Mazar, Andrew; Lubkowski, Jacek

2009-01-01

Summary Recent studies indicate that binding of urokinase-type plasminogen activator (uPA) to its high affinity receptor (uPAR), orchestrates uPAR interactions with other cellular components that play a pivotal role in diverse (patho-)physiological processes including wound healing, angiogenesis, inflammation, and cancer metastasis. However, notwithstanding the wealth of biochemical data available describing the activities of uPAR, little is known as to the exact mode of uPAR-uPA interactions and the presumed conformational changes that accompanying uPA-uPAR engagement. Here we report the crystal structure of soluble urokinase plasminogen activator receptor (suPAR), which contains the three domains of the wild-type receptor but lacks the cell surface anchoring sequence, in complex with the amino terminal fragment of urokinase-type plasminogen activator (ATF), at the resolution of 2.8 Å. We also report the 1.9 Å crystal structure of the free ATF. Our results provide a structural basis, represented by conformational changes induced in uPAR, for several published biochemical observations describing the nature of uPAR-uPA interactions and provide insight into mechanisms that may be responsible for the cellular responses induced by uPA binding. PMID:16979660

Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella

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

Yoon, Hyunjin; Ansong, Charles; McDermott, Jason E.

Background: Systemic bacterial infections are highly regulated and complex processes that are orchestrated by numerous virulence factors. Genes that are coordinately controlled by the set of regulators required for systemic infection are potentially required for pathogenicity. Results: In this study we present a systems biology approach in which sample-matched multi-omic measurements of fourteen virulence-essential regulator mutants were coupled with computational network analysis to efficiently identify Salmonella virulence factors. Immunoblot experiments verified network-predicted virulence factors and a subset was determined to be secreted into the host cytoplasm, suggesting that they are virulence factors directly interacting with host cellular components. Two ofmore » these, SrfN and PagK2, were required for full mouse virulence and were shown to be translocated independent of either of the type III secretion systems in Salmonella or the type III injectisome-related flagellar mechanism. Conclusions: Integrating multi-omic datasets from Salmonella mutants lacking virulence regulators not only identified novel virulence factors but also defined a new class of translocated effectors involved in pathogenesis. The success of this strategy at discovery of known and novel virulence factors suggests that the approach may have applicability for other bacterial pathogens.« less

MicroRNA-146a governs fibroblast activation and joint pathology in arthritis.

PubMed

Saferding, Victoria; Puchner, Antonia; Goncalves-Alves, Eliana; Hofmann, Melanie; Bonelli, Michael; Brunner, Julia S; Sahin, Emine; Niederreiter, Birgit; Hayer, Silvia; Kiener, Hans P; Einwallner, Elisa; Nehmar, Ramzi; Carapito, Raphael; Georgel, Philippe; Koenders, Marije I; Boldin, Mark; Schabbauer, Gernot; Kurowska-Stolarska, Mariola; Steiner, Günter; Smolen, Josef S; Redlich, Kurt; Blüml, Stephan

2017-08-01

Synovial fibroblasts are key cells orchestrating the inflammatory response in arthritis. Here we demonstrate that loss of miR-146a, a key epigenetic regulator of the innate immune response, leads to increased joint destruction in a TNF-driven model of arthritis by specifically regulating the behavior of synovial fibroblasts. Absence of miR-146a in synovial fibroblasts display a highly deregulated gene expression pattern and enhanced proliferation in vitro and in vivo. Deficiency of miR-146a induces deregulation of tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) in synovial fibroblasts, leading to increased proliferation. In addition, loss of miR-146a shifts the metabolic state of fibroblasts towards glycolysis and augments the ability of synovial fibroblasts to support the generation of osteoclasts by controlling the balance of osteoclastogenic regulatory factors receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG). Bone marrow transplantation experiments confirmed the importance of miR-146a in the radioresistant mesenchymal compartment for the control of arthritis severity, in particular for inflammatory joint destruction. This study therefore identifies microRNA-146a as an important local epigenetic regulator of the inflammatory response in arthritis. It is a central element of an anti-inflammatory feedback loop in resident synovial fibroblasts, who are orchestrating the inflammatory response in chronic arthritis. MiR-146a restricts their activation, thereby preventing excessive tissue damage during arthritis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Etanercept blocks inflammatory responses orchestrated by TNF-α to promote transplanted cell engraftment and proliferation in rat liver

PubMed Central

Viswanathan, Preeti; Kapoor, Sorabh; Kumaran, Vinay; Joseph, Brigid; Gupta, Sanjeev

2014-01-01

Engraftment of transplanted cells is critical for liver-directed cell therapy but most transplanted cells are rapidly cleared from liver sinusoids by proinflammatory cytokines/chemokines/receptors after activation of neutrophils or Kupffer cells. To define whether TNF-α served roles in cell-transplantation-induced hepatic inflammation, we used TNF-α antagonist, etanercept, for studies in syngeneic rat hepatocyte transplantation systems. After cell transplantation, multiple cytokines/chemokines/receptors were overexpressed, whereas etanercept prior to cell transplantation essentially normalized these responses. Moreover, ETN downregulated cell transplantation-induced intrahepatic release of secretory cytokines, such as high mobility group box 1. These effects of etanercept decreased cell transplantation-induced activation of neutrophils but not of Kupffer cells. Transplanted cell engraftment improved by several-fold in etanercept-treated animals. These gains in cell engraftment were repeatedly realized after pretreatment of animals with etanercept before multiple cell transplantation sessions. Transplanted cell numbers did not change over time indicating absence of cell proliferation after etanercept alone. By contrast, in animals preconditioned with retrorsine and partial hepatectomy, cell transplantation after etanercept pretreatment significantly accelerated liver repopulation compared with control rats. We concluded that TNF-α played a major role in orchestrating cell transplantation-induced inflammation through regulation of multiple cytokines/chemokines/receptor expression. As TNF-α antagonism by etanercept decreased transplanted cell clearance, improved cell engraftment and accelerated liver repopulation, this pharmacological approach to control hepatic inflammation will help optimize clinical strategies for liver cell therapy. PMID:24844924

A study of right shoulder injury in collegiate and professional orchestral cellists: an investigation using questionnaires and physical assessment.

PubMed

Rickert, Dale; Barrett, Margaret; Halaki, Mark; Driscoll, Tim; Ackermann, Bronwen

2012-06-01

Cellists sustain high levels of playing-related injury and are particularly susceptible to right shoulder pain, yet no studies have attempted to propose a mechanism for disease or establish possible causal factors. The aim of this study was to investigate shoulder injury levels and causes in two populations: professional orchestral cellists and college-level student cellists. A questionnaire and physical testing protocol was applied to both groups of participants, eliciting information on lifestyle, playing habits, and self-reported injury rates as well as physical data on shoulder strength, range of motion, and signs of injury. Right shoulder injuries are common among both student (20%) and professional (42%) cellists and seem to be associated with measures indicating potential lack of strength in the scapular stabilisers as well as potential degenerative changes in the rotator cuff. Significant differences were found in the lifestyle and playing habits of the two groups. There were increased signs of pain and stiffness in the professionals and evidence of decreased muscular support in the students. Male cellists showed less scapular stability; female cellists, however, generally had higher levels of pain. These results indicate that injuries at the shoulder, potentially involving impingement-type pathologies, are a common cause of pain in cellists. Based on this study, future research for cello players could focus on targeted interventions, such as exercises for the scapular stabilisers and muscles of the rotator cuff.

Patterns of gene expression reveal a temporally orchestrated wound healing response in the injured spinal cord.

PubMed

Velardo, Margaret J; Burger, Corinna; Williams, Philip R; Baker, Henry V; López, M Cecilia; Mareci, Thomas H; White, Todd E; Muzyczka, Nicholas; Reier, Paul J

2004-09-29

Spinal cord injury (SCI) induces a progressive pathophysiology affecting cell survival and neurological integrity via complex and evolving molecular cascades whose interrelationships are not fully understood. The present experiments were designed to: (1) determine potential functional interactions within transcriptional expression profiles obtained after a clinically relevant SCI and (2) test the consistency of transcript expression after SCI in two genetically and immunologically diverse rat strains characterized by differences in T cell competence and associated inflammatory responses. By interrogating Affymetrix U34A rat genome GeneChip microarrays, we defined the transcriptional expression patterns in midcervical contusion lesion sites between 1 and 90 d postinjury of athymic nude (AN) and Sprague Dawley (SD) strains. Stringent statistical analyses detected significant changes in 3638 probe sets, with 80 genes differing between the AN and SD groups. Subsequent detailed functional categorization of these transcripts unveiled an overall tissue remodeling response that was common to both strains. The functionally organized gene profiles were temporally distinct and correlated with repair indices observed microscopically and by magnetic resonance microimaging. Our molecular and anatomical observations have identified a novel, longitudinal perspective of the post-SCI response, namely, that of a highly orchestrated tissue repair and remodeling repertoire with a prominent cutaneous wound healing signature that is conserved between two widely differing rat strains. These results have significant bearing on the continuing development of cellular and pharmacological therapeutics directed at tissue rescue and neuronal regeneration in the injured spinal cord.

Förster resonance energy transfer as a tool to study photoreceptor biology

PubMed Central

Hovan, Stephanie C.; Howell, Scott; Park, Paul S.-H.

2010-01-01

Vision is initiated in photoreceptor cells of the retina by a set of biochemical events called phototransduction. These events occur via coordinated dynamic processes that include changes in secondary messenger concentrations, conformational changes and post-translational modifications of signaling proteins, and protein-protein interactions between signaling partners. A complete description of the orchestration of these dynamic processes is still unavailable. Described in this work is the first step in the development of tools combining fluorescent protein technology, Förster resonance energy transfer (FRET), and transgenic animals that have the potential to reveal important molecular insights about the dynamic processes occurring in photoreceptor cells. We characterize the fluorescent proteins SCFP3A and SYFP2 for use as a donor-acceptor pair in FRET assays, which will facilitate the visualization of dynamic processes in living cells. We also demonstrate the targeted expression of these fluorescent proteins to the rod photoreceptor cells of Xenopus laevis, and describe a general method for detecting FRET in these cells. The general approaches described here can address numerous types of questions related to phototransduction and photoreceptor biology by providing a platform to visualize dynamic processes in molecular detail within a native context. PMID:21198205

Enriching the Web Processing Service

NASA Astrophysics Data System (ADS)

Wosniok, Christoph; Bensmann, Felix; Wössner, Roman; Kohlus, Jörn; Roosmann, Rainer; Heidmann, Carsten; Lehfeldt, Rainer

2014-05-01

The OGC Web Processing Service (WPS) provides a standard for implementing geospatial processes in service-oriented networks. In its current version 1.0.0 it allocates the operations GetCapabilities, DescribeProcess and Execute, which can be used to offer custom processes based on single or multiple sub-processes. A large range of ready to use fine granular, fundamental geospatial processes have been developed by the GIS-community in the past. However, modern use cases or whole workflow processes demand specifications of lifecycle management and service orchestration. Orchestrating smaller sub-processes is a task towards interoperability; a comprehensive documentation by using appropriate metadata is also required. Though different approaches were tested in the past, developing complex WPS applications still requires programming skills, knowledge about software libraries in use and a lot of effort for integration. Our toolset RichWPS aims at providing a better overall experience by setting up two major components. The RichWPS ModelBuilder enables the graphics-aided design of workflow processes based on existing local and distributed processes and geospatial services. Once tested by the RichWPS Server, a composition can be deployed for production use on the RichWPS Server. The ModelBuilder obtains necessary processes and services from a directory service, the RichWPS semantic proxy. It manages the lifecycle and is able to visualize results and debugging-information. One aim will be to generate reproducible results; the workflow should be documented by metadata that can be integrated in Spatial Data Infrastructures. The RichWPS Server provides a set of interfaces to the ModelBuilder for, among others, testing composed workflow sequences, estimating their performance and to publish them as common processes. Therefore the server is oriented towards the upcoming WPS 2.0 standard and its ability to transactionally deploy and undeploy processes making use of a WPS-T interface. In order to deal with the results of these processing workflows, a server side extension enables the RichWPS Server and its clients to use WPS presentation directives (WPS-PD), a content related enhancement for the standardized WPS schema. We identified essential requirements of the components of our toolset by applying two use cases. The first enables the simplified comparison of modeled and measured data, a common task in hydro-engineering to validate the accuracy of a model. An implementation of the workflow includes reading, harmonizing and comparing two datasets in NetCDF-format. 2D Water level data from the German Bight can be chosen, presented and evaluated in a web client with interactive plots. The second use case is motivated by the Marine Strategy Directive (MSD) of the EU, which demands monitoring, action plans and at least an evaluation of the ecological situation in marine environment. Information technics adapted to those of INSPIRE should be used. One of the parameters monitored and evaluated for MSD is the expansion and quality of seagrass fields. With the view towards other evaluation parameters we decompose the complex process of evaluation of seagrass in reusable process steps and implement those packages as configurable WPS.

Cleft Lip and Palate Surgery

MedlinePlus

... The experts in face, mouth and jaw surgery. Cleft Lip / Palate and Craniofacial Surgery This type of surgery is ... the carefully orchestrated, multiple-stage correctional program for cleft lip and palate patients. The goal is to help restore the ...

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...

Teaching Children How to Discuss What They Read.

ERIC Educational Resources Information Center

Perez, Samuel A.; Strickland, Eric V.

1986-01-01

Explains that teachers must understand that discussion is not a simple collection of listening and speaking skills but a dynamic event that requires children to orchestrate a number of language skills. Offers suggestions for improving discussions. (FL)

Constituency Input into Budget Management.

ERIC Educational Resources Information Center

Miller, Norman E.

1995-01-01

Presents techniques for ensuring constituency involvement in district- and site-level budget management. Outlines four models for securing constituent input and focuses on strategies to orchestrate the more complex model for staff and community participation. Two figures are included. (LMI)

Design of Control Plane Architecture Based on Cloud Platform and Experimental Network Demonstration for Multi-domain SDON

NASA Astrophysics Data System (ADS)

Li, Ming; Yin, Hongxi; Xing, Fangyuan; Wang, Jingchao; Wang, Honghuan

2016-02-01

With the features of network virtualization and resource programming, Software Defined Optical Network (SDON) is considered as the future development trend of optical network, provisioning a more flexible, efficient and open network function, supporting intraconnection and interconnection of data centers. Meanwhile cloud platform can provide powerful computing, storage and management capabilities. In this paper, with the coordination of SDON and cloud platform, a multi-domain SDON architecture based on cloud control plane has been proposed, which is composed of data centers with database (DB), path computation element (PCE), SDON controller and orchestrator. In addition, the structure of the multidomain SDON orchestrator and OpenFlow-enabled optical node are proposed to realize the combination of centralized and distributed effective management and control platform. Finally, the functional verification and demonstration are performed through our optical experiment network.

Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut.

PubMed

Howitt, Michael R; Lavoie, Sydney; Michaud, Monia; Blum, Arthur M; Tran, Sara V; Weinstock, Joel V; Gallini, Carey Ann; Redding, Kevin; Margolskee, Robert F; Osborne, Lisa C; Artis, David; Garrett, Wendy S

2016-03-18

The intestinal epithelium forms an essential barrier between a host and its microbiota. Protozoa and helminths are members of the gut microbiota of mammals, including humans, yet the many ways that gut epithelial cells orchestrate responses to these eukaryotes remain unclear. Here we show that tuft cells, which are taste-chemosensory epithelial cells, accumulate during parasite colonization and infection. Disruption of chemosensory signaling through the loss of TRMP5 abrogates the expansion of tuft cells, goblet cells, eosinophils, and type 2 innate lymphoid cells during parasite colonization. Tuft cells are the primary source of the parasite-induced cytokine interleukin-25, which indirectly induces tuft cell expansion by promoting interleukin-13 production by innate lymphoid cells. Our results identify intestinal tuft cells as critical sentinels in the gut epithelium that promote type 2 immunity in response to intestinal parasites. Copyright © 2016, American Association for the Advancement of Science.

Multimodal Teaching Analytics: Automated Extraction of Orchestration Graphs from Wearable Sensor Data.

PubMed

Prieto, Luis P; Sharma, Kshitij; Kidzinski, Łukasz; Rodríguez-Triana, María Jesús; Dillenbourg, Pierre

2018-04-01

The pedagogical modelling of everyday classroom practice is an interesting kind of evidence, both for educational research and teachers' own professional development. This paper explores the usage of wearable sensors and machine learning techniques to automatically extract orchestration graphs (teaching activities and their social plane over time), on a dataset of 12 classroom sessions enacted by two different teachers in different classroom settings. The dataset included mobile eye-tracking as well as audiovisual and accelerometry data from sensors worn by the teacher. We evaluated both time-independent and time-aware models, achieving median F1 scores of about 0.7-0.8 on leave-one-session-out k-fold cross-validation. Although these results show the feasibility of this approach, they also highlight the need for larger datasets, recorded in a wider variety of classroom settings, to provide automated tagging of classroom practice that can be used in everyday practice across multiple teachers.

The high-affinity phosphodiesterase PdeH regulates development and aflatoxin biosynthesis in Aspergillus flavus.

PubMed

Yang, Kunlong; Liu, Yinghang; Liang, Linlin; Li, Zhenguo; Qin, Qiuping; Nie, Xinyi; Wang, Shihua

2017-04-01

Cyclic AMP signaling controls a range of physiological processes in response to extracellular stimuli in organisms. Among the signaling cascades, cAMP, as a second messenger, is orchestrated by adenylate cyclase (biosynthesis) and cAMP phosphodiesterases (PDEs) (hydrolysis). In this study, we investigated the function of the high-affinity (PdeH) and low-affinity (PdeL) cAMP phosphodiesterase from the carcinogenic aflatoxin producing fungus Aspergillus flavus, and found that instead of PdeL, inactivation of PdeH exhibited a reduction in conidiation and sclerotia formation. However, the ΔpdeL/ΔpdeH mutant exhibited an enhanced phenotype defects, a similar phenotype defects to wild-type strain treated with exogenous cAMP. The activation of PKA activity was inhibited in the ΔpdeH or ΔpdeL/ΔpdeH mutant, both of whom exhibited increasing AF production. Further analysis by qRT-PCR revealed that pdeH had a high transcriptional level compared to pdeL in wild-type strain, and affected pdeL transcription. Green fluorescent protein tagging at the C-terminus of PDEs showed that PdeH-GFP is broadly compartmentalized in the cytosol, while PdeL-GFP localized mainly to the nucleus. Overall, our results indicated that PdeH plays a major role, but has overlapping function with PdeL, in vegetative growth, development and AF biosynthesis in A. flavus. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Monitoring Interactions and Dynamics of Endogenous Beta-catenin With Intracellular Nanobodies in Living Cells*

PubMed Central

Traenkle, Bjoern; Emele, Felix; Anton, Roman; Poetz, Oliver; Haeussler, Ragna S.; Maier, Julia; Kaiser, Philipp D.; Scholz, Armin M.; Nueske, Stefan; Buchfellner, Andrea; Romer, Tina; Rothbauer, Ulrich

2015-01-01

β-catenin is the key component of the canonical Wnt pathway and plays a crucial role in a multitude of developmental and homeostatic processes. The different tasks of β-catenin are orchestrated by its subcellular localization and participation in multiprotein complexes. To gain a better understanding of β-catenin's role in living cells we have generated a new set of single domain antibodies, referred to as nanobodies, derived from heavy chain antibodies of camelids. We selected nanobodies recognizing the N-terminal, core or C-terminal domain of β-catenin and applied these new high-affinity binders as capture molecules in sandwich immunoassays and co-immunoprecipitations of endogenous β-catenin complexes. In addition, we engineered intracellularly functional anti-β-catenin chromobodies by combining the binding moieties of the nanobodies with fluorescent proteins. For the first time, we were able to visualize the subcellular localization and nuclear translocation of endogenous β-catenin in living cells using these chromobodies. Moreover, the chromobody signal allowed us to trace the accumulation of diffusible, hypo-phosphorylated β-catenin in response to compound treatment in real time using High Content Imaging. The anti-β-catenin nanobodies and chromobodies characterized in this study are versatile tools that enable a novel and unique approach to monitor the dynamics of subcellular β-catenin in biochemical and cell biological assays. PMID:25595278

Diel-scale temporal dynamics recorded for bacterial groups in Namib Desert soil

PubMed Central

Gunnigle, Eoin; Frossard, Aline; Ramond, Jean-Baptiste; Guerrero, Leandro; Seely, Mary; Cowan, Don A.

2017-01-01

Microbes in hot desert soil partake in core ecosystem processes e.g., biogeochemical cycling of carbon. Nevertheless, there is still a fundamental lack of insights regarding short-term (i.e., over a 24-hour [diel] cycle) microbial responses to highly fluctuating microenvironmental parameters like temperature and humidity. To address this, we employed T-RFLP fingerprinting and 454 pyrosequencing of 16S rRNA-derived cDNA to characterize potentially active bacteria in Namib Desert soil over multiple diel cycles. Strikingly, we found that significant shifts in active bacterial groups could occur over a single 24-hour period. For instance, members of the predominant Actinobacteria phyla exhibited a significant reduction in relative activity from morning to night, whereas many Proteobacterial groups displayed an opposite trend. Contrary to our leading hypothesis, environmental parameters could only account for 10.5% of the recorded total variation. Potential biotic associations shown through co-occurrence networks indicated that non-random inter- and intra-phyla associations were ‘time-of-day-dependent’ which may constitute a key feature of this system. Notably, many cyanobacterial groups were positioned outside and/or between highly interconnected bacterial associations (modules); possibly acting as inter-module ‘hubs’ orchestrating interactions between important functional consortia. Overall, these results provide empirical evidence that bacterial communities in hot desert soils exhibit complex and diel-dependent inter-community associations. PMID:28071697

Diel-scale temporal dynamics recorded for bacterial groups in Namib Desert soil

NASA Astrophysics Data System (ADS)

Gunnigle, Eoin; Frossard, Aline; Ramond, Jean-Baptiste; Guerrero, Leandro; Seely, Mary; Cowan, Don A.

2017-01-01

Microbes in hot desert soil partake in core ecosystem processes e.g., biogeochemical cycling of carbon. Nevertheless, there is still a fundamental lack of insights regarding short-term (i.e., over a 24-hour [diel] cycle) microbial responses to highly fluctuating microenvironmental parameters like temperature and humidity. To address this, we employed T-RFLP fingerprinting and 454 pyrosequencing of 16S rRNA-derived cDNA to characterize potentially active bacteria in Namib Desert soil over multiple diel cycles. Strikingly, we found that significant shifts in active bacterial groups could occur over a single 24-hour period. For instance, members of the predominant Actinobacteria phyla exhibited a significant reduction in relative activity from morning to night, whereas many Proteobacterial groups displayed an opposite trend. Contrary to our leading hypothesis, environmental parameters could only account for 10.5% of the recorded total variation. Potential biotic associations shown through co-occurrence networks indicated that non-random inter- and intra-phyla associations were ‘time-of-day-dependent’ which may constitute a key feature of this system. Notably, many cyanobacterial groups were positioned outside and/or between highly interconnected bacterial associations (modules); possibly acting as inter-module ‘hubs’ orchestrating interactions between important functional consortia. Overall, these results provide empirical evidence that bacterial communities in hot desert soils exhibit complex and diel-dependent inter-community associations.

Multiple selective events at the PRDM16 functional pathway shaped adaptation of western European populations to different climate conditions.

PubMed

Quagliarello, Andrea; De Fanti, Sara; Giuliani, Cristina; Abondio, Paolo; Serventi, Patrizia; Sarno, Stefania; Sazzini, Marco; Luiselli, Donata

2017-12-30

Several studies highlighted the role of climate in shaping many human evolutionary processes. This occurred even in relatively recent times, having affected various human phenotypic traits, among which metabolic processes that orchestrate absorption and accumulation of substances to maintain energy homeostasis, that is critical for the survival of individuals in high energy-expenditure environments. To date, most researches have focalized on detection of climatic influence on SNPs' frequency in populations exposed to extreme environmental conditions or by comparing variation patterns between populations from different continents. In this study, we instead explored the genetic background of distinct western European human groups at loci involved in nutritional and thermoregulation processes, to test whether patterns of differential local adaptation to environmental conditions could be appreciated also at a lower geographical scale. Taking advantage from the 1000 Genomes Project data, genetic information for 21 genes involved in nutritional and thermoregulation processes was analysed for three western European populations. The applied Anthropological Genetics methods pointed to appreciable differentiation between the examined groups especially for the PRDM16 gene. Moreover, several neutrality tests suggested that balancing selection has acted on different regions of the gene in people from Great Britain, as well as that more recent positive selection could have also targeted some PRDM16 SNPs in Finn and Italian populations. These series of adaptive footprints are plausibly related to climate variability in both ancient and relatively recent times. Since this locus is involved in thermoregulation mechanisms and adipogenesis, local adaptations mediated by a pathway related to the brown adipose tissue activity could have evolved in response to changing cold temperature exposures of such populations.

Hyperosmotic nanoemulsions: Development and application of a new antimicrobial treatment for wound care

NASA Astrophysics Data System (ADS)

Connell, Sean

Wound healing is the intricate process that restores function to damaged skin. The process consists of the inflammatory, proliferative and remodeling phases that orchestrate dynamic cellular responses to regenerate the cutaneous barrier. However, microbial contamination of the wound site stimulates a deleterious inflammatory response with the production of endotoxins, exotoxins and proteases that result in secondary injury. The end result is delayed healing, protracted debilitation and increased health care costs. Controlling contamination is critical for proper wound management and reduced burden on the healthcare system. Based on this concern, we developed and applied a new antimicrobial therapeutic that relies on hyperosmotic nanoemulsions (HNE). The biomechanical process consists of a high-energy nanoemulsion component that permeates the protective microbial membrane and a (ii) nonionic hyperosmoticum that facilitates intracellular water extraction to critically dehydrate the pathogen. HNE was shown to be effective against a multitude of pathogens including bacteria, antibiotic-resistant variants, fungi and viruses. Reported non-clinical studies demonstrate that the membrane disrupting nanoemulsion and hyperosmotic component act synergistically to enhance microbicidal activity. Further, results illustrate that pathogen inactivation was rapid as determined by ion and macromolecule leakage assays. Application of HNE in a pre-clinical animal model of wound healing demonstrated the treatment actively promoted healing to reduce treatment times. HNE mitigated wound infection to reduce the inflammatory response and mechanically debrided the wound to facilitate wound closure. Recent work further enhanced the stability of the nanoemulsion component with the addition of surfactant stabilizers using a low-energy spontaneous emulsification process. The refined nanoemulsion composition was stable against physical stressors and long-term storage without disrupting the intrinsic antimicrobial attributes. The reported findings have key implications for the development and application of a new antimicrobial therapeutic platform for wound management.

32 CFR 159.6 - Procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... as country information and cultural training, and guidance on working with host country nationals and... geographic Combatant Commander shall develop and publish guidance and procedures for PSCs and PSC personnel....49, “Orchestrating, Synchronizing, and Integrating Program Management of Contingency Acquisition...

32 CFR 159.6 - Procedures.

Code of Federal Regulations, 2012 CFR

2012-07-01

... as country information and cultural training, and guidance on working with host country nationals and... geographic Combatant Commander shall develop and publish guidance and procedures for PSCs and PSC personnel....49, “Orchestrating, Synchronizing, and Integrating Program Management of Contingency Acquisition...

32 CFR 159.6 - Procedures.

Code of Federal Regulations, 2013 CFR

2013-07-01

... as country information and cultural training, and guidance on working with host country nationals and... geographic Combatant Commander shall develop and publish guidance and procedures for PSCs and PSC personnel....49, “Orchestrating, Synchronizing, and Integrating Program Management of Contingency Acquisition...

32 CFR 159.6 - Procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

....49, “Orchestrating, Synchronizing, and Integrating Program Management of Contingency Acquisition... increased risk or planned or ongoing military operations, including how PSC personnel will be rapidly... 13 shall provide the framework for the development of guidance and procedures without regard to the...

Monitoring Replication Protein A (RPA) dynamics in homologous recombination through site-specific incorporation of non-canonical amino acids

PubMed Central

Pokhrel, Nilisha; Origanti, Sofia; Davenport, Eric Parker; Gandhi, Disha; Kaniecki, Kyle; Mehl, Ryan A.; Greene, Eric C.; Dockendorff, Chris

2017-01-01

Abstract An essential coordinator of all DNA metabolic processes is Replication Protein A (RPA). RPA orchestrates these processes by binding to single-stranded DNA (ssDNA) and interacting with several other DNA binding proteins. Determining the real-time kinetics of single players such as RPA in the presence of multiple DNA processors to better understand the associated mechanistic events is technically challenging. To overcome this hurdle, we utilized non-canonical amino acids and bio-orthogonal chemistry to site-specifically incorporate a chemical fluorophore onto a single subunit of heterotrimeric RPA. Upon binding to ssDNA, this fluorescent RPA (RPAf) generates a quantifiable change in fluorescence, thus serving as a reporter of its dynamics on DNA in the presence of multiple other DNA binding proteins. Using RPAf, we describe the kinetics of facilitated self-exchange and exchange by Rad51 and mediator proteins during various stages in homologous recombination. RPAf is widely applicable to investigate its mechanism of action in processes such as DNA replication, repair and telomere maintenance. PMID:28934470

SMN control of RNP assembly: from post-transcriptional gene regulation to motor neuron disease

PubMed Central

Li, Darrick K.; Tisdale, Sarah; Lotti, Francesco; Pellizzoni, Livio

2014-01-01

At the post-transcriptional level, expression of protein-coding genes is controlled by a series of RNA regulatory events including nuclear processing of primary transcripts, transport of mature mRNAs to specific cellular compartments, translation and ultimately, turnover. These processes are orchestrated through the dynamic association of mRNAs with RNA binding proteins and ribonucleoprotein (RNP) complexes. Accurate formation of RNPs in vivo is fundamentally important to cellular development and function, and its impairment often leads to human disease. The survival motor neuron (SMN) protein is key to this biological paradigm: SMN is essential for the biogenesis of various RNPs that function in mRNA processing, and genetic mutations leading to SMN deficiency cause the neurodegenerative disease spinal muscular atrophy. Here we review the expanding role of SMN in the regulation of gene expression through its multiple functions in RNP assembly. We discuss advances in our understanding of SMN activity as a chaperone of RNPs and how disruption of SMN-dependent RNA pathways can cause motor neuron disease. PMID:24769255

Herpesvirus gB: A Finely Tuned Fusion Machine

PubMed Central

Cooper, Rebecca S.; Heldwein, Ekaterina E.

2015-01-01

Enveloped viruses employ a class of proteins known as fusogens to orchestrate the merger of their surrounding envelope and a target cell membrane. Most fusogens accomplish this task alone, by binding cellular receptors and subsequently catalyzing the membrane fusion process. Surprisingly, in herpesviruses, these functions are distributed among multiple proteins: the conserved fusogen gB, the conserved gH/gL heterodimer of poorly defined function, and various non-conserved receptor-binding proteins. We summarize what is currently known about gB from two closely related herpesviruses, HSV-1 and HSV-2, with emphasis on the structure of the largely uncharted membrane interacting regions of this fusogen. We propose that the unusual mechanism of herpesvirus fusion could be linked to the unique architecture of gB. PMID:26690469

Recent Insights into the Regulation of the Growth Plate

PubMed Central

Lui, Julian C.; Nilsson, Ola; Baron, Jeffrey

2014-01-01

For most bones, elongation is driven primarily by chondrogenesis at the growth plates. This process results from chondrocyte proliferation, hypertrophy, and extracellular matrix secretion and is carefully orchestrated by complex networks of local paracrine factors and modulated by endocrine factors. We review here recent advances in the understanding of growth plate physiology. These advances include new approaches to study expression patterns of large numbers of genes in the growth plate, using microdissection followed by microarray. This approach has been combined with genome-wide association studies to provide insights into the regulation of the human growth plate. We also review recent studies elucidating the roles of bone morphogenetic proteins, fibroblast growth factors, C-type natriuretic peptide, and suppressor of cytokine signaling in the local regulation of growth plate chondrogenesis and longitudinal bone growth. PMID:24740736

Targeting oncogenic Myc as a strategy for cancer treatment.

PubMed

Chen, Hui; Liu, Hudan; Qing, Guoliang

2018-01-01

The MYC family oncogene is deregulated in >50% of human cancers, and this deregulation is frequently associated with poor prognosis and unfavorable patient survival. Myc has a central role in almost every aspect of the oncogenic process, orchestrating proliferation, apoptosis, differentiation, and metabolism. Although Myc inhibition would be a powerful approach for the treatment of many types of cancers, direct targeting of Myc has been a challenge for decades owing to its "undruggable" protein structure. Hence, alternatives to Myc blockade have been widely explored to achieve desirable anti-tumor effects, including Myc/Max complex disruption, MYC transcription and/or translation inhibition, and Myc destabilization as well as the synthetic lethality associated with Myc overexpression. In this review, we summarize the latest advances in targeting oncogenic Myc, particularly for cancer therapeutic purposes.

Prototype of Kepler Processing Workflows For Microscopy And Neuroinformatics

PubMed Central

Astakhov, V.; Bandrowski, A.; Gupta, A.; Kulungowski, A.W.; Grethe, J.S.; Bouwer, J.; Molina, T.; Rowley, V.; Penticoff, S.; Terada, M.; Wong, W.; Hakozaki, H.; Kwon, O.; Martone, M.E.; Ellisman, M.

2016-01-01

We report on progress of employing the Kepler workflow engine to prototype “end-to-end” application integration workflows that concern data coming from microscopes deployed at the National Center for Microscopy Imaging Research (NCMIR). This system is built upon the mature code base of the Cell Centered Database (CCDB) and integrated rule-oriented data system (IRODS) for distributed storage. It provides integration with external projects such as the Whole Brain Catalog (WBC) and Neuroscience Information Framework (NIF), which benefit from NCMIR data. We also report on specific workflows which spawn from main workflows and perform data fusion and orchestration of Web services specific for the NIF project. This “Brain data flow” presents a user with categorized information about sources that have information on various brain regions. PMID:28479932

Sirtuins of parasitic protozoa: In search of function(s)

PubMed Central

Religa, Agnieszka A.; Waters, Andrew P.

2012-01-01

The SIR2 family of NAD+-dependent protein deacetylases, collectively called sirtuins, has been of central interest due to their proposed roles in life-span regulation and ageing. Sirtuins are one group of environment sensors of a cell interpreting external information and orchestrating internal responses at the sub-cellular level, through participation in gene regulation mechanisms. Remarkably conserved across all kingdoms of life SIR2 proteins in several protozoan parasites appear to have both conserved and intriguing unique functions. This review summarises our current knowledge of the members of the sirtuin families in Apicomplexa, including Plasmodium, and other protozoan parasites such as Trypanosoma and Leishmania. The wide diversity of processes regulated by SIR2 proteins makes them targets worthy of exploitation in anti-parasitic therapies. PMID:22906508

Moving and Learning in Every Way. Profiles/Elizabeth O'Brien.

ERIC Educational Resources Information Center

Rife, Frank

1982-01-01

A physical education teacher's approach to orchestrating individual and group learning is described. Cognitive and affective learning are stressed in addition to physical skill development. Creative use of learning resources--milk cartons, "direction boxes," and newspapers--is illustrated. (PP)

Quantification of bovine oxylipids during intramammary Streptococcus uberis infection

USDA-ARS?s Scientific Manuscript database

Streptococcus uberis mastitis results in severe mammary tissue damage in dairy cows due to uncontrolled inflammation. Oxylipids are potent lipid mediators that orchestrate pathogen-induced inflammatory responses, however, changes in oxylipid biosynthesis during S. uberis mastitis are unknown. Thus, ...

Demonstrating Distributed Resource Communications at NREL - Video Text

Science.gov Websites

video. Kevin Lynn, DOE Director of Grid Modernization: This is a whole new way of thinking about the way orchestration and coordination is more of what's coming and utilities are thinking more and more about what

Taking Care of Your Voice

MedlinePlus

... open so that you can breathe. When it's time to speak, however, the brain orchestrates a series of events. The vocal folds snap together while ... Communication Disorders (NIDCD) supports research that includes laboratory ... other scientists design better treatments for conditions such as vocal fold ...

The role of genetics and antibodies in sepsis

PubMed Central

Giamarellos-Bourboulis, Evangelos J.

2016-01-01

During the course of sepsis when immunosuppression predominates, the concentrations of circulating immunoglobulins (IGs) are decreased and this is associated with adverse outcomes. The production of IGs as response to invasive bacterial pathogens takes place through a complex pathway starting from the recognition of the antigen (Ag) by innate immune cells that process and present Ags to T cells. The orchestration of T-helper (Th) lymphocyte responses directs specific B cells and ends with the production of IGs by plasma cells. All molecules implicated in this process are encoded by genes bearing single nucleotide polymorphisms (SNPs). Meta-analysis of case-control studies have shown that the carriage of minor frequency SNPs of CD14, TLR2 and TNF is associated with increased sepsis risk. The ambiguity of results of clinical trials studying the clinical efficacy of exogenous IG administration in sepsis suggests that efficacy of treatment should be considered after adjustment for SNPs of all implicated genes in the pathway of IG production. PMID:27713886

The role of genetics and antibodies in sepsis.

PubMed

Giamarellos-Bourboulis, Evangelos J; Opal, Steven M

2016-09-01

During the course of sepsis when immunosuppression predominates, the concentrations of circulating immunoglobulins (IGs) are decreased and this is associated with adverse outcomes. The production of IGs as response to invasive bacterial pathogens takes place through a complex pathway starting from the recognition of the antigen (Ag) by innate immune cells that process and present Ags to T cells. The orchestration of T-helper (Th) lymphocyte responses directs specific B cells and ends with the production of IGs by plasma cells. All molecules implicated in this process are encoded by genes bearing single nucleotide polymorphisms (SNPs). Meta-analysis of case-control studies have shown that the carriage of minor frequency SNPs of CD14 , TLR2 and TNF is associated with increased sepsis risk. The ambiguity of results of clinical trials studying the clinical efficacy of exogenous IG administration in sepsis suggests that efficacy of treatment should be considered after adjustment for SNPs of all implicated genes in the pathway of IG production.

Ubiquitination in Periodontal Disease: A Review.

PubMed

Tsuchida, Sachio; Satoh, Mamoru; Takiwaki, Masaki; Nomura, Fumio

2017-07-10

Periodontal disease (periodontitis) is a chronic inflammatory condition initiated by microbial infection that leads to gingival tissue destruction and alveolar bone resorption. The periodontal tissue's response to dental plaque is characterized by the accumulation of polymorphonuclear leukocytes, macrophages, and lymphocytes, all of which release inflammatory mediators and cytokines to orchestrate the immunopathogenesis of periodontal disease. Ubiquitination is achieved by a mechanism that involves a number of factors, including an ubiquitin-activating enzyme, ubiquitin-conjugating enzyme, and ubiquitin-protein ligase. Ubiquitination is a post-translational modification restricted to eukaryotes that are involved in essential host processes. The ubiquitin system has been implicated in the immune response, development, and programmed cell death. Increasing numbers of recent reports have provided evidence that many approaches are delivering promising reports for discovering the relationship between ubiquitination and periodontal disease. The scope of this review was to investigate recent progress in the discovery of ubiquitinated protein in diseased periodontium and to discuss the ubiquitination process in periodontal diseases.

Ubiquitination in Periodontal Disease: A Review

PubMed Central

Tsuchida, Sachio; Satoh, Mamoru; Takiwaki, Masaki; Nomura, Fumio

2017-01-01

Periodontal disease (periodontitis) is a chronic inflammatory condition initiated by microbial infection that leads to gingival tissue destruction and alveolar bone resorption. The periodontal tissue’s response to dental plaque is characterized by the accumulation of polymorphonuclear leukocytes, macrophages, and lymphocytes, all of which release inflammatory mediators and cytokines to orchestrate the immunopathogenesis of periodontal disease. Ubiquitination is achieved by a mechanism that involves a number of factors, including an ubiquitin-activating enzyme, ubiquitin-conjugating enzyme, and ubiquitin–protein ligase. Ubiquitination is a post-translational modification restricted to eukaryotes that are involved in essential host processes. The ubiquitin system has been implicated in the immune response, development, and programmed cell death. Increasing numbers of recent reports have provided evidence that many approaches are delivering promising reports for discovering the relationship between ubiquitination and periodontal disease. The scope of this review was to investigate recent progress in the discovery of ubiquitinated protein in diseased periodontium and to discuss the ubiquitination process in periodontal diseases. PMID:28698506

Roles of the oviduct in mammalian fertilization

PubMed Central

Coy, P; García-Vázquez, FA; Visconti, PE; Avilés, M

2014-01-01

The oviduct or Fallopian tube is the anatomical region where every new life begins in mammalian species. After a long journey, the spermatozoa meet the oocyte in the specific site of the oviduct named ampulla, and fertilization takes place. The successful fertilization depends on several biological processes which occur in the oviduct some hours before this rendezvous and affect both gametes. Estrogen and progesterone, released from the ovary, orchestrate a series of changes by genomic- and non-genomic pathways in the oviductal epithelium affecting gene expression, proteome and secretion of its cells into the fluid bathing the oviductal lumen. In addition, new regulatory molecules are being discovered playing important roles in oviductal physiology and fertilization. The present review tries to describe these processes, building a comprehensive map of the physiology of the oviduct, to better understand the importance of this organ in reproduction. With this purpose, gamete transport, sperm and oocyte changes in the oviductal environment and other interactions between gametes and oviduct are discussed in light of recent publications in the field. PMID:23028122

The Glide/Gcm fate determinant controls initiation of collective cell migration by regulating Frazzled

PubMed Central

Gupta, Tripti; Kumar, Arun; Cattenoz, Pierre B.; VijayRaghavan, K; Giangrande, Angela

2016-01-01

Collective migration is a complex process that contributes to build precise tissue and organ architecture. Several molecules implicated in cell interactions also control collective migration, but their precise role and the finely tuned expression that orchestrates this complex developmental process are poorly understood. Here, we show that the timely and threshold expression of the Netrin receptor Frazzled triggers the initiation of glia migration in the developing Drosophila wing. Frazzled expression is induced by the transcription factor Glide/Gcm in a dose-dependent manner. Thus, the glial determinant also regulates the efficiency of collective migration. NetrinB but not NetrinA serves as a chemoattractant and Unc5 contributes as a repellant Netrin receptor for glia migration. Our model includes strict spatial localization of a ligand, a cell autonomously acting receptor and a fate determinant that act coordinately to direct glia toward their final destination. DOI: http://dx.doi.org/10.7554/eLife.15983.001 PMID:27740455

Brushes, cables, and anchors: recent insights into multiscale assembly and mechanics of cellular structural networks.

PubMed

Lele, Tanmay P; Kumar, Sanjay

2007-01-01

The remarkable ability of living cells to sense, process, and respond to mechanical stimuli in their environment depends on the rapid and efficient interconversion of mechanical and chemical energy at specific times and places within the cell. For example, application of force to cells leads to conformational changes in specific mechanosensitive molecules which then trigger cellular signaling cascades that may alter cellular structure, mechanics, and migration and profoundly influence gene expression. Similarly, the sensitivity of cells to mechanical stresses is governed by the composition, architecture, and mechanics of the cellular cytoskeleton and extracellular matrix (ECM), which are in turn driven by molecular-scale forces between the constituent biopolymers. Understanding how these mechanochemical systems coordinate over multiple length and time scales to produce orchestrated cell behaviors represents a fundamental challenge in cell biology. Here, we review recent advances in our understanding of these complex processes in three experimental systems: the assembly of axonal neurofilaments, generation of tensile forces by actomyosin stress fiber bundles, and mechanical control of adhesion assembly.

Identifying pathways affected by cancer mutations.

PubMed

Iengar, Prathima

2017-12-16

Mutations in 15 cancers, sourced from the COSMIC Whole Genomes database, and 297 human pathways, arranged into pathway groups based on the processes they orchestrate, and sourced from the KEGG pathway database, have together been used to identify pathways affected by cancer mutations. Genes studied in ≥15, and mutated in ≥10 samples of a cancer have been considered recurrently mutated, and pathways with recurrently mutated genes have been considered affected in the cancer. Novel doughnut plots have been presented which enable visualization of the extent to which pathways and genes, in each pathway group, are targeted, in each cancer. The 'organismal systems' pathway group (including organism-level pathways; e.g., nervous system) is the most targeted, more than even the well-recognized signal transduction, cell-cycle and apoptosis, and DNA repair pathway groups. The important, yet poorly-recognized, role played by the group merits attention. Pathways affected in ≥7 cancers yielded insights into processes affected. Copyright © 2017 Elsevier Inc. All rights reserved.

Timing is everything: Fine-tuned molecular machines orchestrate paramyxovirus entry.

PubMed

Bose, Sayantan; Jardetzky, Theodore S; Lamb, Robert A

2015-05-01

The Paramyxoviridae include some of the great and ubiquitous disease-causing viruses of humans and animals. In most paramyxoviruses, two viral membrane glycoproteins, fusion protein (F) and receptor binding protein (HN, H or G) mediate a concerted process of recognition of host cell surface molecules followed by fusion of viral and cellular membranes, resulting in viral nucleocapsid entry into the cytoplasm. The interactions between the F and HN, H or G viral glycoproteins and host molecules are critical in determining host range, virulence and spread of these viruses. Recently, atomic structures, together with biochemical and biophysical studies, have provided major insights into how these two viral glycoproteins successfully interact with host receptors on cellular membranes and initiate the membrane fusion process to gain entry into cells. These studies highlight the conserved core mechanisms of paramyxovirus entry that provide the fundamental basis for rational anti-viral drug design and vaccine development. Copyright © 2015 Elsevier Inc. All rights reserved.

HELIOGate, a Portal for the Heliophysics Community

NASA Astrophysics Data System (ADS)

Pierantoni; Gabriele; Carley, Eoin

2014-10-01

Heliophysics is the branch of physics that investigates the interactions between the Sun and the other bodies of the solar system. Heliophysicists rely on data collected from numerous sources scattered across the Solar System. The data collected from these sources is processed to extract metadata and the metadata extracted in this fashion is then used to build indexes of features and events called catalogues. Heliophysicists also develop conceptual and mathematical models of the phenomena and the environment of the Solar System. More specifically, they investigate the physical characteristics of the phenomena and they simulate how they propagate throughout the Solar System with mathematical and physical abstractions called propagation models. HELIOGate aims at addressing the need to combine and orchestrate existing web services in a flexible and easily configurable fashion to tackle different scientific questions. HELIOGate also offers a tool capable of connecting to size! able computation and storage infrastructures to execute data processing codes that are needed to calibrate raw data and to extract metadata.

Cellular v-ATPase is required for virion assembly compartment formation in human cytomegalovirus infection

PubMed Central

Pavelin, Jonathan; McCormick, Dominique; Chiweshe, Stephen; Ramachandran, Saranya; Lin, Yao-Tang

2017-01-01

Successful generation of virions from infected cells is a complex process requiring orchestrated regulation of host and viral genes. Cells infected with human cytomegalovirus (HCMV) undergo a dramatic reorganization of membrane organelles resulting in the formation of the virion assembly compartment, a process that is not fully understood. Here we show that acidification of vacuoles by the cellular v-ATPase is a crucial step in the formation of the virion assembly compartment and disruption of acidification results in mis-localization of virion components and a profound reduction in infectious virus levels. In addition, knockdown of ATP6V0C blocks the increase in nuclear size, normally associated with HCMV infection. Inhibition of the v-ATPase does not affect intracellular levels of viral DNA synthesis or gene expression, consistent with a defect in assembly and egress. These studies identify a novel host factor involved in virion production and a potential target for antiviral therapy. PMID:29093211

Sex-specific processing of social cues in the medial amygdala

PubMed Central

Bergan, Joseph F; Ben-Shaul, Yoram; Dulac, Catherine

2014-01-01

Animal–animal recognition within, and across species, is essential for predator avoidance and social interactions. Despite its essential role in orchestrating responses to animal cues, basic principles of information processing by the vomeronasal system are still unknown. The medial amygdala (MeA) occupies a central position in the vomeronasal pathway, upstream of hypothalamic centers dedicated to defensive and social responses. We have characterized sensory responses in the mouse MeA and uncovered emergent properties that shed new light onto the transformation of vomeronasal information into sex- and species-specific responses. In particular, we show that the MeA displays a degree of stimulus selectivity and a striking sexually dimorphic sensory representation that are not observed in the upstream relay of the accessory olfactory bulb (AOB). Furthermore, our results demonstrate that the development of sexually dimorphic circuits in the MeA requires steroid signaling near the time of puberty to organize the functional representation of sensory stimuli. DOI: http://dx.doi.org/10.7554/eLife.02743.001 PMID:24894465

Global Analysis of Yeast Endosomal Transport Identifies the Vps55/68 Sorting Complex

PubMed Central

Schluter, Cayetana; Lam, Karen K.Y.; Brumm, Jochen; Wu, Bella W.; Saunders, Matthew; Stevens, Tom H.

2008-01-01

Endosomal transport is critical for cellular processes ranging from receptor down-regulation and retroviral budding to the immune response. A full understanding of endosome sorting requires a comprehensive picture of the multiprotein complexes that orchestrate vesicle formation and fusion. Here, we use unsupervised, large-scale phenotypic analysis and a novel computational approach for the global identification of endosomal transport factors. This technique effectively identifies components of known and novel protein assemblies. We report the characterization of a previously undescribed endosome sorting complex that contains two well-conserved proteins with four predicted membrane-spanning domains. Vps55p and Vps68p form a complex that acts with or downstream of ESCRT function to regulate endosomal trafficking. Loss of Vps68p disrupts recycling to the TGN as well as onward trafficking to the vacuole without preventing the formation of lumenal vesicles within the MVB. Our results suggest the Vps55/68 complex mediates a novel, conserved step in the endosomal maturation process. PMID:18216282

Redox biology of the intestine

PubMed Central

Circu, Magdalena L.; Aw, Tak Yee

2011-01-01

The intestinal tract, known for its capability for self-renew, represents the first barrier of defense between the organism and its luminal environment. The thiol/disulfide redox systems comprising the glutathione/glutathione disulfide (GSH/GSSG), cysteine/cystine (Cys/CySS) and reduced and oxidized thioredoxin (Trx/TrxSS) redox couples play important roles in preserving tissue redox homeostasis, metabolic functions, and cellular integrity. Control of the thiol-disulfide status at the luminal surface is essential for maintaining mucus fluidity and absorption of nutrients, and protection against chemical-induced oxidant injury. Within intestinal cells, these redox couples preserve an environment that supports physiological processes and orchestrates networks of enzymatic reactions against oxidative stress. In this review, we focus on the intestinal redox and antioxidant systems, their subcellular compartmentation, redox signaling and epithelial turnover, and contribution of luminal microbiota, key aspects that are relevant to understanding redox-dependent processes in gut biology with implications for degenerative digestive disorders, such as inflammation and cancer. PMID:21831010

Novel lipid mediators promote resolution of acute inflammation: impact of aspirin and statins

PubMed Central

Spite, Matthew; Serhan, Charles N.

2010-01-01

The resolution of acute inflammation is a process that allows for inflamed tissues to return to homeostasis. Resolution was held to be a passive process, a concept now overturned with new evidence demonstrating that resolution is actively orchestrated by distinct cellular events and endogenous chemical mediators. Among these, lipid mediators, such as the lipoxins, resolvins, protectins and newly identified maresins, have emerged as a novel genus of potent and stereoselective players that counter-regulate excessive acute inflammation and stimulate molecular and cellular events that define resolution. Given that uncontrolled, chronic inflammation is associated with many cardiovascular pathologies, an appreciation of the endogenous pathways and mediators that control timely resolution can open new terrain for therapeutic approaches targeted at stimulating resolution of local inflammation, as well as correcting the impact of chronic inflammation in cardiovascular disorders. Here, we overview and update the biosynthesis and actions of pro-resolving lipid mediators, highlighting their diverse protective roles relevant to vascular systems and their relation to aspirin and statin therapies. PMID:21071715

CELSS research and development program

NASA Technical Reports Server (NTRS)

Bubenheim, David

1990-01-01

Research in Controlled Ecological Life Support Systems (CELSS) conducted by NASA indicate that plant based systems are feasible candidates for human support in space. Ames has responsibility for research and development, systems integration and control, and space flight experiment portions of the CELSS program. Important areas for development of new methods and technologies are biomass production, waste processing, water purification, air revitalization, and food processing. For the plant system, the approach was to identify the flexibility and response time for the food, water, and oxygen production, and carbon dioxide consumption processes. Tremendous increases in productivity, compared with terrestrial agriculture, were realized. Waste processing research emphasizes recycle (transformation) of human wastes, trash, and inedible biomass to forms usable as inputs to the plant production system. Efforts to improve efficiency of the plant system, select new CELSS crops for a balanced diet, and initiate closed system research with the Crop Growth Research Chambers continue. The System Control and Integration program goal is to insure orchestrated system operation of the biological, physical, and chemical operation of the biological, physical, and chemical component processors of the CELSS. Space flight studies are planned to verify adequate operation of the system in reduced gravity or microgravity environments.

DNA repair and aging: the impact of the p53 family.

PubMed

Nicolai, Sara; Rossi, Antonello; Di Daniele, Nicola; Melino, Gerry; Annicchiarico-Petruzzelli, Margherita; Raschellà, Giuseppe

2015-12-01

Cells are constantly exposed to endogenous and exogenous factors that threaten the integrity of their DNA. The maintenance of genome stability is of paramount importance in the prevention of both cancer and aging processes. To deal with DNA damage, cells put into operation a sophisticated and coordinated mechanism, collectively known as DNA damage response (DDR). The DDR orchestrates different cellular processes, such as DNA repair, senescence and apoptosis. Among the key factors of the DDR, the related proteins p53, p63 and p73, all belonging to the same family of transcription factors, play multiple relevant roles. Indeed, the members of this family are directly involved in the induction of cell cycle arrest that is necessary to allow the cells to repair. Alternatively, they can promote cell death in case of prolonged or irreparable DNA damage. They also take part in a more direct task by modulating the expression of core factors involved in the process of DNA repair or by directly interacting with them. In this review we will analyze the fundamental roles of the p53 family in the aging process through their multifaceted function in DDR.

DNA repair and aging: the impact of the p53 family

PubMed Central

Nicolai, Sara; Rossi, Antonello; Di Daniele, Nicola; Melino, Gerry; Annicchiarico-Petruzzelli, Margherita; Raschellà, Giuseppe

2015-01-01

Cells are constantly exposed to endogenous and exogenous factors that threaten the integrity of their DNA. The maintenance of genome stability is of paramount importance in the prevention of both cancer and aging processes. To deal with DNA damage, cells put into operation a sophisticated and coordinated mechanism, collectively known as DNA damage response (DDR). The DDR orchestrates different cellular processes, such as DNA repair, senescence and apoptosis. Among the key factors of the DDR, the related proteins p53, p63 and p73, all belonging to the same family of transcription factors, play multiple relevant roles. Indeed, the members of this family are directly involved in the induction of cell cycle arrest that is necessary to allow the cells to repair. Alternatively, they can promote cell death in case of prolonged or irreparable DNA damage. They also take part in a more direct task by modulating the expression of core factors involved in the process of DNA repair or by directly interacting with them. In this review we will analyze the fundamental roles of the p53 family in the aging process through their multifaceted function in DDR. PMID:26668111

An overview of the model integration process: From pre ...

EPA Pesticide Factsheets

Integration of models requires linking models which can be developed using different tools, methodologies, and assumptions. We performed a literature review with the aim of improving our understanding of model integration process, and also presenting better strategies for building integrated modeling systems. We identified five different phases to characterize integration process: pre-integration assessment, preparation of models for integration, orchestration of models during simulation, data interoperability, and testing. Commonly, there is little reuse of existing frameworks beyond the development teams and not much sharing of science components across frameworks. We believe this must change to enable researchers and assessors to form complex workflows that leverage the current environmental science available. In this paper, we characterize the model integration process and compare integration practices of different groups. We highlight key strategies, features, standards, and practices that can be employed by developers to increase reuse and interoperability of science software components and systems. The paper provides a review of the literature regarding techniques and methods employed by various modeling system developers to facilitate science software interoperability. The intent of the paper is to illustrate the wide variation in methods and the limiting effect the variation has on inter-framework reuse and interoperability. A series of recommendation

Advances of Stem Cell Therapeutics in Cutaneous Wound Healing and Regeneration

PubMed Central

Kanji, Suman

2017-01-01

Cutaneous wound healing is a complex multiple phase process, which overlaps each other, where several growth factors, cytokines, chemokines, and various cells interact in a well-orchestrated manner. However, an imbalance in any of these phases and factors may lead to disruption in harmony of normal wound healing process, resulting in transformation towards chronic nonhealing wounds and abnormal scar formation. Although various therapeutic interventions are available to treat chronic wounds, current wound-care has met with limited success. Progenitor stem cells possess potential therapeutic ability to overcome limitations of the present treatments as it offers accelerated wound repair with tissue regeneration. A substantial number of stem cell therapies for cutaneous wounds are currently under development as a result of encouraging preliminary findings in both preclinical and clinical studies. However, the mechanisms by which these stem cells contribute to the healing process have yet to be elucidated. In this review, we emphasize on the major treatment modalities currently available for the treatment of the wound, role of various interstitial stem cells and exogenous adult stem cells in cutaneous wound healing, and possible mechanisms involved in the healing process. PMID:29213192

Coexpression network based on natural variation in human gene expression reveals gene interactions and functions

PubMed Central

Nayak, Renuka R.; Kearns, Michael; Spielman, Richard S.; Cheung, Vivian G.

2009-01-01

Genes interact in networks to orchestrate cellular processes. Analysis of these networks provides insights into gene interactions and functions. Here, we took advantage of normal variation in human gene expression to infer gene networks, which we constructed using correlations in expression levels of more than 8.5 million gene pairs in immortalized B cells from three independent samples. The resulting networks allowed us to identify biological processes and gene functions. Among the biological pathways, we found processes such as translation and glycolysis that co-occur in the same subnetworks. We predicted the functions of poorly characterized genes, including CHCHD2 and TMEM111, and provided experimental evidence that TMEM111 is part of the endoplasmic reticulum-associated secretory pathway. We also found that IFIH1, a susceptibility gene of type 1 diabetes, interacts with YES1, which plays a role in glucose transport. Furthermore, genes that predispose to the same diseases are clustered nonrandomly in the coexpression network, suggesting that networks can provide candidate genes that influence disease susceptibility. Therefore, our analysis of gene coexpression networks offers information on the role of human genes in normal and disease processes. PMID:19797678

A three dimensional micropatterned tumor model for breast cancer cell migration studies.

PubMed

Peela, Nitish; Sam, Feba S; Christenson, Wayne; Truong, Danh; Watson, Adam W; Mouneimne, Ghassan; Ros, Robert; Nikkhah, Mehdi

2016-03-01

Breast cancer cell invasion is a highly orchestrated process driven by a myriad of complex microenvironmental stimuli, making it difficult to isolate and assess the effects of biochemical or biophysical cues (i.e. tumor architecture, matrix stiffness) on disease progression. In this regard, physiologically relevant tumor models are becoming instrumental to perform studies of cancer cell invasion within well-controlled conditions. Herein, we explored the use of photocrosslinkable hydrogels and a novel, two-step photolithography technique to microengineer a 3D breast tumor model. The microfabrication process enabled precise localization of cell-encapsulated circular constructs adjacent to a low stiffness matrix. To validate the model, breast cancer cell lines (MDA-MB-231, MCF7) and non-tumorigenic mammary epithelial cells (MCF10A) were embedded separately within the tumor model, all of which maintained high viability throughout the experiments. MDA-MB-231 cells exhibited extensive migratory behavior and invaded the surrounding matrix, whereas MCF7 or MCF10A cells formed clusters that stayed confined within the circular tumor regions. Additionally, real-time cell tracking indicated that the speed and persistence of MDA-MB-231 cells were substantially higher within the surrounding matrix compared to the circular constructs. Z-stack imaging of F-actin/α-tubulin cytoskeletal organization revealed unique 3D protrusions in MDA-MB-231 cells and an abundance of 3D clusters formed by MCF7 and MCF10A cells. Our results indicate that gelatin methacrylate (GelMA) hydrogel, integrated with the two-step photolithography technique, has great promise in the development of 3D tumor models with well-defined architecture and tunable stiffness. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transformational System Concepts and Technologies for Our Future in Space

NASA Technical Reports Server (NTRS)

Howell, Joe T.; Mankins, John C.

2004-01-01

Continued constrained budgets and growing national and international interests in the commercialization and development of space requires NASA to be constantly vigilant, to be creative, and to seize every opportunity for assuring the maximum return on space infrastructure investments. Accordingly, efforts are underway to forge new and innovative approaches to transform our space systems in the future to ultimately achieve two or three or five times as much with the same resources. This bold undertaking can be achieved only through extensive cooperative efforts throughout the aerospace community and truly effective planning to pursue advanced space system design concepts and high-risk/high-leverage research and technology. Definitive implementation strategies and roadmaps containing new methodologies and revolutionary approaches must be developed to economically accommodate the continued exploration and development of space. Transformation can be realized through modular design and stepping stone development. This approach involves sustainable budget levels and multi-purpose systems development of supporting capabilities that lead to a diverse amy of sustainable future space activities. Transformational design and development requires revolutionary advances by using modular designs and a planned, stepping stone development process. A modular approach to space systems potentially offers many improvements over traditional one-of-a-kind space systems comprised of different subsystem element with little standardization in interfaces or functionality. Modular systems must be more flexible, scaleable, reconfigurable, and evolvable. Costs can be reduced through learning curve effects and economies of scale, and by enabling servicing and repair that would not otherwise be feasible. This paper briefly discusses achieving a promising approach to transforming space systems planning and evolution into a meaningful stepping stone design, development, and implementation process. The success of this well planned and orchestrated approach holds great promise for achieving innovation and revolutionary technology development for supporting future exploration and development of space.

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

PubMed

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

2009-01-01

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

Regulation of Yersina pestis Virulence by AI-2 Mediated Quorum Sensing

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

Segelke, B; Hok, S; Lao, V

The proposed research was motivated by an interest in understanding Y. pestis virulence mechanisms and bacteria cell-cell communication. It is expected that a greater understanding of virulence mechanisms will ultimately lead to biothreat countermeasures and novel therapeutics. Y. pestis is the etiological agent of plague, the most devastating disease in human history. Y. pestis infection has a high mortality rate and a short incubation before mortality. There is no widely available and effective vaccine for Y. pestis and multi-drug resistant strains are emerging. Y. pestis is a recognized biothreat agent based on the wide distribution of the bacteria in researchmore » laboratories around the world and on the knowledge that methods exist to produce and aerosolize large amounts of bacteria. We hypothesized that cell-cell communication via signaling molecules, or quorum sensing, by Y. pestis is important for the regulation of virulence factor gene expression during host invasion, though a causative link had never been established. Quorum sensing is a mode of intercellular communication which enables orchestration of gene expression for many bacteria as a function of population density and available evidence suggests there may be a link between quorum sensing and regulation of Y. pesits virulence. Several pathogenic bacteria have been shown to regulate expression of virulence factor genes, including genes encoding type III secretion, via quorum sensing. The Y. pestis genome encodes several cell-cell signaling pathways and the interaction of at least three of these are thought to be involved in one or more modes of host invasion. Furthermore, Y. pestis gene expression array studies carried out at LLNL have established a correlation between expression of known virulence factors and genes involved in processing of the AI-2 quorum sensing signal. This was a basic research project that was intended to provide new insights into bacterial intercellular communication and how it is used to regulate virulence in Y. pestis. It is known that many bacteria use intercellular signaling molecules to orchestrate gene expression and cellular function. A fair amount is known about production and uptake of signaling molecules, but very little is known about how intercellular signaling regulates other pathways. Although several studies demonstrate that intercellular signaling plays a role in regulating virulence in other pathogens, the link between signaling and regulation of virulence has not been established. Very little work had been done directly with Y. pestis intercellular signaling apart from the work carried out at LLNL. The research we proposed was intended to both establish a causative link between AI-2 intercellular signaling and regulation of virulence in Y. pestis and elucidate the fate of the AI-2 signaling molecule after it is taken up and processed by Y. pestis. Elucidating the fate of AI-2 was expected to lead directly to the understanding of how AI-2 signal processing regulates other pathways as well as provide new insights in this direction.« less

Osmotic Stress Signaling and Osmoadaptation in Yeasts

PubMed Central

Hohmann, Stefan

2002-01-01

The ability to adapt to altered availability of free water is a fundamental property of living cells. The principles underlying osmoadaptation are well conserved. The yeast Saccharomyces cerevisiae is an excellent model system with which to study the molecular biology and physiology of osmoadaptation. Upon a shift to high osmolarity, yeast cells rapidly stimulate a mitogen-activated protein (MAP) kinase cascade, the high-osmolarity glycerol (HOG) pathway, which orchestrates part of the transcriptional response. The dynamic operation of the HOG pathway has been well studied, and similar osmosensing pathways exist in other eukaryotes. Protein kinase A, which seems to mediate a response to diverse stress conditions, is also involved in the transcriptional response program. Expression changes after a shift to high osmolarity aim at adjusting metabolism and the production of cellular protectants. Accumulation of the osmolyte glycerol, which is also controlled by altering transmembrane glycerol transport, is of central importance. Upon a shift from high to low osmolarity, yeast cells stimulate a different MAP kinase cascade, the cell integrity pathway. The transcriptional program upon hypo-osmotic shock seems to aim at adjusting cell surface properties. Rapid export of glycerol is an important event in adaptation to low osmolarity. Osmoadaptation, adjustment of cell surface properties, and the control of cell morphogenesis, growth, and proliferation are highly coordinated processes. The Skn7p response regulator may be involved in coordinating these events. An integrated understanding of osmoadaptation requires not only knowledge of the function of many uncharacterized genes but also further insight into the time line of events, their interdependence, their dynamics, and their spatial organization as well as the importance of subtle effects. PMID:12040128

Cuticular Biominerals of the Terrestrial Crustacean Oniscus asellus (Isopoda, Linnaeus 1758)

NASA Astrophysics Data System (ADS)

Mergelsberg, S. T.; Mukhopadhyay, B.; Dove, P. M.

2013-12-01

Biomineralization is a phenomenon observed in many eukaryotic organisms and evidence suggests this process began relatively early in the evolution of multicellular life (Marin F et al. 1996). Crustaceans form a large fraction of all eukaryotic biomineralizers by incorporating calcium carbonate (CaCO3) into their cuticle. Terrestrial species are challenged in their production of CaCO3 by the absence of calcium-rich waters. To cope with this limitation, the terrestrial crustacean Oniscus asellus recycles up to 80% (Auzou G 1953) of its total calcium during the molting process. This feat is accomplished by separate molting of the front and back cuticle, with temporary storage of the calcium carbonate as amorphous calcium carbonate (ACC) in the front half (Ziegler A 1997). These processes infer a highly efficient and regulated mechanism for biomineralization that is most likely orchestrated by a myriad of proteins (Ziegler A et al. 2012). Until recently, investigations of biomineralization were largely directed toward understanding morphology and large-scale chemistry of the minerals, ignoring the mechanistic roles of biomacromolecules in mineralization processes. More recent work suggests a high involvement of these compounds on the formation of biominerals and, in some cases, the specific polymorphs thereof (Keene EC et al. 2010). This study focuses on identifying the components of the biological mineralization matrix at each stage of the process. Using chemical demineralization of the stored ACC, all biomacromolecules can be separated and purified for subsequent analysis by MALDI-TOF mass spectrometry. To link the localized biochemistry more intimately to the polymorph of calcium carbonate that forms in the animal, the inorganic phase (';the mineral') will be monitored at each life stage using XRD and TEM. This analysis will reveal the organic components of a very precise biomineralization mechanism and may shed insight on its evolutionary origin. References: Marin F, Westbroek P et al., 1996, Proc Nat Acad Sci 93:1554-1559 Auzou G, 1953, L Ann Sci Nat 15:71-98 Ziegler A, 1997, Zoomorphology 117:181-187 Ziegler A et al., 2012, Cryst Growth Des 12:646-655 Keene EC et al., 2010, Cryst Growth Des 10:1383-1389

Acetylcholine Release in Prefrontal Cortex Promotes Gamma Oscillations and Theta–Gamma Coupling during Cue Detection

PubMed Central

Hetrick, Vaughn L.; Berke, Joshua D.

2017-01-01

The capacity for using external cues to guide behavior (“cue detection”) constitutes an essential aspect of attention and goal-directed behavior. The cortical cholinergic input system, via phasic increases in prefrontal acetylcholine release, plays an essential role in attention by mediating such cue detection. However, the relationship between cholinergic signaling during cue detection and neural activity dynamics in prefrontal networks remains unclear. Here we combined subsecond measures of cholinergic signaling, neurophysiological recordings, and cholinergic receptor blockade to delineate the cholinergic contributions to prefrontal oscillations during cue detection in rats. We first confirmed that detected cues evoke phasic acetylcholine release. These cholinergic signals were coincident with increased neuronal synchrony across several frequency bands and the emergence of theta–gamma coupling. Muscarinic and nicotinic cholinergic receptors both contributed specifically to gamma synchrony evoked by detected cues, but the effects of blocking the two receptor subtypes were dissociable. Blocking nicotinic receptors primarily attenuated high-gamma oscillations occurring during the earliest phases of the cue detection process, while muscarinic (M1) receptor activity was preferentially involved in the transition from high to low gamma power that followed and corresponded to the mobilization of networks involved in cue-guided decision making. Detected cues also promoted coupling between gamma and theta oscillations, and both nicotinic and muscarinic receptor activity contributed to this process. These results indicate that acetylcholine release coordinates neural oscillations during the process of cue detection. SIGNIFICANCE STATEMENT The capacity of learned cues to direct attention and guide responding (“cue detection”) is a key component of goal-directed behavior. Rhythmic neural activity and increases in acetylcholine release in the prefrontal cortex contribute to this process; however, the relationship between these neuronal mechanisms is not well understood. Using a combination of in vivo neurochemistry, neurophysiology, and pharmacological methods, we demonstrate that cue-evoked acetylcholine release, through distinct actions at both nicotinic and muscarinic receptors, triggers a procession of neural oscillations that map onto the multiple stages of cue detection. Our data offer new insights into cholinergic function by revealing the temporally orchestrated changes in prefrontal network synchrony modulated by acetylcholine release during cue detection. PMID:28213446

The chromatin basis of neurodevelopmental disorders: Rethinking dysfunction along the molecular and temporal axes.

PubMed

Gabriele, Michele; Lopez Tobon, Alejandro; D'Agostino, Giuseppe; Testa, Giuseppe

2018-06-08

The complexity of the human brain emerges from a long and finely tuned developmental process orchestrated by the crosstalk between genome and environment. Vis à vis other species, the human brain displays unique functional and morphological features that result from this extensive developmental process that is, unsurprisingly, highly vulnerable to both genetically and environmentally induced alterations. One of the most striking outcomes of the recent surge of sequencing-based studies on neurodevelopmental disorders (NDDs) is the emergence of chromatin regulation as one of the two domains most affected by causative mutations or Copy Number Variations besides synaptic function, whose involvement had been largely predicted for obvious reasons. These observations place chromatin dysfunction at the top of the molecular pathways hierarchy that ushers in a sizeable proportion of NDDs and that manifest themselves through synaptic dysfunction and recurrent systemic clinical manifestation. Here we undertake a conceptual investigation of chromatin dysfunction in NDDs with the aim of systematizing the available evidence in a new framework: first, we tease out the developmental vulnerabilities in human corticogenesis as a structuring entry point into the causation of NDDs; second, we provide a much needed clarification of the multiple meanings and explanatory frameworks revolving around "epigenetics", highlighting those that are most relevant for the analysis of these disorders; finally we go in-depth into paradigmatic examples of NDD-causing chromatin dysregulation, with a special focus on human experimental models and datasets. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

In vitro models for evaluation of periodontal wound healing/regeneration.

PubMed

Weinreb, Miron; Nemcovsky, Carlos E

2015-06-01

Periodontal wound healing and regeneration are highly complex processes, involving cells, matrices, molecules and genes that must be properly choreographed and orchestrated. As we attempt to understand and influence these clinical entities, we need experimental models to mimic the various aspects of human wound healing and regeneration. In vivo animal models that simulate clinical situations of humans can be costly and cumbersome. In vitro models have been devised to dissect wound healing/regeneration processes into discrete, analyzable steps. For soft tissue (e.g. gingival) healing, in vitro models range from simple culture of cells grown in monolayers and exposed to biological modulators or physical effectors and materials, to models in which cells are 'injured' by scraping and subsequently the 'wound' is filled with new or migrating cells, to three-dimensional models of epithelial-mesenchymal recombination or tissue explants. The cells employed are gingival keratinocytes, fibroblasts or endothelial cells, and their proliferation, migration, attachment, differentiation, survival, gene expression, matrix production or capillary formation are measured. Studies of periodontal regeneration also include periodontal ligament fibroblasts or progenitors, osteoblasts or osteoprogenitors, and cementoblasts. Regeneration models measure cellular proliferation, attachment and migration, as well as gene expression, transfer and differentiation into a mineralizing phenotype and biomineralization. Only by integrating data from models on all levels (i.e. a single cell to the whole organism) can various critical aspects of periodontal wound healing/regeneration be fully evaluated. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Glycogen Synthase Kinase 3β Dictates Podocyte Motility and Focal Adhesion Turnover by Modulating Paxillin Activity

PubMed Central

Xu, Weiwei; Ge, Yan; Liu, Zhihong; Gong, Rujun

2015-01-01

Aberrant focal adhesion turnover is centrally involved in podocyte actin cytoskeleton disorganization and foot process effacement. The structural and dynamic integrity of focal adhesions is orchestrated by multiple cell signaling molecules, including glycogen synthase kinase 3β (GSK3β), a multitasking kinase lately identified as a mediator of kidney injury. However, the role of GSK3β in podocytopathy remains obscure. In doxorubicin (Adriamycin)-injured podocytes, lithium, a GSK3β inhibitor and neuroprotective mood stabilizer, obliterated the accelerated focal adhesion turnover, rectified podocyte hypermotility, and restored actin cytoskeleton integrity. Mechanistically, lithium counteracted the doxorubicin-elicited GSK3β overactivity and the hyperphosphorylation and overactivation of paxillin, a focal adhesion–associated adaptor protein. Moreover, forced expression of a dominant negative kinase dead mutant of GSK3β highly mimicked, whereas ectopic expression of a constitutively active GSK3β mutant abolished, the effect of lithium in doxorubicin-injured podocytes, suggesting that the effect of lithium is mediated, at least in part, through inhibition of GSK3β. Furthermore, paxillin interacted with GSK3β and served as its substrate. In mice with doxorubicin nephropathy, a single low dose of lithium ameliorated proteinuria and glomerulosclerosis. Consistently, lithium therapy abrogated GSK3β overactivity, blunted paxillin hyperphosphorylation, and reinstated actin cytoskeleton integrity in glomeruli associated with an early attenuation of podocyte foot process effacement. Thus, GSK3β-modulated focal adhesion dynamics might serve as a novel therapeutic target for podocytopathy. PMID:25239564

Genome organization during the cell cycle: unity in division.

PubMed

Golloshi, Rosela; Sanders, Jacob T; McCord, Rachel Patton

2017-09-01

During the cell cycle, the genome must undergo dramatic changes in structure, from a decondensed, yet highly organized interphase structure to a condensed, generic mitotic chromosome and then back again. For faithful cell division, the genome must be replicated and chromosomes and sister chromatids physically segregated from one another. Throughout these processes, there is feedback and tension between the information-storing role and the physical properties of chromosomes. With a combination of recent techniques in fluorescence microscopy, chromosome conformation capture (Hi-C), biophysical experiments, and computational modeling, we can now attribute mechanisms to many long-observed features of chromosome structure changes during cell division. Apparent conflicts that arise when integrating the concepts from these different proposed mechanisms emphasize that orchestrating chromosome organization during cell division requires a complex system of factors rather than a simple pathway. Cell division is both essential for and threatening to proper genome organization. As interphase three-dimensional (3D) genome structure is quite static at a global level, cell division provides an important window of opportunity to make substantial changes in 3D genome organization in daughter cells, allowing for proper differentiation and development. Mistakes in the process of chromosome condensation or rebuilding the structure after mitosis can lead to diseases such as cancer, premature aging, and neurodegeneration. WIREs Syst Biol Med 2017, 9:e1389. doi: 10.1002/wsbm.1389 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Lost in Translation

ERIC Educational Resources Information Center

Thompson, Jane

2004-01-01

A conference event is mediated through keynote speeches, power point presentations, professional role-playing and the turgid language of policy agendas, initiatives, benchmarks and outputs. Serious human concerns rarely surface in the orchestrated and anodyne arena of professional conference-going. The ready recourse to ritual and procedure means…

Authoring and Enactment of Mobile Pyramid-Based Collaborative Learning Activities

ERIC Educational Resources Information Center

Manathunga, Kalpani; Hernández-Leo, Davinia

2018-01-01

Collaborative learning flow patterns (CLFPs) formulate best practices for the orchestration of activity sequences and collaboration mechanisms that can elicit fruitful social interactions. Mobile technology features offer opportunities to support interaction mediation and content accessibility. However, existing mobile collaborative learning…

Aligning the PRME: How Study Abroad Nurtures Responsible Leadership

ERIC Educational Resources Information Center

Sroufe, Robert; Sivasubramaniam, Nagaraj; Ramos, Diane; Saiia, David

2015-01-01

Productive relationships between business schools and corporate organizations provide fertile ground for bringing business leaders, faculty, students, and community partners face-to-face with contemporaries abroad to foster development of responsible global leadership competencies. While well-orchestrated multicountry collaboration offers unique…

Theoretical Frameworks to Guide School Improvement

ERIC Educational Resources Information Center

Evans, Lisa; Thornton, Bill; Usinger, Janet

2012-01-01

A firm grounding in change theory can provide educational leaders with an opportunity to orchestrate meaningful organizational improvements. This article provides an opportunity for practicing leaders to review four major theories of organizational change--continuous improvement, two approaches to organizational learning, and appreciative inquiry.…

In Vivo Assessment of Protease Dynamics in Cutaneous Wound Healing by Degradomics Analysis of Porcine Wound Exudates*

PubMed Central

Sabino, Fabio; Hermes, Olivia; Egli, Fabian E.; Kockmann, Tobias; Schlage, Pascal; Croizat, Pierre; Kizhakkedathu, Jayachandran N.; Smola, Hans; auf dem Keller, Ulrich

2015-01-01

Proteases control complex tissue responses by modulating inflammation, cell proliferation and migration, and matrix remodeling. All these processes are orchestrated in cutaneous wound healing to restore the skin's barrier function upon injury. Altered protease activity has been implicated in the pathogenesis of healing impairments, and proteases are important targets in diagnosis and therapy of this pathology. Global assessment of proteolysis at critical turning points after injury will define crucial events in acute healing that might be disturbed in healing disorders. As optimal biospecimens, wound exudates contain an ideal proteome to detect extracellular proteolytic events, are noninvasively accessible, and can be collected at multiple time points along the healing process from the same wound in the clinics. In this study, we applied multiplexed Terminal Amine Isotopic Labeling of Substrates (TAILS) to globally assess proteolysis in early phases of cutaneous wound healing. By quantitative analysis of proteins and protein N termini in wound fluids from a clinically relevant pig wound model, we identified more than 650 proteins and discerned major healing phases through distinctive abundance clustering of markers of inflammation, granulation tissue formation, and re-epithelialization. TAILS revealed a high degree of proteolysis at all time points after injury by detecting almost 1300 N-terminal peptides in ∼450 proteins. Quantitative positional proteomics mapped pivotal interdependent processing events in the blood coagulation and complement cascades, temporally discerned clotting and fibrinolysis during the healing process, and detected processing of complement C3 at distinct time points after wounding and by different proteases. Exploiting data on primary cleavage specificities, we related candidate proteases to cleavage events and revealed processing of the integrin adapter protein kindlin-3 by caspase-3, generating new hypotheses for protease-substrate relations in the healing skin wound in vivo. The data have been deposited to the ProteomeXchange Consortium with identifier PXD001198. PMID:25516628

BioVLAB-MMIA: a cloud environment for microRNA and mRNA integrated analysis (MMIA) on Amazon EC2.

PubMed

Lee, Hyungro; Yang, Youngik; Chae, Heejoon; Nam, Seungyoon; Choi, Donghoon; Tangchaisin, Patanachai; Herath, Chathura; Marru, Suresh; Nephew, Kenneth P; Kim, Sun

2012-09-01

MicroRNAs, by regulating the expression of hundreds of target genes, play critical roles in developmental biology and the etiology of numerous diseases, including cancer. As a vast amount of microRNA expression profile data are now publicly available, the integration of microRNA expression data sets with gene expression profiles is a key research problem in life science research. However, the ability to conduct genome-wide microRNA-mRNA (gene) integration currently requires sophisticated, high-end informatics tools, significant expertise in bioinformatics and computer science to carry out the complex integration analysis. In addition, increased computing infrastructure capabilities are essential in order to accommodate large data sets. In this study, we have extended the BioVLAB cloud workbench to develop an environment for the integrated analysis of microRNA and mRNA expression data, named BioVLAB-MMIA. The workbench facilitates computations on the Amazon EC2 and S3 resources orchestrated by the XBaya Workflow Suite. The advantages of BioVLAB-MMIA over the web-based MMIA system include: 1) readily expanded as new computational tools become available; 2) easily modifiable by re-configuring graphic icons in the workflow; 3) on-demand cloud computing resources can be used on an "as needed" basis; 4) distributed orchestration supports complex and long running workflows asynchronously. We believe that BioVLAB-MMIA will be an easy-to-use computing environment for researchers who plan to perform genome-wide microRNA-mRNA (gene) integrated analysis tasks.

Distant homologs of anti-apoptotic factor HAX1 encode parvalbumin-like calcium binding proteins.

PubMed

Kokoszyńska, Katarzyna; Rychlewski, Leszek; Wyrwicz, Lucjan S

2010-07-15

Apoptosis is a highly ordered and orchestrated multiphase process controlled by the numerous cellular and extra-cellular signals, which executes the programmed cell death via release of cytochrome c alterations in calcium signaling, caspase-dependent limited proteolysis and DNA fragmentation. Besides the general modifiers of apoptosis, several tissue-specific regulators of this process were identified including HAX1 (HS-1 associated protein X-1) - an anti-apoptotic factor active in myeloid cells. Although HAX1 was the subject of various experimental studies, the mechanisms of its action and a functional link connected with the regulation of apoptosis still remains highly speculative. Here we provide the data which suggests that HAX1 may act as a regulator or as a sensor of calcium. On the basis of iterative similarity searches, we identified a set of distant homologs of HAX1 in insects. The applied fold recognition protocol gives us strong evidence that the distant insects' homologs of HAX1 are novel parvalbumin-like calcium binding proteins. Although the whole three EF-hands fold is not preserved in vertebrate our analysis suggests that there is an existence of a potential single EF-hand calcium binding site in HAX1. The molecular mechanism of its action remains to be identified, but the risen hypothesis easily translates into previously reported lines of various data on the HAX1 biology as well as, provides us a direct link to the regulation of apoptosis. Moreover, we also report that other family of myeloid specific apoptosis regulators - myeloid leukemia factors (MLF1, MLF2) share the homologous C-terminal domain and taxonomic distribution with HAX1. Performed structural and active sites analyses gave new insights into mechanisms of HAX1 and MLF families in apoptosis process and suggested possible role of HAX1 in calcium-binding, still the analyses require further experimental verification.

Distant homologs of anti-apoptotic factor HAX1 encode parvalbumin-like calcium binding proteins

PubMed Central

2010-01-01

Background Apoptosis is a highly ordered and orchestrated multiphase process controlled by the numerous cellular and extra-cellular signals, which executes the programmed cell death via release of cytochrome c alterations in calcium signaling, caspase-dependent limited proteolysis and DNA fragmentation. Besides the general modifiers of apoptosis, several tissue-specific regulators of this process were identified including HAX1 (HS-1 associated protein X-1) - an anti-apoptotic factor active in myeloid cells. Although HAX1 was the subject of various experimental studies, the mechanisms of its action and a functional link connected with the regulation of apoptosis still remains highly speculative. Findings Here we provide the data which suggests that HAX1 may act as a regulator or as a sensor of calcium. On the basis of iterative similarity searches, we identified a set of distant homologs of HAX1 in insects. The applied fold recognition protocol gives us strong evidence that the distant insects' homologs of HAX1 are novel parvalbumin-like calcium binding proteins. Although the whole three EF-hands fold is not preserved in vertebrate our analysis suggests that there is an existence of a potential single EF-hand calcium binding site in HAX1. The molecular mechanism of its action remains to be identified, but the risen hypothesis easily translates into previously reported lines of various data on the HAX1 biology as well as, provides us a direct link to the regulation of apoptosis. Moreover, we also report that other family of myeloid specific apoptosis regulators - myeloid leukemia factors (MLF1, MLF2) share the homologous C-terminal domain and taxonomic distribution with HAX1. Conclusions Performed structural and active sites analyses gave new insights into mechanisms of HAX1 and MLF families in apoptosis process and suggested possible role of HAX1 in calcium-binding, still the analyses require further experimental verification. PMID:20633251

Professional Orchestral Conductors' Use of Selected Teaching Behaviors in Rehearsal

ERIC Educational Resources Information Center

Whitaker, Jennifer A.

2017-01-01

This descriptive study examined professional conductors' use of rehearsal time in sequential pattern components, discussing task presentation targets, and using verbal imagery and modeling techniques. Commercially available videos of 15 professional conductors rehearsing prominent orchestras were scripted, coded, and timed for selected teaching…

Handbook for Teaching Korean-American Students.

ERIC Educational Resources Information Center

California State Dept. of Education, Sacramento. Bilingual Education Office.

This handbook is designed for teachers, administrators, and other school personnel. It provides an explanation of the sociocultural and linguistic characteristics of Korean-Americans so educators can address their needs more effectively and orchestrate a better teaching environment by understanding and supporting the Korean-American cultural…

Orchestrating Multiple Intelligences

ERIC Educational Resources Information Center

Moran, Seana; Kornhaber, Mindy; Gardner, Howard

2006-01-01

Education policymakers often go astray when they attempt to integrate multiple intelligences theory into schools, according to the originator of the theory, Howard Gardner, and his colleagues. The greatest potential of a multiple intelligences approach to education grows from the concept of a profile of intelligences. Each learner's intelligence…

The Mediation of Acculturation: Orchestrating School Leadership Development in England

ERIC Educational Resources Information Center

Wallace, Mike; Tomlinson, Michael; O'Reilly, Dermot

2011-01-01

Among western governments large-scale leadership development initiatives represent an increasingly deployed means of promoting the acculturation of school leaders to support educational reforms and ongoing improvement. England's sophisticated initiative centres on the National College for Leadership in Schools and Children's Services, a…

Epithelial cells from smokers modify dendritic cell responses in the context of influenza infection

EPA Science Inventory

Epidemiologic evidence suggests that cigarette smoking is a risk factor for infection with influenza, but the mechanisms underlying this susceptibility remain unknown. To ascertain if airway epithelial cells from smokers demonstrate a decreased ability to orchestrate an influenza...

Orchestrating Semiotic Resources in Explicit Strategy Instruction

ERIC Educational Resources Information Center

Shanahan, Lynn E.; Flury-Kashmanian, Caroline

2014-01-01

Research and pedagogical information provided to teachers on implementing explicit strategy instruction has primarily focused on teachers' speech, with limited attention to other modes of communication, such as gesture and artefacts. This interpretive case study investigates two teachers' use of different semiotic resources when introducing…

Orchestrating Inquiry Learning

ERIC Educational Resources Information Center

Littleton, Karen, Ed.; Scanlon, Eileen, Ed.; Sharples, Mike, Ed.

2011-01-01

There is currently a rapidly growing interest in inquiry learning and an emerging consensus among researchers that, particularly when supported by technology, it can be a significant vehicle for developing higher order thinking skills. Inquiry learning methods also offer learners meaningful and productive approaches to the development of their…

Research in Corporate Communication: An Overview of an Emerging Field.

ERIC Educational Resources Information Center

van Riel, Cees B. M.

1997-01-01

Provides an overview of research in corporate communication, focusing on achievements found in the international academic literature in both communication and business school disciplines. Gives three key concepts in such research: corporate identity, corporate reputation, and orchestration of communication. Advocates an interdisciplinary approach…

Programming for Adolescents with Behavioral Disorders, Vol. 5.

ERIC Educational Resources Information Center

Braaten, Sheldon L., Ed.; Wild, Estelle, Ed.

This collection of 13 author-contributed papers addresses various aspects of programming for students with behavioral disorders. Papers have the following titles and authors: (1) "System Support and Transition to Adulthood for Adolescents with Seriously Disordered Behaviors: Orchestrating Successful Transitions" (Eugene Edgar); (2) "Targets for…

Tackling Misconceptions about Linear Associations

ERIC Educational Resources Information Center

Huey, Maryann E.; Baker, Deidra L.

2015-01-01

Many teachers of required secondary school mathematics classes are introducing statistics and probability topics traditionally relegated to college or AP Statistics courses. As a result, they need guidance in preparing lesson plans and orchestrating effective classroom discussions. In this article, the authors will describe the students' learning…

Interaction with Epithelial Cells Modifies Airway Macrophage Response to Ozone

EPA Science Inventory

The initial innate immune response to ozone (03) in the lung is orchestrated by structural cells, such as epithelial cells, and resident immune cells, such as airway macrophages (Macs). We developed an epithelial cell-Mac coculture model to investigate how epithelial cell-derived...

A Decrease in Ambient Temperature Induces Post-Mitotic Enlargement of Palisade Cells in North American Lake Cress.

PubMed

Amano, Rumi; Nakayama, Hokuto; Morohoshi, Yurika; Kawakatsu, Yaichi; Ferjani, Ali; Kimura, Seisuke

2015-01-01

In order to maintain organs and structures at their appropriate sizes, multicellular organisms orchestrate cell proliferation and post-mitotic cell expansion during morphogenesis. Recent studies using Arabidopsis leaves have shown that compensation, which is defined as post-mitotic cell expansion induced by a decrease in the number of cells during lateral organ development, is one example of such orchestration. Some of the basic molecular mechanisms underlying compensation have been revealed by genetic and chimeric analyses. However, to date, compensation had been observed only in mutants, transgenics, and γ-ray-treated plants, and it was unclear whether it occurs in plants under natural conditions. Here, we illustrate that a shift in ambient temperature could induce compensation in Rorippa aquatica (Brassicaceae), a semi-aquatic plant found in North America. The results suggest that compensation is a universal phenomenon among angiosperms and that the mechanism underlying compensation is shared, in part, between Arabidopsis and R. aquatica.

A Decrease in Ambient Temperature Induces Post-Mitotic Enlargement of Palisade Cells in North American Lake Cress

PubMed Central

Morohoshi, Yurika; Kawakatsu, Yaichi; Ferjani, Ali; Kimura, Seisuke

2015-01-01

In order to maintain organs and structures at their appropriate sizes, multicellular organisms orchestrate cell proliferation and post-mitotic cell expansion during morphogenesis. Recent studies using Arabidopsis leaves have shown that compensation, which is defined as post-mitotic cell expansion induced by a decrease in the number of cells during lateral organ development, is one example of such orchestration. Some of the basic molecular mechanisms underlying compensation have been revealed by genetic and chimeric analyses. However, to date, compensation had been observed only in mutants, transgenics, and γ-ray–treated plants, and it was unclear whether it occurs in plants under natural conditions. Here, we illustrate that a shift in ambient temperature could induce compensation in Rorippa aquatica (Brassicaceae), a semi-aquatic plant found in North America. The results suggest that compensation is a universal phenomenon among angiosperms and that the mechanism underlying compensation is shared, in part, between Arabidopsis and R. aquatica. PMID:26569502

Religion as dialogical resource: a socio-cultural approach.

PubMed

Baucal, Aleksandar; Zittoun, Tania

2013-06-01

William James proposed a psychological study of religion examining people's religious experiences, and to see in what sense these were good for them. The recent developments of psychology of religion moved far from that initial proposition. In this paper, we propose a sociocultural perspective to religion that renews with that initial stance. After recalling Vygtotsky's core ideas, we suggest that religion, as cultural and symbolic system, participates to the orchestration of human activities and sense-making. Such orchestration works both from within the person, through internalized values and ideas, and from without, through the person's interactions with others, discourses, cultural objects etc. This leads us to consider religions as supporting various forms of dialogical dynamics-intra-psychological dialogues, interpersonal with present, absent or imaginary others, as well as inter-group dialogues-which we illustrate with empirical vignettes. The example of religious tensions in the Balkans in the 90's highlights how much the historical-cultural embeddedness of these dynamics can also lead to the end of dialogicality, and therefore, sense-making.

Keratinocytes as sensors and central players in the immune defense against Staphylococcus aureus in the skin.

PubMed

Bitschar, Katharina; Wolz, Christiane; Krismer, Bernhard; Peschel, Andreas; Schittek, Birgit

2017-09-01

Healthy human skin provides an effective mechanical as well as immunologic barrier against pathogenic microorganisms with keratinocytes as the main cell type in the epidermis actively participating and orchestrating the innate immune response of the skin. As constituent of the outermost layer encountering potential pathogens they have to sense signals from the environment and must be able to initiate a differential immune response to harmless commensals and harmful pathogens. Staphylococci are among the most abundant colonizers of the skin: Whereas Staphylococcus epidermidis is part of the skin microbiota and ubiquitously colonizes human skin, Staphylococcus aureus is only rarely found on healthy human skin, but frequently colonizes the skin of atopic dermatitis (AD) patients. This review highlights recent advances in understanding how keratinocytes as sessile innate immune cells orchestrate an effective defense against S. aureus in healthy skin and the mechanisms leading to an impaired keratinocyte function in AD patients. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

An incoherent regulatory network architecture that orchestrates B cell diversification in response to antigen signaling

PubMed Central

Sciammas, Roger; Li, Ying; Warmflash, Aryeh; Song, Yiqiang; Dinner, Aaron R; Singh, Harinder

2011-01-01

The B-lymphocyte lineage is a leading system for analyzing gene regulatory networks (GRNs) that orchestrate distinct cell fate transitions. Upon antigen recognition, B cells can diversify their immunoglobulin (Ig) repertoire via somatic hypermutation (SHM) and/or class switch DNA recombination (CSR) before differentiating into antibody-secreting plasma cells. We construct a mathematical model for a GRN underlying this developmental dynamic. The intensity of signaling through the Ig receptor is shown to control the bimodal expression of a pivotal transcription factor, IRF-4, which dictates B cell fate outcomes. Computational modeling coupled with experimental analysis supports a model of ‘kinetic control', in which B cell developmental trajectories pass through an obligate transient state of variable duration that promotes diversification of the antibody repertoire by SHM/CSR in direct response to antigens. More generally, this network motif could be used to translate a morphogen gradient into developmental inductive events of varying time, thereby enabling the specification of distinct cell fates. PMID:21613984

De-optical-line-terminal hybrid access-aggregation optical network for time-sensitive services based on software-defined networking orchestration

NASA Astrophysics Data System (ADS)

Bai, Wei; Yang, Hui; Xiao, Hongyun; Yu, Ao; He, Linkuan; Zhang, Jie; Li, Zhen; Du, Yi

2017-11-01

With the increase in varieties of services in network, time-sensitive services (TSSs) appear and bring forward an impending need for delay performance. Ultralow-latency communication has become one of the important development goals for many scenarios in the coming 5G era (e.g., robotics and driverless cars). However, the conventional methods, which decrease delay by promoting the available resources and the network transmission speed, have limited effect; a new breakthrough for ultralow-latency communication is necessary. We propose a de-optical-line-terminal (De-OLT) hybrid access-aggregation optical network (DAON) for TSS based on software-defined networking (SDN) orchestration. In this network, low-latency all-optical communication based on optical burst switching can be achieved by removing OLT. For supporting this network and guaranteeing the quality of service for TSSs, we design SDN-driven control method and service provision method. Numerical results demonstrate the proposed DAON promotes network service efficiency and avoids traffic congestion.

Clique of Functional Hubs Orchestrates Population Bursts in Developmentally Regulated Neural Networks

PubMed Central

Luccioli, Stefano; Ben-Jacob, Eshel; Barzilai, Ari; Bonifazi, Paolo; Torcini, Alessandro

2014-01-01

It has recently been discovered that single neuron stimulation can impact network dynamics in immature and adult neuronal circuits. Here we report a novel mechanism which can explain in neuronal circuits, at an early stage of development, the peculiar role played by a few specific neurons in promoting/arresting the population activity. For this purpose, we consider a standard neuronal network model, with short-term synaptic plasticity, whose population activity is characterized by bursting behavior. The addition of developmentally inspired constraints and correlations in the distribution of the neuronal connectivities and excitabilities leads to the emergence of functional hub neurons, whose stimulation/deletion is critical for the network activity. Functional hubs form a clique, where a precise sequential activation of the neurons is essential to ignite collective events without any need for a specific topological architecture. Unsupervised time-lagged firings of supra-threshold cells, in connection with coordinated entrainments of near-threshold neurons, are the key ingredients to orchestrate population activity. PMID:25255443

Exosomes derived from human amniotic epithelial cells accelerate wound healing and inhibit scar formation.

PubMed

Zhao, Bin; Zhang, Yijie; Han, Shichao; Zhang, Wei; Zhou, Qin; Guan, Hao; Liu, Jiaqi; Shi, Jihong; Su, Linlin; Hu, Dahai

2017-04-01

Wound healing is a highly orchestrated physiological process consisting of a complex events, and scarless wound healing is highly desired for the development and application in clinical medicine. Recently, we have demonstrated that human amniotic epithelial cells (hAECs) promoted wound healing and inhibited scar formation through a paracrine mechanism. However, exosomes (Exo) are one of the most important paracrine factors. Whether exosomes derived from human amniotic epithelial cells (hAECs-Exo) have positive effects on scarless wound healing have not been reported yet. In this study, we examined the role of hAECs-Exo on wound healing in a rat model. We found that hAECs, which exhibit characteristics of both embryonic and mesenchymal stem cells, have the potential to differentiate into all three germ layers. hAECs-Exo ranged from 50 to 150 nm in diameter, and positive for exosomal markers CD9, CD63, CD81, Alix, TSG101 and HLA-G. Internalization of hAECs-Exo promoted the migration and proliferation of fibroblasts. Moreover, the deposition of extracellular matrix (ECM) were partly abolished by the treatment of high concentration of hAECs-Exo (100 μg/mL), which may be through stimulating the expression of matrix metalloproteinase-1 (MMP-1). In vivo animal experiments showed that hAECs-Exo improved the skin wound healing with well-organized collagen fibers. Taken together, These findings represent that hAECs-Exo can be used as a novel hope in cell-free therapy for scarless wound healing.

High Stimulus-Related Information in Barrel Cortex Inhibitory Interneurons

PubMed Central

Reyes-Puerta, Vicente; Kim, Suam; Sun, Jyh-Jang; Imbrosci, Barbara; Kilb, Werner; Luhmann, Heiko J.

2015-01-01

The manner in which populations of inhibitory (INH) and excitatory (EXC) neocortical neurons collectively encode stimulus-related information is a fundamental, yet still unresolved question. Here we address this question by simultaneously recording with large-scale multi-electrode arrays (of up to 128 channels) the activity of cell ensembles (of up to 74 neurons) distributed along all layers of 3–4 neighboring cortical columns in the anesthetized adult rat somatosensory barrel cortex in vivo. Using two different whisker stimulus modalities (location and frequency) we show that individual INH neurons – classified as such according to their distinct extracellular spike waveforms – discriminate better between restricted sets of stimuli (≤6 stimulus classes) than EXC neurons in granular and infra-granular layers. We also demonstrate that ensembles of INH cells jointly provide as much information about such stimuli as comparable ensembles containing the ~20% most informative EXC neurons, however presenting less information redundancy – a result which was consistent when applying both theoretical information measurements and linear discriminant analysis classifiers. These results suggest that a consortium of INH neurons dominates the information conveyed to the neocortical network, thereby efficiently processing incoming sensory activity. This conclusion extends our view on the role of the inhibitory system to orchestrate cortical activity. PMID:26098109

Ca2+ transport and signalling in enamel cells.

PubMed

Nurbaeva, Meerim K; Eckstein, Miriam; Feske, Stefan; Lacruz, Rodrigo S

2017-05-15

Dental enamel is one of the most remarkable examples of matrix-mediated biomineralization. Enamel crystals form de novo in a rich extracellular environment in a stage-dependent manner producing complex microstructural patterns that are visually stunning. This process is orchestrated by specialized epithelial cells known as ameloblasts which themselves undergo striking morphological changes, switching function from a secretory role to a cell primarily engaged in ionic transport. Ameloblasts are supported by a host of cell types which combined represent the enamel organ. Fully mineralized enamel is the hardest tissue found in vertebrates owing its properties partly to the unique mixture of ionic species represented and their highly organized assembly in the crystal lattice. Among the main elements found in enamel, Ca 2+ is the most abundant ion, yet how ameloblasts modulate Ca 2+ dynamics remains poorly known. This review describes previously proposed models for passive and active Ca 2+ transport, the intracellular Ca 2+ buffering systems expressed in ameloblasts and provides an up-dated view of current models concerning Ca 2+ influx and extrusion mechanisms, where most of the recent advances have been made. We also advance a new model for Ca 2+ transport by the enamel organ. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

SARS-CoV fusion peptides induce membrane surface ordering and curvature

PubMed Central

Basso, Luis G. M.; Vicente, Eduardo F.; Crusca Jr., Edson; Cilli, Eduardo M.; Costa-Filho, Antonio J.

2016-01-01

Viral membrane fusion is an orchestrated process triggered by membrane-anchored viral fusion glycoproteins. The S2 subunit of the spike glycoprotein from severe acute respiratory syndrome (SARS) coronavirus (CoV) contains internal domains called fusion peptides (FP) that play essential roles in virus entry. Although membrane fusion has been broadly studied, there are still major gaps in the molecular details of lipid rearrangements in the bilayer during fusion peptide-membrane interactions. Here we employed differential scanning calorimetry (DSC) and electron spin resonance (ESR) to gather information on the membrane fusion mechanism promoted by two putative SARS FPs. DSC data showed the peptides strongly perturb the structural integrity of anionic vesicles and support the hypothesis that the peptides generate opposing curvature stresses on phosphatidylethanolamine membranes. ESR showed that both FPs increase lipid packing and head group ordering as well as reduce the intramembrane water content for anionic membranes. Therefore, bending moment in the bilayer could be generated, promoting negative curvature. The significance of the ordering effect, membrane dehydration, changes in the curvature properties and the possible role of negatively charged phospholipids in helping to overcome the high kinetic barrier involved in the different stages of the SARS-CoV-mediated membrane fusion are discussed. PMID:27892522

Chemokine interactome mapping enables tailored intervention in acute and chronic inflammation.

PubMed

von Hundelshausen, Philipp; Agten, Stijn M; Eckardt, Veit; Blanchet, Xavier; Schmitt, Martin M; Ippel, Hans; Neideck, Carlos; Bidzhekov, Kiril; Leberzammer, Julian; Wichapong, Kanin; Faussner, Alexander; Drechsler, Maik; Grommes, Jochen; van Geffen, Johanna P; Li, He; Ortega-Gomez, Almudena; Megens, Remco T A; Naumann, Ronald; Dijkgraaf, Ingrid; Nicolaes, Gerry A F; Döring, Yvonne; Soehnlein, Oliver; Lutgens, Esther; Heemskerk, Johan W M; Koenen, Rory R; Mayo, Kevin H; Hackeng, Tilman M; Weber, Christian

2017-04-05

Chemokines orchestrate leukocyte trafficking and function in health and disease. Heterophilic interactions between chemokines in a given microenvironment may amplify, inhibit, or modulate their activity; however, a systematic evaluation of the chemokine interactome has not been performed. We used immunoligand blotting and surface plasmon resonance to obtain a comprehensive map of chemokine-chemokine interactions and to confirm their specificity. Structure-function analyses revealed that chemokine activity can be enhanced by CC-type heterodimers but inhibited by CXC-type heterodimers. Functional synergism was achieved through receptor heteromerization induced by CCL5-CCL17 or receptor retention at the cell surface via auxiliary proteoglycan binding of CCL5-CXCL4. In contrast, inhibitory activity relied on conformational changes (in CXCL12), affecting receptor signaling. Obligate CC-type heterodimers showed high efficacy and potency and drove acute lung injury and atherosclerosis, processes abrogated by specific CCL5-derived peptide inhibitors or knock-in of an interaction-deficient CXCL4 variant. Atheroprotective effects of CCL17 deficiency were phenocopied by a CCL5-derived peptide disrupting CCL5-CCL17 heterodimers, whereas a CCL5 α-helix peptide mimicked inhibitory effects on CXCL12-driven platelet aggregation. Thus, formation of specific chemokine heterodimers differentially dictates functional activity and can be exploited for therapeutic targeting. Copyright © 2017, American Association for the Advancement of Science.

20170312 - In Silico Dynamics: computer simulation in a ...

EPA Pesticide Factsheets

Abstract: Utilizing cell biological information to predict higher order biological processes is a significant challenge in predictive toxicology. This is especially true for highly dynamical systems such as the embryo where morphogenesis, growth and differentiation require precisely orchestrated interactions between diverse cell populations. In patterning the embryo, genetic signals setup spatial information that cells then translate into a coordinated biological response. This can be modeled as ‘biowiring diagrams’ representing genetic signals and responses. Because the hallmark of multicellular organization resides in the ability of cells to interact with one another via well-conserved signaling pathways, multiscale computational (in silico) models that enable these interactions provide a platform to translate cellular-molecular lesions perturbations into higher order predictions. Just as ‘the Cell’ is the fundamental unit of biology so too should it be the computational unit (‘Agent’) for modeling embryogenesis. As such, we constructed multicellular agent-based models (ABM) with ‘CompuCell3D’ (www.compucell3d.org) to simulate kinematics of complex cell signaling networks and enable critical tissue events for use in predictive toxicology. Seeding the ABMs with HTS/HCS data from ToxCast demonstrated the potential to predict, quantitatively, the higher order impacts of chemical disruption at the cellular or bioche

In Silico Dynamics: computer simulation in a Virtual Embryo ...

EPA Pesticide Factsheets

Abstract: Utilizing cell biological information to predict higher order biological processes is a significant challenge in predictive toxicology. This is especially true for highly dynamical systems such as the embryo where morphogenesis, growth and differentiation require precisely orchestrated interactions between diverse cell populations. In patterning the embryo, genetic signals setup spatial information that cells then translate into a coordinated biological response. This can be modeled as ‘biowiring diagrams’ representing genetic signals and responses. Because the hallmark of multicellular organization resides in the ability of cells to interact with one another via well-conserved signaling pathways, multiscale computational (in silico) models that enable these interactions provide a platform to translate cellular-molecular lesions perturbations into higher order predictions. Just as ‘the Cell’ is the fundamental unit of biology so too should it be the computational unit (‘Agent’) for modeling embryogenesis. As such, we constructed multicellular agent-based models (ABM) with ‘CompuCell3D’ (www.compucell3d.org) to simulate kinematics of complex cell signaling networks and enable critical tissue events for use in predictive toxicology. Seeding the ABMs with HTS/HCS data from ToxCast demonstrated the potential to predict, quantitatively, the higher order impacts of chemical disruption at the cellular or biochemical level. This is demonstrate

Lunar Plant Biology - A Review of the Apollo Era

NASA Astrophysics Data System (ADS)

Ferl, Robert J.; Paul, Anna-Lisa

2010-04-01

Recent plans for human return to the Moon have significantly elevated scientific interest in the lunar environment with emphasis on the science to be done in preparation for the return and while on the lunar surface. Since the return to the Moon is envisioned as a dedicated and potentially longer-term commitment to lunar exploration, questions of the lunar environment and particularly its impact on biology and biological systems have become a significant part of the lunar science discussion. Plants are integral to the discussion of biology on the Moon. Plants are envisioned as important components of advanced habitats and fundamental components of advanced life-support systems. Moreover, plants are sophisticated multicellular eukaryotic life-forms with highly orchestrated developmental processes, well-characterized signal transduction pathways, and exceedingly fine-tuned responses to their environments. Therefore, plants represent key test organisms for understanding the biological impact of the lunar environment on terrestrial life-forms. Indeed, plants were among the initial and primary organisms that were exposed to returned lunar regolith from the Apollo lunar missions. This review discusses the original experiments involving plants in association with the Apollo samples, with the intent of understanding those studies within the context of the first lunar exploration program and drawing from those experiments the data to inform the studies critical within the next lunar exploration science agenda.

Coping with Stresses: Roles of Calcium- and Calcium/Calmodulin-Regulated Gene Expression[W][OA

PubMed Central

Reddy, Anireddy S.N.; Ali, Gul S.; Celesnik, Helena; Day, Irene S.

2011-01-01

Abiotic and biotic stresses are major limiting factors of crop yields and cause billions of dollars of losses annually around the world. It is hoped that understanding at the molecular level how plants respond to adverse conditions and adapt to a changing environment will help in developing plants that can better cope with stresses. Acquisition of stress tolerance requires orchestration of a multitude of biochemical and physiological changes, and most of these depend on changes in gene expression. Research during the last two decades has established that different stresses cause signal-specific changes in cellular Ca2+ level, which functions as a messenger in modulating diverse physiological processes that are important for stress adaptation. In recent years, many Ca2+ and Ca2+/calmodulin (CaM) binding transcription factors (TFs) have been identified in plants. Functional analyses of some of these TFs indicate that they play key roles in stress signaling pathways. Here, we review recent progress in this area with emphasis on the roles of Ca2+- and Ca2+/CaM-regulated transcription in stress responses. We will discuss emerging paradigms in the field, highlight the areas that need further investigation, and present some promising novel high-throughput tools to address Ca2+-regulated transcriptional networks. PMID:21642548

Molecular cloning and structural characterization of Ecdysis Triggering Hormone from Choristoneura fumiferana.

PubMed

P, Bhagath Kumar; K, Kasi Viswanath; S, Tuleshwori Devi; R, Sampath Kumar; Doucet, Daniel; Retnakaran, Arthur; Krell, Peter J; Feng, Qili; Ampasala, Dinakara Rao

2016-07-01

At the end of each stadium, insects undergo a precisely orchestrated process known as ecdysis which results in the replacement of the old cuticle with a new one. This physiological event is necessary to accommodate growth in arthropods since they have a rigid chitinous exoskeleton. Ecdysis is initiated by the direct action of Ecdysis Triggering Hormones on the central nervous system. Choristoneura fumiferana is a major defoliator of coniferous forests in Eastern North America. It is assumed that, studies on the ecdysis behavior of this pest might lead to the development of novel pest management strategies. Hence in this study, the cDNA of CfETH was cloned. The open reading frame of the cDNA sequence was found to encode three putative peptides viz., Pre-Ecdysis Triggering Hormone (PETH), Ecdysis Triggering Hormone (ETH), and Ecdysis Triggering Hormone Associated Peptide (ETH-AP). The CfETH transcript was detected in the epidermal tissue of larval and pupal stages, but not in eggs and adults. In order to explore the structural conformation of ETH, ab initio modelling and Molecular Dynamics (MD) Simulations were performed. Further, a library of insecticides was generated and virtual screening was performed to identify the compounds displaying high binding capacity to ETH. Copyright © 2016 Elsevier B.V. All rights reserved.

Lunar plant biology--a review of the Apollo era.

PubMed

Ferl, Robert J; Paul, Anna-Lisa

2010-04-01

Recent plans for human return to the Moon have significantly elevated scientific interest in the lunar environment with emphasis on the science to be done in preparation for the return and while on the lunar surface. Since the return to the Moon is envisioned as a dedicated and potentially longer-term commitment to lunar exploration, questions of the lunar environment and particularly its impact on biology and biological systems have become a significant part of the lunar science discussion. Plants are integral to the discussion of biology on the Moon. Plants are envisioned as important components of advanced habitats and fundamental components of advanced life-support systems. Moreover, plants are sophisticated multicellular eukaryotic life-forms with highly orchestrated developmental processes, well-characterized signal transduction pathways, and exceedingly fine-tuned responses to their environments. Therefore, plants represent key test organisms for understanding the biological impact of the lunar environment on terrestrial life-forms. Indeed, plants were among the initial and primary organisms that were exposed to returned lunar regolith from the Apollo lunar missions. This review discusses the original experiments involving plants in association with the Apollo samples, with the intent of understanding those studies within the context of the first lunar exploration program and drawing from those experiments the data to inform the studies critical within the next lunar exploration science agenda.

Human amniotic epithelial stem cells promote wound healing by facilitating migration and proliferation of keratinocytes via ERK, JNK and AKT signaling pathways.

PubMed

Zhao, Bin; Liu, Jia-Qi; Zheng, Zhao; Zhang, Jun; Wang, Shu-Yue; Han, Shi-Chao; Zhou, Qin; Guan, Hao; Li, Chao; Su, Lin-Lin; Hu, Da-Hai

2016-07-01

Wound healing is a highly orchestrated physiological process consisting in a complex interaction of cellular and biochemical events. Human amniotic epithelial stem cells (HAESCs) have been shown to be an attractive resource for wound healing because they are primitive stem cells. However, the exact effects of amnion-derived stem cells on the migration or proliferation of keratinocytes and their potential mechanism are not fully understood. We have found that HAESCs accelerate the migration of keratinocytes and induce a remarkable increase in the activity of phospho-ERK, phospho-JNK, and phospho-AKT, the blockade of which by their specific inhibitors significantly inhibits migration induced by HAESC-conditioned medium (CM). Furthermore, the co-culture of keratinocytes with HAESCs up-regulates the expression levels of cell proliferation proteins Cyclin D1, Cyclin D3 and Mdm2. In vivo animal experiments have shown that HAESC-CM improves wound healing, whereas blockade with ERK, JNK and AKT inhibitors significantly impairs wound healing. Taken together, these results reveal, for the first time, that HAESCs promote wound healing by facilitating the migration and proliferation of keratinocytes via ERK, JNK and AKT signaling pathways and might be a potential therapy in skin wound healing.

Responds of Bone Cells to Microgravity: Ground-Based Research

NASA Astrophysics Data System (ADS)

Zhang, Jian; Li, Jingbao; Xu, Huiyun; Yang, Pengfei; Xie, Li; Qian, Airong; Zhao, Yong; Shang, Peng

2015-11-01

Severe loss of bone occurs due to long-duration spaceflight. Mechanical loading stimulates bone formation, while bone degradation happens under mechanical unloading. Bone remodeling is a dynamic process in which bone formation and bone resorption are tightly coupled. Increased bone resorption and decreased bone formation caused by reduced mechanical loading, generally result in disrupted bone remodeling. Bone remodeling is orchestrated by multiple bone cells including osteoblast, osteocyte, osteoclast and mesenchymal stem cell. It is yet not clear that how these bone cells sense altered gravity, translate physical stimulus into biochemical signals, and then regulate themselves structurally and functionally. In this paper, studies elucidating the bioeffects of microgravity on bone cells (osteoblast, osteocyte, osteoclast, mesenchymal stem cell) using various platforms including spaceflight and ground-based simulated microgravity were summarized. Promising gravity-sensitive signaling pathways and protein molecules were proposed.

Selective disruption of the AKAP signaling complexes.

PubMed

Kennedy, Eileen J; Scott, John D

2015-01-01

Synthesis of the second messenger cAMP activates a variety of signaling pathways critical for all facets of intracellular regulation. Protein kinase A (PKA) is the major cAMP-responsive effector. Where and when this enzyme is activated has profound implications on the cellular role of PKA. A-Kinase Anchoring Proteins (AKAPs) play a critical role in this process by orchestrating spatial and temporal aspects of PKA action. A popular means of evaluating the impact of these anchored signaling events is to biochemically interfere with the PKA-AKAP interface. Hence, peptide disruptors of PKA anchoring are valuable tools in the investigation of local PKA action. This article outlines the development of PKA isoform-selective disruptor peptides, documents the optimization of cell-soluble peptide derivatives, and introduces alternative cell-based approaches that interrogate other aspects of the PKA-AKAP interface.

Visualizing the complex functions and mechanisms of the anaphase promoting complex/cyclosome (APC/C)

PubMed Central

Alfieri, Claudio; Zhang, Suyang

2017-01-01

The anaphase promoting complex or cyclosome (APC/C) is a large multi-subunit E3 ubiquitin ligase that orchestrates cell cycle progression by mediating the degradation of important cell cycle regulators. During the two decades since its discovery, much has been learnt concerning its role in recognizing and ubiquitinating specific proteins in a cell-cycle-dependent manner, the mechanisms governing substrate specificity, the catalytic process of assembling polyubiquitin chains on its target proteins, and its regulation by phosphorylation and the spindle assembly checkpoint. The past few years have witnessed significant progress in understanding the quantitative mechanisms underlying these varied APC/C functions. This review integrates the overall functions and properties of the APC/C with mechanistic insights gained from recent cryo-electron microscopy (cryo-EM) studies of reconstituted human APC/C complexes. PMID:29167309

Nuclear Transcription Factors in the Mitochondria: A New Paradigm in Fine-Tuning Mitochondrial Metabolism.

PubMed

Sepuri, Naresh Babu V; Tammineni, Prasad; Mohammed, Fareed; Paripati, Arunkumar

2017-01-01

Noncanonical functions of several nuclear transcription factors in the mitochondria have been gaining exceptional traction over the years. These transcription factors include nuclear hormone receptors like estrogen, glucocorticoid, and thyroid hormone receptors: p53, IRF3, STAT3, STAT5, CREB, NF-kB, and MEF-2D. Mitochondria-localized nuclear transcription factors regulate mitochondrial processes like apoptosis, respiration and mitochondrial transcription albeit being nuclear in origin and having nuclear functions. Hence, the cell permits these multi-stationed transcription factors to orchestrate and fine-tune cellular metabolism at various levels of operation. Despite their ubiquitous distribution in different subcompartments of mitochondria, their targeting mechanism is poorly understood. Here, we review the current status of mitochondria-localized transcription factors and discuss the possible targeting mechanism besides the functional interplay between these factors.

Launching Complex Tasks

ERIC Educational Resources Information Center

Jackson, Kara J.; Shahan, Emily C.; Gibbons, Lynsey K.; Cobb, Paul A.

2012-01-01

Mathematics lessons can take a variety of formats. In this article, the authors discuss lessons organized around complex mathematical tasks. These lessons usually unfold in three phases. First, the task is introduced to students. Second, students work on solving the task. Third, the teacher "orchestrates" a concluding whole-class discussion in…

Orchestrating Mathematical Discourse: Affordances and Hindrances for Novice Elementary Teachers

ERIC Educational Resources Information Center

Lee, Carrie Wilkerson

2016-01-01

The purpose of this study was to examine the mathematical discourse within novice elementary teachers' classrooms. More specifically, this study employed a sequential, explanatory mixed methods design to first quantitatively analyze the relationship between teachers' discourse practices and teacher attributes and school context. Next, a…

Strengthening Discussions

ERIC Educational Resources Information Center

Hintz, Allison B.

2013-01-01

"Strategy sharing" is a certain type of discussion that centers on students' ideas and occurs when children present different approaches to problems and provide information about how they solved the problem (Wood, Williams, and McNeal 2004). A teacher may orchestrate a strategy-sharing discussion to achieve one or more of the…

The role of mitochondria in plant development and stress tolerance

USDA-ARS?s Scientific Manuscript database

Proper cellular function requires orchestrated communication among cellular compartments and the ability of the cell to sense and respond to its environment. Plant cells contain three distinct compartments that house DNA. The nucleus contains the nuclear genome, which provides a majority of a cell's...

View from 30,000 Feet

ERIC Educational Resources Information Center

Freifeld, Lorri

2012-01-01

Orchestrating a smooth training transition during a merger or acquisition is never easy. When Delta Air Lines absorbed Northwest Airlines Corp. in 2008, the Training function realized it was in for a bumpy ride. This article looks at the strategies used and progress made since the takeover was announced.

Supporting Secondary Novices' Efforts to Implement Student- and Discourse-Centred Pedagogical Practices

ERIC Educational Resources Information Center

Lewis, Gary

2012-01-01

Novice secondary mathematics teachers attempting teaching consonant with NCTM (1991) Professional Standards for Teaching Mathematics experience stresses related to those attempts. Foremost among those stresses are challenges while orchestrating student-centred, whole-class discussions. Such discussions can create uncertainty and stress as novices…

The allosteric HIV-1 integrase inhibitor BI-D affects virion maturation but does not influence packaging of a functional RNA genome.

PubMed

van Bel, Nikki; van der Velden, Yme; Bonnard, Damien; Le Rouzic, Erwann; Das, Atze T; Benarous, Richard; Berkhout, Ben

2014-01-01

The viral integrase (IN) is an essential protein for HIV-1 replication. IN inserts the viral dsDNA into the host chromosome, thereby aided by the cellular co-factor LEDGF/p75. Recently a new class of integrase inhibitors was described: allosteric IN inhibitors (ALLINIs). Although designed to interfere with the IN-LEDGF/p75 interaction to block HIV DNA integration during the early phase of HIV-1 replication, the major impact was surprisingly found on the process of virus maturation during the late phase, causing a reverse transcription defect upon infection of target cells. Virus particles produced in the presence of an ALLINI are misformed with the ribonucleoprotein located outside the virus core. Virus assembly and maturation are highly orchestrated and regulated processes in which several viral proteins and RNA molecules closely interact. It is therefore of interest to study whether ALLINIs have unpredicted pleiotropic effects on these RNA-related processes. We confirm that the ALLINI BI-D inhibits virus replication and that the produced virus is non-infectious. Furthermore, we show that the wild-type level of HIV-1 genomic RNA is packaged in virions and these genomes are in a dimeric state. The tRNAlys3 primer for reverse transcription was properly placed on this genomic RNA and could be extended ex vivo. In addition, the packaged reverse transcriptase enzyme was fully active when extracted from virions. As the RNA and enzyme components for reverse transcription are properly present in virions produced in the presence of BI-D, the inhibition of reverse transcription is likely to reflect the mislocalization of the components in the aberrant virus particle.

Structural Characterization by Cross-linking Reveals the Detailed Architecture of a Coatomer-related Heptameric Module from the Nuclear Pore Complex*

PubMed Central

Shi, Yi; Fernandez-Martinez, Javier; Tjioe, Elina; Pellarin, Riccardo; Kim, Seung Joong; Williams, Rosemary; Schneidman-Duhovny, Dina; Sali, Andrej; Rout, Michael P.; Chait, Brian T.

2014-01-01

Most cellular processes are orchestrated by macromolecular complexes. However, structural elucidation of these endogenous complexes can be challenging because they frequently contain large numbers of proteins, are compositionally and morphologically heterogeneous, can be dynamic, and are often of low abundance in the cell. Here, we present a strategy for the structural characterization of such complexes that has at its center chemical cross-linking with mass spectrometric readout. In this strategy, we isolate the endogenous complexes using a highly optimized sample preparation protocol and generate a comprehensive, high-quality cross-linking dataset using two complementary cross-linking reagents. We then determine the structure of the complex using a refined integrative method that combines the cross-linking data with information generated from other sources, including electron microscopy, X-ray crystallography, and comparative protein structure modeling. We applied this integrative strategy to determine the structure of the native Nup84 complex, a stable hetero-heptameric assembly (∼600 kDa), 16 copies of which form the outer rings of the 50-MDa nuclear pore complex (NPC) in budding yeast. The unprecedented detail of the Nup84 complex structure reveals previously unseen features in its pentameric structural hub and provides information on the conformational flexibility of the assembly. These additional details further support and augment the protocoatomer hypothesis, which proposes an evolutionary relationship between vesicle coating complexes and the NPC, and indicates a conserved mechanism by which the NPC is anchored in the nuclear envelope. PMID:25161197

Multiplexed multi-scale imaging: novel roles for the scaffold protein IQGAP1 in epithelial cell development (Conference Presentation)

NASA Astrophysics Data System (ADS)

Schweikhard, Volker

2016-02-01

The precise sub-cellular spatial localization of multi-protein complexes is increasingly recognized as a key mechanism governing the organization of mammalian cells. Consequently, there is a need for novel microscopy techniques capable of investigating such sub-cellular architectures in comprehensive detail. Here, we applied a novel multiplexed STORM super-resolution microscopy technique, in combination with high-throughput immunofluorescence microscopy and live-cell imaging, to investigate the roles of the scaffold protein IQGAP1 in epithelial cells. IQGAP1 is known to orchestrate a wide range of biological processes, including intracellular signaling, cytoskeletal regulation, cell-cell adhesion, and protein trafficking, by forming distinct complexes with a number of known interaction partners, and recruiting these complexes to specific subcellular locations. Our results demonstrate that, in addition to supporting epithelial adherens junctions by associating with specialized cortical actin structures, IQGAP1 plays a second role in which it controls the confinement of a unique, previously undocumented class of membranous compartments to the basal actin cortex. These largely immotile yet highly dynamic structures appear transiently as cells merge into clusters and establish of apical-basolateral (epithelial) polarity, and are identified as an intermediate compartment in the endocytic recycling pathways for cell junction complexes and cell surface receptors. Although these two functions of IQGAP1 occur in parallel and largely independently of each other, they both support the maturation and maintenance of polarized epithelial cell architectures.

Volitional regulation of brain responses to food stimuli in overweight and obese subjects: A real-time fMRI feedback study.

PubMed

Spetter, Maartje S; Malekshahi, Rahim; Birbaumer, Niels; Lührs, Michael; van der Veer, Albert H; Scheffler, Klaus; Spuckti, Sophia; Preissl, Hubert; Veit, Ralf; Hallschmid, Manfred

2017-05-01

Obese subjects who achieve weight loss show increased functional connectivity between dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC), key areas of executive control and reward processing. We investigated the potential of real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback training to achieve healthier food choices by enhancing self-control of the interplay between these brain areas. We trained eight male individuals with overweight or obesity (age: 31.8 ± 4.4 years, BMI: 29.4 ± 1.4 kg/m 2 ) to up-regulate functional connectivity between the dlPFC and the vmPFC by means of a four-day rt-fMRI neurofeedback protocol including, on each day, three training runs comprised of six up-regulation and six passive viewing trials. During the up-regulation runs of the four training days, participants successfully learned to increase functional connectivity between dlPFC and vmPFC. In addition, a trend towards less high-calorie food choices emerged from before to after training, which however was associated with a trend towards increased covertly assessed snack intake. Findings of this proof-of-concept study indicate that overweight and obese participants can increase functional connectivity between brain areas that orchestrate the top-down control of appetite for high-calorie foods. Neurofeedback training might therefore be a useful tool in achieving and maintaining weight loss. Copyright © 2017 Elsevier Ltd. All rights reserved.

Beliefs and practices of the parents of violent and oppositional adolescents: an ecological perspective.

PubMed

Bradshaw, Catherine P; Glaser, Brian A; Calhoun, Georgia B; Bates, Jeffrey M

2006-05-01

Parenting is a transactional process, influenced by the child's behavior and the environmental context. The present study explores the beliefs and practices of parents of aggressive and oppositional adolescents to understand better the relation among parenting practices, context, and youth violence. Parents of juvenile offenders (N=203) completed assessments of youths' violent and oppositional behaviors, community violence exposure, and their own beliefs and parenting behaviors and perceptions of the juvenile justice system. Parents of youth with the highest levels of violent and oppositional behavior problems reported elevated feelings of hopelessness regarding the child's future, inadequacy as a parent, fear of physical harm by the child, anger toward the child, as well as difficulty monitoring the child. All parents reported relatively high levels of perceived support by the justice system. Parental stress was also examined as a possible influence on the parents' beliefs and behaviors regarding the child. Results suggest that parents' emotional and behavioral responses should be addressed when intervening with juvenile offenders. Editors' Strategic Implications: The authors present evidence to suggest that parents' perceptions of hopelessness/inadequacy and their fear for their child's safety are both by-products of life with an aggressive child as well as contributing factors to that aggressive behavior. Thus, successful interventions must both target the parents as change agents in the youth's life but also include a strong parental support component, so that parents will have an opportunity to orchestrate positive impacts in high-risk environments.

Coupling of a continuum ice sheet model and a discrete element calving model using a scientific workflow system

NASA Astrophysics Data System (ADS)

Memon, Shahbaz; Vallot, Dorothée; Zwinger, Thomas; Neukirchen, Helmut

2017-04-01

Scientific communities generate complex simulations through orchestration of semi-structured analysis pipelines which involves execution of large workflows on multiple, distributed and heterogeneous computing and data resources. Modeling ice dynamics of glaciers requires workflows consisting of many non-trivial, computationally expensive processing tasks which are coupled to each other. From this domain, we present an e-Science use case, a workflow, which requires the execution of a continuum ice flow model and a discrete element based calving model in an iterative manner. Apart from the execution, this workflow also contains data format conversion tasks that support the execution of ice flow and calving by means of transition through sequential, nested and iterative steps. Thus, the management and monitoring of all the processing tasks including data management and transfer of the workflow model becomes more complex. From the implementation perspective, this workflow model was initially developed on a set of scripts using static data input and output references. In the course of application usage when more scripts or modifications introduced as per user requirements, the debugging and validation of results were more cumbersome to achieve. To address these problems, we identified a need to have a high-level scientific workflow tool through which all the above mentioned processes can be achieved in an efficient and usable manner. We decided to make use of the e-Science middleware UNICORE (Uniform Interface to Computing Resources) that allows seamless and automated access to different heterogenous and distributed resources which is supported by a scientific workflow engine. Based on this, we developed a high-level scientific workflow model for coupling of massively parallel High-Performance Computing (HPC) jobs: a continuum ice sheet model (Elmer/Ice) and a discrete element calving and crevassing model (HiDEM). In our talk we present how the use of a high-level scientific workflow middleware enables reproducibility of results more convenient and also provides a reusable and portable workflow template that can be deployed across different computing infrastructures. Acknowledgements This work was kindly supported by NordForsk as part of the Nordic Center of Excellence (NCoE) eSTICC (eScience Tools for Investigating Climate Change at High Northern Latitudes) and the Top-level Research Initiative NCoE SVALI (Stability and Variation of Arctic Land Ice).

Microtubules move the nucleus to quiescence.

PubMed

Laporte, Damien; Sagot, Isabelle

2014-01-01

The nucleus is a cellular compartment that hosts several macro-molecular machines displaying a highly complex spatial organization. This tight architectural orchestration determines not only DNA replication and repair but also regulates gene expression. In budding yeast microtubules play a key role in structuring the nucleus since they condition the Rabl arrangement in G1 and chromosome partitioning during mitosis through their attachment to centromeres via the kinetochore proteins. Recently, we have shown that upon quiescence entry, intranuclear microtubules emanating from the spindle pole body elongate to form a highly stable bundle that spans the entire nucleus. Here, we examine some molecular mechanisms that may underlie the formation of this structure. As the intranuclear microtubule bundle causes a profound re-organization of the yeast nucleus and is required for cell survival during quiescence, we discuss the possibility that the assembly of such a structure participates in quiescence establishment.

Hormetic Response to Low-Dose Radiation: Focus on the Immune System and Its Clinical Implications

PubMed Central

Cui, Jiuwei; Yang, Guozi; Pan, Zhenyu; Zhao, Yuguang; Liang, Xinyue; Li, Wei; Cai, Lu

2017-01-01

The interrelationship between ionizing radiation and the immune system is complex, multifactorial, and dependent on radiation dose/quality and immune cell type. High-dose radiation usually results in immune suppression. On the contrary, low-dose radiation (LDR) modulates a variety of immune responses that have exhibited the properties of immune hormesis. Although the underlying molecular mechanism is not fully understood yet, LDR has been used clinically for the treatment of autoimmune diseases and malignant tumors. These advancements in preclinical and clinical studies suggest that LDR-mediated immune modulation is a well-orchestrated phenomenon with clinical potential. We summarize recent developments in the understanding of LDR-mediated immune modulation, with an emphasis on its potential clinical applications. PMID:28134809

Natural Immunity to HIV: a delicate balance between strength and control.

PubMed

Poudrier, Johanne; Thibodeau, Valérie; Roger, Michel

2012-01-01

Understanding how the mucosal immune system in the human female reproductive tract might prevent or facilitate HIV infection has important implications for the design of effective interventions. We and others have established cohorts of highly-exposed, HIV-seronegative individuals, such as HIV-uninfected commercial sex workers, who have remained HIV-negative after more than 5 years of active prostitution. Observations obtained in studies of such individuals, who represent a model of natural immunity to HIV, indicate that HIV resistance may be associated with the host's capacity to preserve systemic integrity by constraining immune activity and controlling inflammatory conditions at the mucosal point of entry. This likely necessitates the orchestration of balanced, first-line and adaptive immune responses.

Complex pectin metabolism by gut bacteria reveals novel catalytic functions

PubMed Central

Baslé, Arnaud; Gray, Joseph; Venditto, Immacolata; Briggs, Jonathon; Zhang, Xiaoyang; Labourel, Aurore; Terrapon, Nicolas; Buffetto, Fanny; Nepogodiev, Sergey; Xiao, Yao; Field, Robert A.; Zhu, Yanping; O’Neil, Malcolm A.; Urbanowicz, Breeana R.; York, William S.; Davies, Gideon J.; Abbott, D. Wade; Ralet, Marie-Christine; Martens, Eric C.; Henrissat, Bernard; Gilbert, Harry J.

2017-01-01

Carbohydrate polymers drive microbial diversity in the human gut microbiota. It is unclear, however, whether bacterial consortia or single organisms are required to depolymerize highly complex glycans. Here we show that the gut bacterium Bacteroides thetaiotaomicron utilizes the most structurally complex glycan known; the plant pectic polysaccharide rhamnogalacturonan-II, cleaving all but one of its 21 distinct glycosidic linkages. We show that rhamnogalacturonan-II side-chain and backbone deconstruction are coordinated, to overcome steric constraints, and that degradation reveals previously undiscovered enzyme families and novel catalytic activities. The degradome informs revision of the current structural model of RG-II and highlights how individual gut bacteria orchestrate manifold enzymes to metabolize the most challenging glycans in the human diet. PMID:28329766

The Big Picture: An Overview

ERIC Educational Resources Information Center

Hom, Willard C.

2010-01-01

The system office for community college institutional research (SOCCIR) plays a role in the drama of higher education that states must orchestrate to help community college systems operate effectively and efficiently over the long term. But how exactly does the SOCCIR enable a state to accomplish what the separate institutional research (IR)…

Orchestrating Authorship: Teaching Writing across the Psychology Curriculum

ERIC Educational Resources Information Center

Soysa, Champika K.; Dunn, Dana S.; Dottolo, Andrea L.; Burns-Glover, Alyson L.; Gurung, Regan A. R.

2013-01-01

This article describes the kinds of writing that could be introduced at the beginner, intermediate, and advanced course levels in the psychology major. We present exemplars of writing assignments across three institutions, including textual analysis, integrating intratext and intertext writing, and a capstone thesis project, where the skills…

Interactive Whiteboards and All That Jazz: Analysing Classroom Activity with Interactive Technologies

ERIC Educational Resources Information Center

Tanner, Howard; Beauchamp, Gary; Jones, Sonia; Kennewell, Steve

2010-01-01

The term "orchestration", has been used to describe the teacher's role in activity settings incorporating interactive technologies. This musical analogy suggests pre-planned manipulation of events to generate "performance" leading to learning. However, in two recent projects we have observed how effective teaching and learning…

Music: Instrumental Techniques, Strings.

ERIC Educational Resources Information Center

Ryan, Philip

A course in music which emphasizes harmony is presented. The approach used is a laboratory one in which pupils will develop skill in playing orchestral string instruments, sing, listen to, read and compose music with emphasis on elementary concepts of harmony. Course objectives include: (1) The student will select the title of a familiar melody…

Orchestrating Literacies: Print Literacy Learning Opportunities within Multimodal Intergenerational Ensembles

ERIC Educational Resources Information Center

McKee, Lori L.; Heydon, Rachel M.

2015-01-01

This exploratory case study considered the opportunities for print literacy learning within multimodal ensembles that featured art, singing and digital media within the context of an intergenerational programme that brought together 13 kindergarten children (4 and 5 years) with seven elder companions. Study questions concerned how reading and…

Educating Orchestral Musicians

ERIC Educational Resources Information Center

Calissendorff, Maria; Hannesson, Haukur F.

2017-01-01

This article examines research on the specific training of musicians before they begin work as players in professional orchestras. Most of the research is in the area of education. The present article suggests that little research exists that is specific to the development of a traditional orchestra musician from an early age through the music…

Settling the 'Score' with Heart Disease

NASA Technical Reports Server (NTRS)

2004-01-01

Technology and medicine forged a bond in 1986 when a group of dedicated NASA scientists, University of Southern California (USC) medical professors, and a Dutch cardiologist joined forces to prevent heart attacks, using ultrasound images of astronauts blood-flow patterns and the supercomputer depended upon to orchestrate the "Star Wars" Strategic Defense Initiative.