Comprehensive Characterization of Minichromosome Maintenance Complex (MCM) Protein Interactions Using Affinity and Proximity Purifications Coupled to Mass Spectrometry.

PubMed

Dubois, Marie-Line; Bastin, Charlotte; Lévesque, Dominique; Boisvert, François-Michel

2016-09-02

The extensive identification of protein-protein interactions under different conditions is an important challenge to understand the cellular functions of proteins. Here we use and compare different approaches including affinity purification and purification by proximity coupled to mass spectrometry to identify protein complexes. We explore the complete interactome of the minichromosome maintenance (MCM) complex by using both approaches for all of the different MCM proteins. Overall, our analysis identified unique and shared interaction partners and proteins enriched for distinct biological processes including DNA replication, DNA repair, and cell cycle regulation. Furthermore, we mapped the changes in protein interactions of the MCM complex in response to DNA damage, identifying a new role for this complex in DNA repair. In summary, we demonstrate the complementarity of these approaches for the characterization of protein interactions within the MCM complex.

Coevolution study of mitochondria respiratory chain proteins: toward the understanding of protein--protein interaction.

PubMed

Yang, Ming; Ge, Yan; Wu, Jiayan; Xiao, Jingfa; Yu, Jun

2011-05-20

Coevolution can be seen as the interdependency between evolutionary histories. In the context of protein evolution, functional correlation proteins are ever-present coordinated evolutionary characters without disruption of organismal integrity. As to complex system, there are two forms of protein--protein interactions in vivo, which refer to inter-complex interaction and intra-complex interaction. In this paper, we studied the difference of coevolution characters between inter-complex interaction and intra-complex interaction using "Mirror tree" method on the respiratory chain (RC) proteins. We divided the correlation coefficients of every pairwise RC proteins into two groups corresponding to the binary protein--protein interaction in intra-complex and the binary protein--protein interaction in inter-complex, respectively. A dramatical discrepancy is detected between the coevolution characters of the two sets of protein interactions (Wilcoxon test, p-value = 4.4 × 10(-6)). Our finding reveals some critical information on coevolutionary study and assists the mechanical investigation of protein--protein interaction. Furthermore, the results also provide some unique clue for supramolecular organization of protein complexes in the mitochondrial inner membrane. More detailed binding sites map and genome information of nuclear encoded RC proteins will be extraordinary valuable for the further mitochondria dynamics study. Copyright © 2011. Published by Elsevier Ltd.

Analysis of context dependence in social interaction networks of a massively multiplayer online role-playing game.

PubMed

Son, Seokshin; Kang, Ah Reum; Kim, Hyun-chul; Kwon, Taekyoung; Park, Juyong; Kim, Huy Kang

2012-01-01

Rapid advances in modern computing and information technology have enabled millions of people to interact online via various social network and gaming services. The widespread adoption of such online services have made possible analysis of large-scale archival data containing detailed human interactions, presenting a very promising opportunity to understand the rich and complex human behavior. In collaboration with a leading global provider of Massively Multiplayer Online Role-Playing Games (MMORPGs), here we present a network science-based analysis of the interplay between distinct types of user interaction networks in the virtual world. We find that their properties depend critically on the nature of the context-interdependence of the interactions, highlighting the complex and multilayered nature of human interactions, a robust understanding of which we believe may prove instrumental in the designing of more realistic future virtual arenas as well as provide novel insights to the science of collective human behavior.

Spectroscopic investigations of the charge-transfer interaction between the drug reserpine and different acceptors: Towards understanding of drug-receptor mechanism

NASA Astrophysics Data System (ADS)

Eldaroti, Hala H.; Gadir, Suad A.; Refat, Moamen S.; Adam, Abdel Majid A.

2013-11-01

The study of the charge-transfer interaction of the drugs may be useful in understanding the drug-receptor interactions and the mechanism of drug action. Structural and thermal stability of charge-transfer (CT) complexes formed between the drug reserpine (Res) as a donor and quinol (QL), picric acid (PA), tetracyanoquinodimethane (TCNQ) or dichlorodicyanobenzoquinone (DDQ) as acceptors were reported. Elemental analysis, electronic absorption, spectrophotometric titration, IR, Raman, 1H NMR and X-ray powder diffraction (XRD) were used to characterize the new products. The thermal stability of the synthesized CT complexes was investigated using thermogravimetric (TG) analyses, and the morphology and particle size of these complexes were obtained from scanning electron microscopy (SEM). The stoichiometry of the complexes (donor:acceptor molar ratio) was determined to be 1:1 for all complexes. Accordingly the formed CT complexes could be formulated as [(Res)(QL)], [(Res)(PA)], [(Res)(TCNQ)] and [(Res)(DDQ)]. It was found that the obtained CT complexes are nanoscale, semi-crystalline particles, thermally stable and formed through spontaneous reaction. The results obtained herein are satisfactory for estimation of drug Res in the pharmaceutical form.

Coming to Understand Diversity and Education: Life Experiences and Educational Opportunities

ERIC Educational Resources Information Center

Chamberlain, Steven Paul

2015-01-01

Coming to understand how cultural differences influence interactions between educators and students and their parents is a complex and perhaps life-long discovery. Culture helps to define groups' belief systems and expectations for appropriate behavior, often at a hidden level. Pre-service teachers need multiple opportunities to interact with…

Understanding Protein Synthesis: An Interactive Card Game Discussion

ERIC Educational Resources Information Center

Lewis, Alison; Peat, Mary; Franklin, Sue

2005-01-01

Protein synthesis is a complex process and students find it difficult to understand. This article describes an interactive discussion "game" used by first year biology students at the University of Sydney. The students, in small groups, use the game in which the processes of protein synthesis are actioned by the students during a…

Dopamine D2 heteroreceptor complexes and their receptor-receptor interactions in ventral striatum: novel targets for antipsychotic drugs.

PubMed

Fuxe, Kjell; Borroto-Escuela, Dasiel O; Tarakanov, Alexander O; Romero-Fernandez, Wilber; Ferraro, Luca; Tanganelli, Sergio; Perez-Alea, Mileidys; Di Palma, Michael; Agnati, Luigi F

2014-01-01

This review is focused on the D2 heteroreceptor complexes within the ventral striatum with their receptor-receptor interactions and relevance for the treatment of schizophrenia. A "guide-and-clasp" manner for receptor-receptor interactions is proposed where "adhesive guides" may be amino acid triplet homologies, which were determined for different kinds of D2 heteroreceptor complexes. The first putative D2 heteroreceptor complex to be discovered in relation to schizophrenia was the A2A-D2 heteroreceptor complex where antagonistic A2A-D2 receptor-receptor interactions were demonstrated after A2A agonist treatment in the ventral striatum. The A2A agonist CGS 21680 with atypical antipsychotic properties may at least in part act by increasing β-arrestin2 signaling over the D2 protomer in the A2A-D2 heteroreceptor complex in the ventral striatum. The antagonistic NTS1-D2 interactions in the NTS1-D2 heteroreceptor complex in the ventral striatum are proposed as one molecular mechanism for the potential antipsychotic effects of NT. Indications were obtained that the psychotic actions of the 5-HT2AR hallucinogens LSD and DOI can involve enhancement of D2R protomer signaling via a biased agonist action at the 5-HT2A protomer in the D2-5-HT2A heteroreceptor complex in the ventral striatum. Facilitatory allosteric D2likeR-OTR interactions in heteroreceptor complexes in nucleus accumbens may have a role in social and emotional behaviors. By blocking the D2 protomers of these heteroreceptor complexes, antipsychotics can fail to reduce the negative symptoms of schizophrenia. The discovery of different types of D2 heteroreceptor complexes gives an increased understanding of molecular mechanisms involved in causing schizophrenia and new strategies for its treatment and understanding the side effects of antipsychotics. © 2014 Elsevier B.V. All rights reserved.

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.

Residue-residue contacts: application to analysis of secondary structure interactions.

PubMed

Potapov, Vladimir; Edelman, Marvin; Sobolev, Vladimir

2013-01-01

Protein structures and their complexes are formed and stabilized by interactions, both inside and outside of the protein. Analysis of such interactions helps in understanding different levels of structures (secondary, super-secondary, and oligomeric states). It can also assist molecular biologists in understanding structural consequences of modifying proteins and/or ligands. In this chapter, our definition of atom-atom and residue-residue contacts is described and applied to analysis of protein-protein interactions in dimeric β-sandwich proteins.

A review of human factors challenges of complex adaptive systems: discovering and understanding chaos in human performance.

PubMed

Karwowski, Waldemar

2012-12-01

In this paper, the author explores a need for a greater understanding of the true nature of human-system interactions from the perspective of the theory of complex adaptive systems, including the essence of complexity, emergent properties of system behavior, nonlinear systems dynamics, and deterministic chaos. Human performance, more often than not, constitutes complex adaptive phenomena with emergent properties that exhibit nonlinear dynamical (chaotic) behaviors. The complexity challenges in the design and management of contemporary work systems, including service systems, are explored. Examples of selected applications of the concepts of nonlinear dynamics to the study of human physical performance are provided. Understanding and applications of the concepts of theory of complex adaptive and dynamical systems should significantly improve the effectiveness of human-centered design efforts of a large system of systems. Performance of many contemporary work systems and environments may be sensitive to the initial conditions and may exhibit dynamic nonlinear properties and chaotic system behaviors. Human-centered design of emergent human-system interactions requires application of the theories of nonlinear dynamics and complex adaptive system. The success of future human-systems integration efforts requires the fusion of paradigms, knowledge, design principles, and methodologies of human factors and ergonomics with those of the science of complex adaptive systems as well as modern systems engineering.

Progress in the Analysis of Complex Atmospheric Particles.

PubMed

Laskin, Alexander; Gilles, Mary K; Knopf, Daniel A; Wang, Bingbing; China, Swarup

2016-06-12

This article presents an overview of recent advances in field and laboratory studies of atmospheric particles formed in processes of environmental air-surface interactions. The overarching goal of these studies is to advance predictive understanding of atmospheric particle composition, particle chemistry during aging, and their environmental impacts. The diversity between chemical constituents and lateral heterogeneity within individual particles adds to the chemical complexity of particles and their surfaces. Once emitted, particles undergo transformation via atmospheric aging processes that further modify their complex composition. We highlight a range of modern analytical approaches that enable multimodal chemical characterization of particles with both molecular and lateral specificity. When combined, these approaches provide a comprehensive arsenal of tools for understanding the nature of particles at air-surface interactions and their reactivity and transformations with atmospheric aging. We discuss applications of these novel approaches in recent studies and highlight additional research areas to explore the environmental effects of air-surface interactions.

Combining research approaches to advance our understanding of drug addiction.

PubMed

van den Bree, Marianne B M

2005-04-01

Drug addiction is a complex behavior, likely to be influenced by various genes, environmental factors, and gene-gene and gene-environment interactions. Various aspects of addiction are studied by different disciplines. Animal studies are increasing insight into brain regions and genes associated with addiction. Epidemiologic studies are establishing the factors increasing risk for initiation and continuation of substance use. Twin and adoption studies are increasing our understanding of the complex mechanisms involved in substance use, including comorbidity and gene environment interaction. Finally, molecular genetic studies in humans are starting to yield some converging findings. It is argued and illustrated with examples that greater awareness of progress in other disciplines can speed up our understanding of the complex processes involved in addiction. This should help our ability to identify who is at increased risk of becoming addicted and the development of prevention and intervention strategies targeted at an individual's specific needs.

Homeostatis and Complexity as Integrating Tools in Gerontological Education.

ERIC Educational Resources Information Center

Richardson, Daniel; McCulloch, B. Jan; Rowles, Graham D.

2001-01-01

A gerontology doctoral program used the concepts of homeostasis and complexity to present biomedical and psychosocial issues. Data from 14 students showed that homeostasis was more useful for biomedical than psychosocial issues. Complexity helped in understanding interactions between the two. (SK)

Synchronization in human musical rhythms and mutually interacting complex systems

PubMed Central

Hennig, Holger

2014-01-01

Though the music produced by an ensemble is influenced by multiple factors, including musical genre, musician skill, and individual interpretation, rhythmic synchronization is at the foundation of musical interaction. Here, we study the statistical nature of the mutual interaction between two humans synchronizing rhythms. We find that the interbeat intervals of both laypeople and professional musicians exhibit scale-free (power law) cross-correlations. Surprisingly, the next beat to be played by one person is dependent on the entire history of the other person’s interbeat intervals on timescales up to several minutes. To understand this finding, we propose a general stochastic model for mutually interacting complex systems, which suggests a physiologically motivated explanation for the occurrence of scale-free cross-correlations. We show that the observed long-term memory phenomenon in rhythmic synchronization can be imitated by fractal coupling of separately recorded or synthesized audio tracks and thus applied in electronic music. Though this study provides an understanding of fundamental characteristics of timing and synchronization at the interbrain level, the mutually interacting complex systems model may also be applied to study the dynamics of other complex systems where scale-free cross-correlations have been observed, including econophysics, physiological time series, and collective behavior of animal flocks. PMID:25114228

Biochemistry students' ideas about how an enzyme interacts with a substrate.

PubMed

Linenberger, Kimberly J; Bretz, Stacey Lowery

2015-01-01

Enzyme-substrate interactions are a fundamental concept of biochemistry that is built upon throughout multiple biochemistry courses. Central to understanding enzyme-substrate interactions is specific knowledge of exactly how an enzyme and substrate interact. Within this narrower topic, students must understand the various binding sites on an enzyme and be able to reason from simplistic lock and key or induced fit models to the more complex energetics model of transition state theory. Learning to understand these many facets of enzyme-substrate interactions and reasoning from multiple models present challenges where students incorrectly make connections between concepts or make no connection at all. This study investigated biochemistry students' understanding of enzyme-substrate interactions through the use of clinical interviews and a national administration (N = 707) of the Enzyme-Substrate Interactions Concept Inventory. Findings include misconceptions regarding the nature of enzyme-substrate interactions, naïve ideas about the active site, a lack of energetically driven interactions, and an incomplete understanding of the specificity pocket. © 2015 by the International Union of Biochemistry and Molecular Biology.

Supramolecular Assembly of Uridine Monophosphate (UMP) and Thymidine Monophosphate (TMP) with a Dinuclear Copper(II) Receptor.

PubMed

Rhaman, Md Mhahabubur; Powell, Douglas R; Hossain, Md Alamgir

2017-11-30

Understanding the intermolecular interactions between nucleotides and artificial receptors is crucial to understanding the role of nucleic acids in living systems. However, direct structural evidence showing precise interactions and bonding features of a nucleoside monophosphate (NMP) with a macrocycle-based synthetic molecule has not been provided so far. Herein, we present two novel crystal structures of uridine monophosphate (UMP) and thymidine monophosphate (TMP) complexes with a macrocycle-based dinuclear receptor. Structural characterization of these complexes reveals that the receptor recognizes UMP through coordinate-covalent interactions with phosphates and π-π stackings with nucleobases and TMP through coordinate-covalent interactions with phosphate groups. Furthermore, the receptor has been shown to effectively bind nucleoside monophosphates in the order of GMP > AMP > UMP > TMP > CMP in water at physiological pH, as investigated by an indicator displacement assay.

Groundwater dynamics in subterranean estuaries of coastal unconfined aquifers: Controls on submarine groundwater discharge and chemical inputs to the ocean

NASA Astrophysics Data System (ADS)

Robinson, Clare E.; Xin, Pei; Santos, Isaac R.; Charette, Matthew A.; Li, Ling; Barry, D. A.

2018-05-01

Sustainable coastal resource management requires sound understanding of interactions between coastal unconfined aquifers and the ocean as these interactions influence the flux of chemicals to the coastal ocean and the availability of fresh groundwater resources. The importance of submarine groundwater discharge in delivering chemical fluxes to the coastal ocean and the critical role of the subterranean estuary (STE) in regulating these fluxes is well recognized. STEs are complex and dynamic systems exposed to various physical, hydrological, geological, and chemical conditions that act on disparate spatial and temporal scales. This paper provides a review of the effect of factors that influence flow and salt transport in STEs, evaluates current understanding on the interactions between these influences, and synthesizes understanding of drivers of nutrient, carbon, greenhouse gas, metal and organic contaminant fluxes to the ocean. Based on this review, key research needs are identified. While the effects of density and tides are well understood, episodic and longer-period forces as well as the interactions between multiple influences remain poorly understood. Many studies continue to focus on idealized nearshore aquifer systems and future work needs to consider real world complexities such as geological heterogeneities, and non-uniform and evolving alongshore and cross-shore morphology. There is also a significant need for multidisciplinary research to unravel the interactions between physical and biogeochemical processes in STEs, as most existing studies treat these processes in isolation. Better understanding of this complex and dynamic system can improve sustainable management of coastal water resources under the influence of anthropogenic pressures and climate change.

Probing the interaction of bisintercalating (2,2':6',2″-terpyridine)platinum(II) complexes with glutathione and rabbit plasma.

PubMed

Harper, Benjamin W J; Morris, Thomas T; Gailer, Jürgen; Aldrich-Wright, Janice R

2016-10-01

Platinum(II) complexes have demonstrated considerable success in the treatment of cancer, but severe toxic side effects drive the search for new complexes with increased tumour selectivity and better efficacy. A critical concept that has to be considered in the context of designing novel Pt complexes is their interactions with biomolecules other than DNA. To this end, here the interactions of 16 previously reported bisintercalating (2,2':6',2″-terpyridine)platinum(II) complexes, [{Pt(terpy)} 2 μ-(X)] n+ (where X is a linker) with glutathione (GSH) by means of 1 H and 195 Pt NMR spectroscopy were investigated. The GSH half-life (GSH t 1/2 ) was determined following the incubation of each [{Pt(terpy)} 2 μ-(X)] n+ complex with GSH (8mM). It was observed that complexes 1-7, 11, 12 and 14-16 reacted more rapidly than cisplatin, whereas complexes 8-10, 13 and 17 reacted more slowly (≥200min). There was no apparent correlation between linker length and the GSH t 1/2 . In order to understand these interactions, two complexes: 1 (t 1/2 <1min) and a previously studied 17 [Pt(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)] (56MESS) (GSH t 1/2 =4080min) were incubated with rabbit plasma. A "metallomics" approach was used to analyse plasma for all platinum species at the 5 and the 60min time point and provided results that were congruent with the reaction of the selected Pt complexes with GSH. Our studies demonstrate that the combined application of NMR spectroscopy, cytotoxicity studies and a metallomics approach can contribute to better understand the interaction of [{Pt(terpy)} 2 μ-(X)] n+ complexes with biomolecules to better assess which compounds may be advanced to in vivo studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis of Context Dependence in Social Interaction Networks of a Massively Multiplayer Online Role-Playing Game

PubMed Central

Son, Seokshin; Kang, Ah Reum; Kim, Hyun-chul; Kwon, Taekyoung; Park, Juyong; Kim, Huy Kang

2012-01-01

Rapid advances in modern computing and information technology have enabled millions of people to interact online via various social network and gaming services. The widespread adoption of such online services have made possible analysis of large-scale archival data containing detailed human interactions, presenting a very promising opportunity to understand the rich and complex human behavior. In collaboration with a leading global provider of Massively Multiplayer Online Role-Playing Games (MMORPGs), here we present a network science-based analysis of the interplay between distinct types of user interaction networks in the virtual world. We find that their properties depend critically on the nature of the context-interdependence of the interactions, highlighting the complex and multilayered nature of human interactions, a robust understanding of which we believe may prove instrumental in the designing of more realistic future virtual arenas as well as provide novel insights to the science of collective human behavior. PMID:22496771

An integrative model of evolutionary covariance: a symposium on body shape in fishes.

PubMed

Walker, Jeffrey A

2010-12-01

A major direction of current and future biological research is to understand how multiple, interacting functional systems coordinate in producing a body that works. This understanding is complicated by the fact that organisms need to work well in multiple environments, with both predictable and unpredictable environmental perturbations. Furthermore, organismal design reflects a history of past environments and not a plan for future environments. How complex, interacting functional systems evolve, then, is a truly grand challenge. In accepting the challenge, an integrative model of evolutionary covariance is developed. The model combines quantitative genetics, functional morphology/physiology, and functional ecology. The model is used to convene scientists ranging from geneticists, to physiologists, to ecologists, to engineers to facilitate the emergence of body shape in fishes as a model system for understanding how complex, interacting functional systems develop and evolve. Body shape of fish is a complex morphology that (1) results from many developmental paths and (2) functions in many different behaviors. Understanding the coordination and evolution of the many paths from genes to body shape, body shape to function, and function to a working fish body in a dynamic environment is now possible given new technologies from genetics to engineering and new theoretical models that integrate the different levels of biological organization (from genes to ecology).

Computational structure analysis of biomacromolecule complexes by interface geometry.

PubMed

Mahdavi, Sedigheh; Salehzadeh-Yazdi, Ali; Mohades, Ali; Masoudi-Nejad, Ali

2013-12-01

The ability to analyze and compare protein-nucleic acid and protein-protein interaction interface has critical importance in understanding the biological function and essential processes occurring in the cells. Since high-resolution three-dimensional (3D) structures of biomacromolecule complexes are available, computational characterizing of the interface geometry become an important research topic in the field of molecular biology. In this study, the interfaces of a set of 180 protein-nucleic acid and protein-protein complexes are computed to understand the principles of their interactions. The weighted Voronoi diagram of the atoms and the Alpha complex has provided an accurate description of the interface atoms. Our method is implemented in the presence and absence of water molecules. A comparison among the three types of interaction interfaces show that RNA-protein complexes have the largest size of an interface. The results show a high correlation coefficient between our method and the PISA server in the presence and absence of water molecules in the Voronoi model and the traditional model based on solvent accessibility and the high validation parameters in comparison to the classical model. Copyright © 2013 Elsevier Ltd. All rights reserved.

Understanding Teachers' Routines to Inform Classroom Technology Design

ERIC Educational Resources Information Center

An, Pengcheng; Bakker, Saskia; Eggen, Berry

2017-01-01

Secondary school teachers have quite busy and complex routines in their classrooms. However, present classroom technologies usually require focused attention from teachers while being interacted with, which restricts their use in teachers' daily routines. Peripheral interaction is a human-computer interaction style that aims to enable interaction…

Chemical activation of molecules by metals: Experimental studies of electron distributions and bonding

NASA Astrophysics Data System (ADS)

Lichtenberg, Dennis L.

During this period some important breakthroughs were accomplished in understanding the relationships between molecular ionization energies and bond energies in transition metal complexes, in understanding the electronic factors of carbon-hydrogen bond activation by transition metals, in characterizing small molecule bonding interactions with transition metals, and in investigating intermolecular interactions in thin films of transition metal complexes. The formal relationship between measured molecular ionization energies and thermodynamic bond dissociation energies was developed into a single equation which unifies the treatment of covalent bonds, ionic bonds, and partially ionic bonds. The relationship was used to clarify the fundamental thermodynamic information relating to metal-hydrogen, metal-alkyl, and metal-metal bond energies. The ionization energies were also used to correlate the rates of carbonyl substitution reactions of (eta(sup 5)-C5H4X)Rh(CO)2 complexes, and to reveal the factors that control the stability of the transition state. The investigations of the fundamental interactions of C-H sigma and sigma* orbitals metals were continued with study of eta(sup 3)-1-methylallyl metal complexes. Direct observation and measurement of the stabilization energy provided by the agostic interaction of the C-H bond with the metal was obtained. The ability to observe the electronic effects of intermolecular interactions by comparing the ionizations of metal complexes in the gas phase with the ionizations of thin solid organometallic films prepared in ultra-high vacuum was established. Most significantly, the scanning tunneling microscope imaging of these thin films was accomplished.

Crystal structure of the C-terminal SH3 domain of the adaptor protein GADS in complex with SLP-76 motif peptide reveals a unique SH3-SH3 interaction.

PubMed

Dimasi, Nazzareno

2007-01-01

The Grb2-like adaptor protein GADS is essential for tyrosine kinase-dependent signaling in T lymphocytes. Following T cell receptor ligation, GADS interacts through its C-terminal SH3 domain with the adaptors SLP-76 and LAT, to form a multiprotein signaling complex that is crucial for T cell activation. To understand the structural basis for the selective recognition of GADS by SLP-76, herein is reported the crystal structure at 1.54 Angstrom of the C-terminal SH3 domain of GADS bound to the SLP-76 motif 233-PSIDRSTKP-241, which represents the minimal binding site. In addition to the unique structural features adopted by the bound SLP-76 peptide, the complex structure reveals a unique SH3-SH3 interaction. This homophilic interaction, which is observed in presence of the SLP-76 peptide and is present in solution, extends our understanding of the molecular mechanisms that could be employed by modular proteins to increase their signaling transduction specificity.

A Printing-Centric Approach to the Electrostatic Modification of Polymer/Clay Composites for use in 3D Direct-Ink Writing

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

Rauzan, Brittany; Lehman, Sean; McCracken, Josell

Polymer/clay composite inks are exceptionally useful materials for fabrication processes based on 3D direct-ink writing, however, there remains an insufficient understanding of how their physiochemical dynamics impact printability. Using a model system, N-isopropylacrylamide/Laponite, the electrostatic interactions between Laponite platelets are modified to tune critical rheological properties in order to improve printability. Rheological measurements and X-ray scattering experiments are carried out to monitor the nano/micro-structural dynamics and complex physicochemical interactions of Laponite as it impacts complex modulus in the linear region, flow behavior, thixotropy, and yield stress of the composite ink. Modification of the electrostatic interactions between platelets reduces the yieldmore » stress of the material, while maintaining a complex microstructure that allows for sufficient recovery times upon removal of stress to form stable, and thus printable, filaments. A printing-centric approach is established based on a fundamental understanding of electrostatic inter-particle interactions, harnessing the innate microstructure of Laponite in 3D direct-ink writing of composites.« less

Modeling Complex Cross-Systems Software Interfaces Using SysML

NASA Technical Reports Server (NTRS)

Mandutianu, Sanda; Morillo, Ron; Simpson, Kim; Liepack, Otfrid; Bonanne, Kevin

2013-01-01

The complex flight and ground systems for NASA human space exploration are designed, built, operated and managed as separate programs and projects. However, each system relies on one or more of the other systems in order to accomplish specific mission objectives, creating a complex, tightly coupled architecture. Thus, there is a fundamental need to understand how each system interacts with the other. To determine if a model-based system engineering approach could be utilized to assist with understanding the complex system interactions, the NASA Engineering and Safety Center (NESC) sponsored a task to develop an approach for performing cross-system behavior modeling. This paper presents the results of applying Model Based Systems Engineering (MBSE) principles using the System Modeling Language (SysML) to define cross-system behaviors and how they map to crosssystem software interfaces documented in system-level Interface Control Documents (ICDs).

Analysis of complex neural circuits with nonlinear multidimensional hidden state models

PubMed Central

Friedman, Alexander; Slocum, Joshua F.; Tyulmankov, Danil; Gibb, Leif G.; Altshuler, Alex; Ruangwises, Suthee; Shi, Qinru; Toro Arana, Sebastian E.; Beck, Dirk W.; Sholes, Jacquelyn E. C.; Graybiel, Ann M.

2016-01-01

A universal need in understanding complex networks is the identification of individual information channels and their mutual interactions under different conditions. In neuroscience, our premier example, networks made up of billions of nodes dynamically interact to bring about thought and action. Granger causality is a powerful tool for identifying linear interactions, but handling nonlinear interactions remains an unmet challenge. We present a nonlinear multidimensional hidden state (NMHS) approach that achieves interaction strength analysis and decoding of networks with nonlinear interactions by including latent state variables for each node in the network. We compare NMHS to Granger causality in analyzing neural circuit recordings and simulations, improvised music, and sociodemographic data. We conclude that NMHS significantly extends the scope of analyses of multidimensional, nonlinear networks, notably in coping with the complexity of the brain. PMID:27222584

Decoding molecular interactions in microbial communities

PubMed Central

Abreu, Nicole A.; Taga, Michiko E.

2016-01-01

Microbial communities govern numerous fundamental processes on earth. Discovering and tracking molecular interactions among microbes is critical for understanding how single species and complex communities impact their associated host or natural environment. While recent technological developments in DNA sequencing and functional imaging have led to new and deeper levels of understanding, we are limited now by our inability to predict and interpret the intricate relationships and interspecies dependencies within these communities. In this review, we highlight the multifaceted approaches investigators have taken within their areas of research to decode interspecies molecular interactions that occur between microbes. Understanding these principles can give us greater insight into ecological interactions in natural environments and within synthetic consortia. PMID:27417261

Demystifying the cytokine network: Mathematical models point the way.

PubMed

Morel, Penelope A; Lee, Robin E C; Faeder, James R

2017-10-01

Cytokines provide the means by which immune cells communicate with each other and with parenchymal cells. There are over one hundred cytokines and many exist in families that share receptor components and signal transduction pathways, creating complex networks. Reductionist approaches to understanding the role of specific cytokines, through the use of gene-targeted mice, have revealed further complexity in the form of redundancy and pleiotropy in cytokine function. Creating an understanding of the complex interactions between cytokines and their target cells is challenging experimentally. Mathematical and computational modeling provides a robust set of tools by which complex interactions between cytokines can be studied and analyzed, in the process creating novel insights that can be further tested experimentally. This review will discuss and provide examples of the different modeling approaches that have been used to increase our understanding of cytokine networks. This includes discussion of knowledge-based and data-driven modeling approaches and the recent advance in single-cell analysis. The use of modeling to optimize cytokine-based therapies will also be discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Complexity of Language Learning

ERIC Educational Resources Information Center

Nelson, Charles

2011-01-01

This paper takes a complexity theory approach to looking at language learning, an approach that investigates how language learners adapt to and interact with people and their environment. Based on interviews with four graduate students, it shows how complexity theory can help us understand both the situatedness of language learning and also…

Supramolecular Assembly of Uridine Monophosphate (UMP) and Thymidine Monophosphate (TMP) with a Dinuclear Copper(II) Receptor

PubMed Central

2017-01-01

Understanding the intermolecular interactions between nucleotides and artificial receptors is crucial to understanding the role of nucleic acids in living systems. However, direct structural evidence showing precise interactions and bonding features of a nucleoside monophosphate (NMP) with a macrocycle-based synthetic molecule has not been provided so far. Herein, we present two novel crystal structures of uridine monophosphate (UMP) and thymidine monophosphate (TMP) complexes with a macrocycle-based dinuclear receptor. Structural characterization of these complexes reveals that the receptor recognizes UMP through coordinate–covalent interactions with phosphates and π–π stackings with nucleobases and TMP through coordinate–covalent interactions with phosphate groups. Furthermore, the receptor has been shown to effectively bind nucleoside monophosphates in the order of GMP > AMP > UMP > TMP > CMP in water at physiological pH, as investigated by an indicator displacement assay. PMID:29214233

Getting a Grip on Complexes

PubMed Central

Nie, Yan; Viola, Cristina; Bieniossek, Christoph; Trowitzsch, Simon; Vijay-achandran, Lakshmi Sumitra; Chaillet, Maxime; Garzoni, Frederic; Berger, Imre

2009-01-01

We are witnessing tremendous advances in our understanding of the organization of life. Complete genomes are being deciphered with ever increasing speed and accuracy, thereby setting the stage for addressing the entire gene product repertoire of cells, towards understanding whole biological systems. Advances in bioinformatics and mass spectrometric techniques have revealed the multitude of interactions present in the proteome. Multiprotein complexes are emerging as a paramount cornerstone of biological activity, as many proteins appear to participate, stably or transiently, in large multisubunit assemblies. Analysis of the architecture of these assemblies and their manifold interactions is imperative for understanding their function at the molecular level. Structural genomics efforts have fostered the development of many technologies towards achieving the throughput required for studying system-wide single proteins and small interaction motifs at high resolution. The present shift in focus towards large multiprotein complexes, in particular in eukaryotes, now calls for a likewise concerted effort to develop and provide new technologies that are urgently required to produce in quality and quantity the plethora of multiprotein assemblies that form the complexome, and to routinely study their structure and function at the molecular level. Current efforts towards this objective are summarized and reviewed in this contribution. PMID:20514218

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

PubMed

Goody, Michelle F; Henry, Clarissa A

2010-06-01

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

Environmental stress and whole-tree physiology

Treesearch

Peter L. Jr. Lorio

1993-01-01

Interactions among bark beetles, pathogens, and conifers constitute a triangle. Another triangle of interactions exist among the invading organism (bark beetles and pathogens), the trees, and the environment. How important, variable or constant, simple or complex, is the role of trees in these triangles? Understanding the wide range of interactions that take place...

Interaction Network Estimation: Predicting Problem-Solving Diversity in Interactive Environments

ERIC Educational Resources Information Center

Eagle, Michael; Hicks, Drew; Barnes, Tiffany

2015-01-01

Intelligent tutoring systems and computer aided learning environments aimed at developing problem solving produce large amounts of transactional data which make it a challenge for both researchers and educators to understand how students work within the environment. Researchers have modeled student-tutor interactions using complex networks in…

Estimating the Local Size and Coverage of Interaction Network Regions

ERIC Educational Resources Information Center

Eagle, Michael; Barnes, Tiffany

2015-01-01

Interactive problem solving environments, such as intelligent tutoring systems and educational video games, produce large amounts of transactional data which make it a challenge for both researchers and educators to understand how students work within the environment. Researchers have modeled the student-tutor interactions using complex network…

Facilitating Trust Engenderment in Secondary School Nurse Interactions with Students

ERIC Educational Resources Information Center

Summach, Anne H. J.

2011-01-01

School nurses are involved in a complex framework of interactions with students, other professionals, parents, and administrators. Trust between nurse and student is critical for interaction effectiveness. The goal of this study was to understand through phenomenology the process of engendering trust in school nurse-high school student…

Improving protein complex classification accuracy using amino acid composition profile.

PubMed

Huang, Chien-Hung; Chou, Szu-Yu; Ng, Ka-Lok

2013-09-01

Protein complex prediction approaches are based on the assumptions that complexes have dense protein-protein interactions and high functional similarity between their subunits. We investigated those assumptions by studying the subunits' interaction topology, sequence similarity and molecular function for human and yeast protein complexes. Inclusion of amino acids' physicochemical properties can provide better understanding of protein complex properties. Principal component analysis is carried out to determine the major features. Adopting amino acid composition profile information with the SVM classifier serves as an effective post-processing step for complexes classification. Improvement is based on primary sequence information only, which is easy to obtain. Copyright © 2013 Elsevier Ltd. All rights reserved.

A framework for complexity in palliative care: A qualitative study with patients, family carers and professionals.

PubMed

Pask, Sophie; Pinto, Cathryn; Bristowe, Katherine; van Vliet, Liesbeth; Nicholson, Caroline; Evans, Catherine J; George, Rob; Bailey, Katharine; Davies, Joanna M; Guo, Ping; Daveson, Barbara A; Higginson, Irene J; Murtagh, Fliss Em

2018-06-01

Palliative care patients are often described as complex but evidence on complexity is limited. We need to understand complexity, including at individual patient-level, to define specialist palliative care, characterise palliative care populations and meaningfully compare interventions/outcomes. To explore palliative care stakeholders' views on what makes a patient more or less complex and insights on capturing complexity at patient-level. In-depth qualitative interviews, analysed using Framework analysis. Semi-structured interviews across six UK centres with patients, family, professionals, managers and senior leads, purposively sampled by experience, background, location and setting (hospital, hospice and community). 65 participants provided an understanding of complexity, which extended far beyond the commonly used physical, psychological, social and spiritual domains. Complexity included how patients interact with family/professionals, how services' respond to needs and societal perspectives on care. 'Pre-existing', 'cumulative' and 'invisible' complexity are further important dimensions to delivering effective palliative and end-of-life care. The dynamic nature of illness and needs over time was also profoundly influential. Adapting Bronfenbrenner's Ecological Systems Theory, we categorised findings into the microsystem (person, needs and characteristics), chronosystem (dynamic influences of time), mesosystem (interactions with family/health professionals), exosystem (palliative care services/systems) and macrosystem (societal influences). Stakeholders found it acceptable to capture complexity at the patient-level, with perceived benefits for improving palliative care resource allocation. Our conceptual framework encompasses additional elements beyond physical, psychological, social and spiritual domains and advances systematic understanding of complexity within the context of palliative care. This framework helps capture patient-level complexity and target resource provision in specialist palliative care.

The sleeping brain as a complex system.

PubMed

Olbrich, Eckehard; Achermann, Peter; Wennekers, Thomas

2011-10-13

'Complexity science' is a rapidly developing research direction with applications in a multitude of fields that study complex systems consisting of a number of nonlinear elements with interesting dynamics and mutual interactions. This Theme Issue 'The complexity of sleep' aims at fostering the application of complexity science to sleep research, because the brain in its different sleep stages adopts different global states that express distinct activity patterns in large and complex networks of neural circuits. This introduction discusses the contributions collected in the present Theme Issue. We highlight the potential and challenges of a complex systems approach to develop an understanding of the brain in general and the sleeping brain in particular. Basically, we focus on two topics: the complex networks approach to understand the changes in the functional connectivity of the brain during sleep, and the complex dynamics of sleep, including sleep regulation. We hope that this Theme Issue will stimulate and intensify the interdisciplinary communication to advance our understanding of the complex dynamics of the brain that underlies sleep and consciousness.

Progress in the Analysis of Complex Atmospheric Particles

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

Laskin, Alexander; Gilles, Mary K.; Knopf, Daniel A.

2016-06-16

This manuscript presents an overview on recent advances in field and laboratory studies of atmospheric particles formed in processes of environmental air-surfaces interactions. The overarching goal of these studies is to advance predictive understanding of atmospheric particle composition, particle chemistry during aging, and their environmental impacts. The diversity between chemical constituents and lateral heterogeneity within individual particles adds to the chemical complexity of particles and their surfaces. Once emitted, particles undergo transformation via atmospheric aging processes that further modify their complex composition. We highlight a range of modern analytical approaches that enable multi-modal chemical characterization of particles with both molecularmore » and lateral specificity. When combined, they provide a comprehensive arsenal of tools for understanding the nature of particles at air-surface interactions and their reactivity and transformations with atmospheric aging. We discuss applications of these novel approaches in recent studies and highlight additional research areas to explore environmental effects of air-surface interactions.« less

Progress in the analysis of complex atmospheric particles

DOE PAGES

Laskin, Alexander; Gilles, Mary K.; Knopf, Daniel A.; ...

2016-06-01

This study presents an overview of recent advances in field and laboratory studies of atmospheric particles formed in processes of environmental air-surface interactions. The overarching goal of these studies is to advance predictive understanding of atmospheric particle composition, particle chemistry during aging, and their environmental impacts. The diversity between chemical constituents and lateral heterogeneity within individual particles adds to the chemical complexity of particles and their surfaces. Once emitted, particles undergo transformation via atmospheric aging processes that further modify their complex composition. We highlight a range of modern analytical approaches that enable multimodal chemical characterization of particles with both molecularmore » and lateral specificity. When combined, these approaches provide a comprehensive arsenal of tools for understanding the nature of particles at air-surface interactions and their reactivity and transformations with atmospheric aging. We discuss applications of these novel approaches in recent studies and highlight additional research areas to explore the environmental effects of air-surface interactions.« less

Snap Shots: Using Photography for Intercultural Awareness and Understanding

ERIC Educational Resources Information Center

Alvaray, Luisela

2014-01-01

Watching images through mass media presents a challenge for understanding the complexities of different cultures within and outside the United States. Photographic images, in particular, are ubiquitous in our mediated world, populating old and interactive media and many times serving to perpetuate established codes of understanding and action.…

Insight to the Interaction of the Dihydrolipoamide Acetyltransferase (E2) Core with the Peripheral Components in the Escherichia coli Pyruvate Dehydrogenase Complex via Multifaceted Structural Approaches*

PubMed Central

Chandrasekhar, Krishnamoorthy; Wang, Junjie; Arjunan, Palaniappa; Sax, Martin; Park, Yun-Hee; Nemeria, Natalia S.; Kumaran, Sowmini; Song, Jaeyoung; Jordan, Frank; Furey, William

2013-01-01

Multifaceted structural approaches were undertaken to investigate interaction of the E2 component with E3 and E1 components from the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc), as a representative of the PDHc from Gram-negative bacteria. The crystal structure of E3 at 2.5 Å resolution reveals similarity to other E3 structures and was an important starting point for understanding interaction surfaces between E3 and E2. Biochemical studies revealed that R129E-E2 and R150E-E2 substitutions in the peripheral subunit-binding domain (PSBD) of E2 greatly diminished PDHc activity, affected interactions with E3 and E1 components, and affected reductive acetylation of E2. Because crystal structures are unavailable for any complete E2-containing complexes, peptide-specific hydrogen/deuterium exchange mass spectrometry was used to identify loci of interactions between 3-lipoyl E2 and E3. Two peptides from the PSBD, including Arg-129, and three peptides from E3 displayed statistically significant reductions in deuterium uptake resulting from interaction between E3 and E2. Of the peptides identified on E3, two were from the catalytic site, and the third was from the interface domain, which for all known E3 structures is believed to interact with the PSBD. NMR clearly demonstrates that there is no change in the lipoyl domain structure on complexation with E3. This is the first instance where the entire wild-type E2 component was employed to understand interactions with E3. A model for PSBD-E3 binding was independently constructed and found to be consistent with the importance of Arg-129, as well as revealing other electrostatic interactions likely stabilizing this complex. PMID:23580650

Insight to the interaction of the dihydrolipoamide acetyltransferase (E2) core with the peripheral components in the Escherichia coli pyruvate dehydrogenase complex via multifaceted structural approaches.

PubMed

Chandrasekhar, Krishnamoorthy; Wang, Junjie; Arjunan, Palaniappa; Sax, Martin; Park, Yun-Hee; Nemeria, Natalia S; Kumaran, Sowmini; Song, Jaeyoung; Jordan, Frank; Furey, William

2013-05-24

Multifaceted structural approaches were undertaken to investigate interaction of the E2 component with E3 and E1 components from the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc), as a representative of the PDHc from Gram-negative bacteria. The crystal structure of E3 at 2.5 Å resolution reveals similarity to other E3 structures and was an important starting point for understanding interaction surfaces between E3 and E2. Biochemical studies revealed that R129E-E2 and R150E-E2 substitutions in the peripheral subunit-binding domain (PSBD) of E2 greatly diminished PDHc activity, affected interactions with E3 and E1 components, and affected reductive acetylation of E2. Because crystal structures are unavailable for any complete E2-containing complexes, peptide-specific hydrogen/deuterium exchange mass spectrometry was used to identify loci of interactions between 3-lipoyl E2 and E3. Two peptides from the PSBD, including Arg-129, and three peptides from E3 displayed statistically significant reductions in deuterium uptake resulting from interaction between E3 and E2. Of the peptides identified on E3, two were from the catalytic site, and the third was from the interface domain, which for all known E3 structures is believed to interact with the PSBD. NMR clearly demonstrates that there is no change in the lipoyl domain structure on complexation with E3. This is the first instance where the entire wild-type E2 component was employed to understand interactions with E3. A model for PSBD-E3 binding was independently constructed and found to be consistent with the importance of Arg-129, as well as revealing other electrostatic interactions likely stabilizing this complex.

Applications of nuclear magnetic resonance spectroscopy for the understanding of enantiomer separation mechanisms in capillary electrophoresis.

PubMed

Salgado, Antonio; Chankvetadze, Bezhan

2016-10-07

This review deals with the applications of nuclear magnetic resonance (NMR) spectroscopy to understand the mechanisms of chiral separation in capillary electrophoresis (CE). It is accepted that changes observed in the separation process, including the reversal of enantiomer migration order (EMO), can be caused by subtle modifications in the molecular recognition mechanisms between enantiomer and chiral selector. These modifications may imply minor structural differences in those selector-selectand complexes that arise from the above mentioned interactions. Therefore, it is mandatory to understand the fine intermolecular interactions between analytes and chiral selectors. In other words, it is necessary to know in detail the structures of the complexes formed by the enantiomer (selectand) and the selector. Any differences in the structures of these complexes arising from either enantiomer should be detected, so that enantiomeric bias in the separation process could be explained. As to the nature of these interactions, those have been extensively reviewed, and it is not intended to be discussed here. These interactions contemplate ionic, ion-dipole and dipole-dipole interactions, hydrogen bonding, van der Waals forces, π-π stacking, steric and hydrophobic interactions. The main subject of this review is to describe how NMR spectroscopy helps to gain insight into the non-covalent intermolecular interactions between selector and selectand that lead to enantiomer separation by CE. Examples in which diastereomeric species are created by covalent (irreversible) derivatization will not be considered here. This review is structured upon the different structural classes of chiral selectors employed in CE, in which NMR spectroscopy has made substantial contributions to rationalize the observed enantioseparations. Cases in which other techniques complement NMR spectroscopic data are also mentioned. Copyright © 2016 Elsevier B.V. All rights reserved.

Towards a holistic understanding of the beneficial interactions across the Populus microbiome

DOE PAGES

Hacquard, Stéphane; Schadt, Christopher W.

2014-11-24

Interactions between trees and microorganisms are extremely complex and the multispecies networks resulting from these associations have consequences for plant growth and productivity. However, a more holistic view is needed to better understand trees as ecosystems and superorganisms, where many interacting species contribute to the overall stability of the system. While much progress has been made on microbial communities associated with individual tree niches and the molecular interactions between model symbiotic partners, there is still a lack of knowledge of the multi-component interactions necessary for holistic ecosystem-level understanding. Finally, we review recent studies in Populus to emphasize the importance ofmore » such holistic efforts across the leaf, stem and rooting zones, and discuss prospects for future research in these important ecosystems.« less

Flow interactions with cells and tissues: cardiovascular flows and fluid-structure interactions. Sixth International Bio-Fluid Mechanics Symposium and Workshop, March 28-30, 2008, Pasadena, California.

PubMed

Friedman, Morton H; Krams, Rob; Chandran, Krishnan B

2010-03-01

Interactions between flow and biological cells and tissues are intrinsic to the circulatory, respiratory, digestive and genitourinary systems. In the circulatory system, an understanding of the complex interaction between the arterial wall (a living multi-component organ with anisotropic, nonlinear material properties) and blood (a shear-thinning fluid with 45% by volume consisting of red blood cells, platelets, and white blood cells) is vital to our understanding of the physiology of the human circulation and the etiology and development of arterial diseases, and to the design and development of prosthetic implants and tissue-engineered substitutes. Similarly, an understanding of the complex dynamics of flow past native human heart valves and the effect of that flow on the valvular tissue is necessary to elucidate the etiology of valvular diseases and in the design and development of valve replacements. In this paper we address the influence of biomechanical factors on the arterial circulation. The first part presents our current understanding of the impact of blood flow on the arterial wall at the cellular level and the relationship between flow-induced stresses and the etiology of atherosclerosis. The second part describes recent advances in the application of fluid-structure interaction analysis to arterial flows and the dynamics of heart valves.

Structure, dynamics and biophysics of the cytoplasmic protein–protein complexes of the bacterial phosphoenolpyruvate: Sugar phosphotransferase system

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

Clore, G. Marius; Venditti, Vincenzo

2013-10-01

The bacterial phosphotransferase system (PTS) couples phosphoryl transfer, via a series of bimolecular protein–protein interactions, to sugar transport across the membrane. The multitude of complexes in the PTS provides a paradigm for studying protein interactions, and for understanding how the same binding surface can specifically recognize a diverse array of targets. Fifteen years of work aimed at solving the solution structures of all soluble protein–protein complexes of the PTS has served as a test bed for developing NMR and integrated hybrid approaches to study larger complexes in solution and to probe transient, spectroscopically invisible states, including encounter complexes. We reviewmore » these approaches, highlighting the problems that can be tackled with these methods, and summarize the current findings on protein interactions.« less

Quantitative genetic-interaction mapping in mammalian cells

PubMed Central

Roguev, Assen; Talbot, Dale; Negri, Gian Luca; Shales, Michael; Cagney, Gerard; Bandyopadhyay, Sourav; Panning, Barbara; Krogan, Nevan J

2013-01-01

Mapping genetic interactions (GIs) by simultaneously perturbing pairs of genes is a powerful tool for understanding complex biological phenomena. Here we describe an experimental platform for generating quantitative GI maps in mammalian cells using a combinatorial RNA interference strategy. We performed ~11,000 pairwise knockdowns in mouse fibroblasts, focusing on 130 factors involved in chromatin regulation to create a GI map. Comparison of the GI and protein-protein interaction (PPI) data revealed that pairs of genes exhibiting positive GIs and/or similar genetic profiles were predictive of the corresponding proteins being physically associated. The mammalian GI map identified pathways and complexes but also resolved functionally distinct submodules within larger protein complexes. By integrating GI and PPI data, we created a functional map of chromatin complexes in mouse fibroblasts, revealing that the PAF complex is a central player in the mammalian chromatin landscape. PMID:23407553

ViSEN: methodology and software for visualization of statistical epistasis networks

PubMed Central

Hu, Ting; Chen, Yuanzhu; Kiralis, Jeff W.; Moore, Jason H.

2013-01-01

The non-linear interaction effect among multiple genetic factors, i.e. epistasis, has been recognized as a key component in understanding the underlying genetic basis of complex human diseases and phenotypic traits. Due to the statistical and computational complexity, most epistasis studies are limited to interactions with an order of two. We developed ViSEN to analyze and visualize epistatic interactions of both two-way and three-way. ViSEN not only identifies strong interactions among pairs or trios of genetic attributes, but also provides a global interaction map that shows neighborhood and clustering structures. This visualized information could be very helpful to infer the underlying genetic architecture of complex diseases and to generate plausible hypotheses for further biological validations. ViSEN is implemented in Java and freely available at https://sourceforge.net/projects/visen/. PMID:23468157

ShapeShop: Towards Understanding Deep Learning Representations via Interactive Experimentation.

PubMed

Hohman, Fred; Hodas, Nathan; Chau, Duen Horng

2017-05-01

Deep learning is the driving force behind many recent technologies; however, deep neural networks are often viewed as "black-boxes" due to their internal complexity that is hard to understand. Little research focuses on helping people explore and understand the relationship between a user's data and the learned representations in deep learning models. We present our ongoing work, ShapeShop, an interactive system for visualizing and understanding what semantics a neural network model has learned. Built using standard web technologies, ShapeShop allows users to experiment with and compare deep learning models to help explore the robustness of image classifiers.

An ecohydrologic model for a shallow groundwater urban environment.

PubMed

Arden, Sam; Ma, Xin Cissy; Brown, Mark

2014-01-01

The urban environment is a patchwork of natural and artificial surfaces that results in complex interactions with and impacts to natural hydrologic cycles. Evapotranspiration is a major hydrologic flow that is often altered through urbanization, although the mechanisms of change are sometimes difficult to tease out due to difficulty in effectively simulating soil-plant-atmosphere interactions. This paper introduces a simplified yet realistic model that is a combination of existing surface runoff and ecohydrology models designed to increase the quantitative understanding of complex urban hydrologic processes. Results demonstrate that the model is capable of simulating the long-term variability of major hydrologic fluxes as a function of impervious surface, temperature, water table elevation, canopy interception, soil characteristics, precipitation and complex mechanisms of plant water uptake. These understandings have potential implications for holistic urban water system management.

FuturICT: Participatory computing to understand and manage our complex world in a more sustainable and resilient way

NASA Astrophysics Data System (ADS)

Helbing, D.; Bishop, S.; Conte, R.; Lukowicz, P.; McCarthy, J. B.

2012-11-01

We have built particle accelerators to understand the forces that make up our physical world. Yet, we do not understand the principles underlying our strongly connected, techno-socio-economic systems. We have enabled ubiquitous Internet connectivity and instant, global information access. Yet we do not understand how it impacts our behavior and the evolution of society. To fill the knowledge gaps and keep up with the fast pace at which our world is changing, a Knowledge Accelerator must urgently be created. The financial crisis, international wars, global terror, the spreading of diseases and cyber-crime as well as demographic, technological and environmental change demonstrate that humanity is facing serious challenges. These problems cannot be solved within the traditional paradigms. Moving our attention from a component-oriented view of the world to an interaction-oriented view will allow us to understand the complex systems we have created and the emergent collective phenomena characterising them. This paradigm shift will enable new solutions to long-standing problems, very much as the shift from a geocentric to a heliocentric worldview has facilitated modern physics and the ability to launch satellites. The FuturICT flagship project will develop new science and technology to manage our future in a complex, strongly connected world. For this, it will combine the power of information and communication technology (ICT) with knowledge from the social and complexity sciences. ICT will provide the data to boost the social sciences into a new era. Complexity science will shed new light on the emergent phenomena in socially interactive systems, and the social sciences will provide a better understanding of the opportunities and risks of strongly networked systems, in particular future ICT systems. Hence, the envisaged FuturICT flagship will create new methods and instruments to tackle the challenges of the 21st century. FuturICT could indeed become one of the most important scientific endeavours ever, by revealing the principles that make socially interactive systems work well, by inspiring the creation of new platforms to explore our possible futures, and by initiating an era of social and socio-inspired innovations.

Systems thinking perspectives applied to healthcare transition for youth with disabilities: a paradigm shift for practice, policy and research.

PubMed

Hamdani, Y; Jetha, A; Norman, C

2011-11-01

Healthcare transition (HCT) for youth with disabilities is a complex phenomenon influenced by multiple interacting factors, including health, personal and environmental factors. Current research on the transition to adulthood for disabled youth has primarily focused on identifying these multilevel factors to guide the development of interventions to improve the HCT process. However, little is known about how this complex array of factors interacts and contributes to successful HCT. Systems thinking provides a theoretically informed perspective that accounts for complexity and can contribute to enhanced understanding of the interactions among HCT factors. The objective of this paper is to introduce general concepts of systems thinking as applied to HCT practice and research. Several systems thinking concepts and principles are introduced and a discussion of HCT as a complex system is provided. Systems dynamics methodology is described as one systems method for conceptualizing HCT. A preliminary systems dynamics model is presented to facilitate discourse on the application of systems thinking principles to HCT practice, policy and research. An understanding of the complex interactions and patterns of relationships in HCT can assist health policy makers and practitioners in determining key areas of intervention, the impact of these interventions on the system and the potential intended and unintended consequences of change. This paper provides initial examination of applying systems thinking to inform future research and practice on HCT. © 2011 Blackwell Publishing Ltd.

Interactions Among Plants, Insects, and Microbes: Elucidation of Inter-Organismal Chemical Communications in Agricultural Ecology.

PubMed

Beck, John J; Alborn, Hans; Block, Anna; Christensen, Shawn A; Hunter, Charles T; Rering, Caitlin C; Seidl-Adams, Irmgard; Stuhl, Charles; Torto, Baldwyn; Tumlinson, James H

2018-06-12

The last two decades have witnessed a sustained increase in the study of plant-emitted volatiles and their role in plant-insect, plant-microbe and plant-plant interactions. While each of these binary systems involves complex chemical and biochemical processes between two organisms, the progression of increasing complexity of a ternary system (i.e., plant-insect-microbe), and the study of a ternary system requires non-trivial planning. This planning can include: an experimental design that factors in potential overarching ecological interactions regarding the binary or ternary system; correctly identifying and understanding unexpected observations that may occur during the experiment; and, thorough interpretation of the resultant data. This challenge of planning, performing and interpreting a plant's defensive response to multiple biotic stressors will be even greater when abiotic stressors (i.e., temperature or water) are factored into the system. To fully understand the system, we need to not only continue to investigate and understand the volatile profiles, but also include and understand the biochemistry of the plant's response to these stressors. In this paper, we provide examples and discuss interaction considerations with respect to how readers and future authors of the Journal of Agricultural and Food Chemistry can contribute their expertise toward the extraction and interpretation of chemical information exchanged between agricultural commodities and their associated pests. This holistic, multidisciplinary and thoughtful approach to interactions of plants, insects, and microbes, and the resultant response of the plants, can lead to a better understanding of agricultural ecology, in turn leading to practical and viable solutions to agricultural problems.

Interactive, process-oriented climate modeling with CLIMLAB

NASA Astrophysics Data System (ADS)

Rose, B. E. J.

2016-12-01

Global climate is a complex emergent property of the rich interactions between simpler components of the climate system. We build scientific understanding of this system by breaking it down into component process models (e.g. radiation, large-scale dynamics, boundary layer turbulence), understanding each components, and putting them back together. Hands-on experience and freedom to tinker with climate models (whether simple or complex) is invaluable for building physical understanding. CLIMLAB is an open-ended software engine for interactive, process-oriented climate modeling. With CLIMLAB you can interactively mix and match model components, or combine simpler process models together into a more comprehensive model. It was created primarily to support classroom activities, using hands-on modeling to teach fundamentals of climate science at both undergraduate and graduate levels. CLIMLAB is written in Python and ties in with the rich ecosystem of open-source scientific Python tools for numerics and graphics. The Jupyter Notebook format provides an elegant medium for distributing interactive example code. I will give an overview of the current capabilities of CLIMLAB, the curriculum we have developed thus far, and plans for the future. Using CLIMLAB requires some basic Python coding skills. We consider this an educational asset, as we are targeting upper-level undergraduates and Python is an increasingly important language in STEM fields.

Eukaryotic Replicative Helicase Subunit Interaction with DNA and Its Role in DNA Replication

PubMed Central

Martinez, Matthew P.; Wacker, Amanda L.; Bruck, Irina; Kaplan, Daniel L.

2017-01-01

The replicative helicase unwinds parental double-stranded DNA at a replication fork to provide single-stranded DNA templates for the replicative polymerases. In eukaryotes, the replicative helicase is composed of the Cdc45 protein, the heterohexameric ring-shaped Mcm2-7 complex, and the tetrameric GINS complex (CMG). The CMG proteins bind directly to DNA, as demonstrated by experiments with purified proteins. The mechanism and function of these DNA-protein interactions are presently being investigated, and a number of important discoveries relating to how the helicase proteins interact with DNA have been reported recently. While some of the protein-DNA interactions directly relate to the unwinding function of the enzyme complex, other protein-DNA interactions may be important for minichromosome maintenance (MCM) loading, origin melting or replication stress. This review describes our current understanding of how the eukaryotic replicative helicase subunits interact with DNA structures in vitro, and proposed models for the in vivo functions of replicative helicase-DNA interactions are also described. PMID:28383499

Review of Tropical-Extratropical Teleconnections on Intraseasonal Time Scales

NASA Astrophysics Data System (ADS)

Stan, Cristiana; Straus, David M.; Frederiksen, Jorgen S.; Lin, Hai; Maloney, Eric D.; Schumacher, Courtney

2017-12-01

The interactions and teleconnections between the tropical and midlatitude regions on intraseasonal time scales are an important modulator of tropical and extratropical circulation anomalies and their associated weather patterns. These interactions arise due to the impact of the tropics on the extratropics, the impact of the midlatitudes on the tropics, and two-way interactions between the regions. Observational evidence, as well as theoretical studies with models of complexity ranging from the linear barotropic framework to intricate Earth system models, suggest the involvement of a myriad of processes and mechanisms in generating and maintaining these interconnections. At this stage, our understanding of these teleconnections is primarily a collection of concepts; a comprehensive theoretical framework has yet to be established. These intraseasonal teleconnections are increasingly recognized as an untapped source of potential subseasonal predictability. However, the complexity and diversity of mechanisms associated with these teleconnections, along with the lack of a conceptual framework to relate them, prevent this potential predictability from being translated into realized forecast skill. This review synthesizes our progress in understanding the observed characteristics of intraseasonal tropical-extratropical interactions and their associated mechanisms, identifies the significant gaps in this understanding, and recommends new research endeavors to address the remaining challenges.

Ultrastable cellulosome-adhesion complex tightens under load.

PubMed

Schoeler, Constantin; Malinowska, Klara H; Bernardi, Rafael C; Milles, Lukas F; Jobst, Markus A; Durner, Ellis; Ott, Wolfgang; Fried, Daniel B; Bayer, Edward A; Schulten, Klaus; Gaub, Hermann E; Nash, Michael A

2014-12-08

Challenging environments have guided nature in the development of ultrastable protein complexes. Specialized bacteria produce discrete multi-component protein networks called cellulosomes to effectively digest lignocellulosic biomass. While network assembly is enabled by protein interactions with commonplace affinities, we show that certain cellulosomal ligand-receptor interactions exhibit extreme resistance to applied force. Here, we characterize the ligand-receptor complex responsible for substrate anchoring in the Ruminococcus flavefaciens cellulosome using single-molecule force spectroscopy and steered molecular dynamics simulations. The complex withstands forces of 600-750 pN, making it one of the strongest bimolecular interactions reported, equivalent to half the mechanical strength of a covalent bond. Our findings demonstrate force activation and inter-domain stabilization of the complex, and suggest that certain network components serve as mechanical effectors for maintaining network integrity. This detailed understanding of cellulosomal network components may help in the development of biocatalysts for production of fuels and chemicals from renewable plant-derived biomass.

Characterization of the Androgen-sensitive MDA-kb2 Cell Line for Assessing Complex Environmental Mixtures

EPA Science Inventory

Complex mixtures of synthetic and natural androgens and estrogens, and many other non-steroidal components are commonly released to the aquatic environment from anthropogenic sources. It is important to understand the potential interactive (i.e., additive, synergistic, antagonist...

Construction of ontology augmented networks for protein complex prediction.

PubMed

Zhang, Yijia; Lin, Hongfei; Yang, Zhihao; Wang, Jian

2013-01-01

Protein complexes are of great importance in understanding the principles of cellular organization and function. The increase in available protein-protein interaction data, gene ontology and other resources make it possible to develop computational methods for protein complex prediction. Most existing methods focus mainly on the topological structure of protein-protein interaction networks, and largely ignore the gene ontology annotation information. In this article, we constructed ontology augmented networks with protein-protein interaction data and gene ontology, which effectively unified the topological structure of protein-protein interaction networks and the similarity of gene ontology annotations into unified distance measures. After constructing ontology augmented networks, a novel method (clustering based on ontology augmented networks) was proposed to predict protein complexes, which was capable of taking into account the topological structure of the protein-protein interaction network, as well as the similarity of gene ontology annotations. Our method was applied to two different yeast protein-protein interaction datasets and predicted many well-known complexes. The experimental results showed that (i) ontology augmented networks and the unified distance measure can effectively combine the structure closeness and gene ontology annotation similarity; (ii) our method is valuable in predicting protein complexes and has higher F1 and accuracy compared to other competing methods.

Detection of Protein Complexes Based on Penalized Matrix Decomposition in a Sparse Protein⁻Protein Interaction Network.

PubMed

Cao, Buwen; Deng, Shuguang; Qin, Hua; Ding, Pingjian; Chen, Shaopeng; Li, Guanghui

2018-06-15

High-throughput technology has generated large-scale protein interaction data, which is crucial in our understanding of biological organisms. Many complex identification algorithms have been developed to determine protein complexes. However, these methods are only suitable for dense protein interaction networks, because their capabilities decrease rapidly when applied to sparse protein⁻protein interaction (PPI) networks. In this study, based on penalized matrix decomposition ( PMD ), a novel method of penalized matrix decomposition for the identification of protein complexes (i.e., PMD pc ) was developed to detect protein complexes in the human protein interaction network. This method mainly consists of three steps. First, the adjacent matrix of the protein interaction network is normalized. Second, the normalized matrix is decomposed into three factor matrices. The PMD pc method can detect protein complexes in sparse PPI networks by imposing appropriate constraints on factor matrices. Finally, the results of our method are compared with those of other methods in human PPI network. Experimental results show that our method can not only outperform classical algorithms, such as CFinder, ClusterONE, RRW, HC-PIN, and PCE-FR, but can also achieve an ideal overall performance in terms of a composite score consisting of F-measure, accuracy (ACC), and the maximum matching ratio (MMR).

Decoding the Heart through Next Generation Sequencing Approaches.

PubMed

Pawlak, Michal; Niescierowicz, Katarzyna; Winata, Cecilia Lanny

2018-06-07

: Vertebrate organs develop through a complex process which involves interaction between multiple signaling pathways at the molecular, cell, and tissue levels. Heart development is an example of such complex process which, when disrupted, results in congenital heart disease (CHD). This complexity necessitates a holistic approach which allows the visualization of genome-wide interaction networks, as opposed to assessment of limited subsets of factors. Genomics offers a powerful solution to address the problem of biological complexity by enabling the observation of molecular processes at a genome-wide scale. The emergence of next generation sequencing (NGS) technology has facilitated the expansion of genomics, increasing its output capacity and applicability in various biological disciplines. The application of NGS in various aspects of heart biology has resulted in new discoveries, generating novel insights into this field of study. Here we review the contributions of NGS technology into the understanding of heart development and its disruption reflected in CHD and discuss how emerging NGS based methodologies can contribute to the further understanding of heart repair.

Winds, Mountains, and Wildland Fire: Improved Understanding of Coupled Atmosphere-Topography-Fire Interactions Through Large-Eddy Simulation

NASA Astrophysics Data System (ADS)

Munoz-Esparza, D.; Sauer, J.; Linn, R.

2015-12-01

Anomalous and unexpected fire behavior in complex terrain continues to result in substantial loss of property and extremely dangerous conditions for firefighting field personnel. We briefly discuss proposed hypotheses of fire interactions with atmospheric flows over complex terrain that can lead to poorly-understood and potentially catastrophic scenarios. Then, our recent results of numerical investigations via large-eddy simulation of coupled atmosphere-topography-fire phenomenology with the Los Alamos National Laboratory, HiGrad-Firetec model are presented as an example of the potential for increased understanding of these complex processes. This investigation focuses on the influence of downslope surface wind enhancement through stably stratified flow over an isolated hill, and the resulting dramatic changes in fire behavior including spread rate, and intensity. Implications with respect to counter-intuitive fire behavior and extreme fire events are discussed. This work demonstrates a tremendous opportunity to immediately create safer and more effective policy for field personnel through improved predictability of atmospheric conditions over complex terrain

Moonlighting Proteins and Protein–Protein Interactions as Neurotherapeutic Targets in the G Protein-Coupled Receptor Field

PubMed Central

Fuxe, Kjell; Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Palkovits, Miklós; Tarakanov, Alexander O; Ciruela, Francisco; Agnati, Luigi F

2014-01-01

There is serious interest in understanding the dynamics of the receptor–receptor and receptor–protein interactions in space and time and their integration in GPCR heteroreceptor complexes of the CNS. Moonlighting proteins are special multifunctional proteins because they perform multiple autonomous, often unrelated, functions without partitioning into different protein domains. Moonlighting through receptor oligomerization can be operationally defined as an allosteric receptor–receptor interaction, which leads to novel functions of at least one receptor protomer. GPCR-mediated signaling is a more complicated process than previously described as every GPCR and GPCR heteroreceptor complex requires a set of G protein interacting proteins, which interacts with the receptor in an orchestrated spatio-temporal fashion. GPCR heteroreceptor complexes with allosteric receptor–receptor interactions operating through the receptor interface have become major integrative centers at the molecular level and their receptor protomers act as moonlighting proteins. The GPCR heteroreceptor complexes in the CNS have become exciting new targets for neurotherapeutics in Parkinson's disease, schizophrenia, drug addiction, and anxiety and depression opening a new field in neuropsychopharmacology. PMID:24105074

Developing Interactional Awareness in the Second Language Classroom through Teacher Self-Evaluation

ERIC Educational Resources Information Center

Walsh, Steve

2003-01-01

This paper proposes a process model of reflective practice for second language teachers, designed to facilitate a closer understanding of language use and interactive decision-making. The L2 classroom is portrayed as a dynamic and complex series of inter-related contexts, in which interaction is central to teaching and learning. An understanding…

Multidimensional approaches for studying plant defence against insects: from ecology to omics and synthetic biology.

PubMed

Barah, Pankaj; Bones, Atle M

2015-02-01

The biggest challenge for modern biology is to integrate multidisciplinary approaches towards understanding the organizational and functional complexity of biological systems at different hierarchies, starting from the subcellular molecular mechanisms (microscopic) to the functional interactions of ecological communities (macroscopic). The plant-insect interaction is a good model for this purpose with the availability of an enormous amount of information at the molecular and the ecosystem levels. Changing global climatic conditions are abruptly resetting plant-insect interactions. Integration of discretely located heterogeneous information from the ecosystem to genes and pathways will be an advantage to understand the complexity of plant-insect interactions. This review will present the recent developments in omics-based high-throughput experimental approaches, with particular emphasis on studying plant defence responses against insect attack. The review highlights the importance of using integrative systems approaches to study plant-insect interactions from the macroscopic to the microscopic level. We analyse the current efforts in generating, integrating and modelling multiomics data to understand plant-insect interaction at a systems level. As a future prospect, we highlight the growing interest in utilizing the synthetic biology platform for engineering insect-resistant plants. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The interactions of peripheral membrane proteins with biological membranes

DOE PAGES

Johs, Alexander; Whited, A. M.

2015-07-29

The interactions of peripheral proteins with membrane surfaces are critical to many biological processes, including signaling, recognition, membrane trafficking, cell division and cell structure. On a molecular level, peripheral membrane proteins can modulate lipid composition, membrane dynamics and protein-protein interactions. Biochemical and biophysical studies have shown that these interactions are in fact highly complex, dominated by several different types of interactions, and have an interdependent effect on both the protein and membrane. Here we examine three major mechanisms underlying the interactions between peripheral membrane proteins and membranes: electrostatic interactions, hydrophobic interactions, and fatty acid modification of proteins. While experimental approachesmore » continue to provide critical insights into specific interaction mechanisms, emerging bioinformatics resources and tools contribute to a systems-level picture of protein-lipid interactions. Through these recent advances, we begin to understand the pivotal role of protein-lipid interactions underlying complex biological functions at membrane interfaces.« less

What experimental approaches (eg, in vivo, in vitro, tissue retrieval) are effective in investigating the biologic effects of particles?

PubMed Central

Bostrom, Mathias; O'Keefe, Regis

2009-01-01

Understanding the complex cellular and tissue mechanisms and interactions resulting in periprosthetic osteolysis requires a number of experimental approaches, each of which has its own set of advantages and limitations. In vitro models allow for the isolation of individual cell populations and have furthered our understanding of particle-cell interactions; however, they are limited because they do not mimic the complex tissue environment in which multiple cell interactions occur. In vivo animal models investigate the tissue interactions associated with periprosthetic osteolysis, but the choice of species and whether the implant system is subjected to mechanical load or to unloaded conditions are critical in assessing whether these models can be extrapolated to the clinical condition. Rigid analysis of retrieved tissue from clinical cases of osteolysis offers a different approach to studying the biologic process of osteolysis, but it is limited in that the tissue analyzed represents the end-stage of this process and, thus, may not reflect this process adequately. PMID:18612016

What experimental approaches (eg, in vivo, in vitro, tissue retrieval) are effective in investigating the biologic effects of particles?

PubMed

Bostrom, Mathias; O'Keefe, Regis

2008-01-01

Understanding the complex cellular and tissue mechanisms and interactions resulting in periprosthetic osteolysis requires a number of experimental approaches, each of which has its own set of advantages and limitations. In vitro models allow for the isolation of individual cell populations and have furthered our understanding of particle-cell interactions; however, they are limited because they do not mimic the complex tissue environment in which multiple cell interactions occur. In vivo animal models investigate the tissue interactions associated with periprosthetic osteolysis, but the choice of species and whether the implant system is subjected to mechanical load or to unloaded conditions are critical in assessing whether these models can be extrapolated to the clinical condition. Rigid analysis of retrieved tissue from clinical cases of osteolysis offers a different approach to studying the biologic process of osteolysis, but it is limited in that the tissue analyzed represents the end-stage of this process and, thus, may not reflect this process adequately.

Tracking transcription factor mobility and interaction in Arabidopsis roots with fluorescence correlation spectroscopy

PubMed Central

Clark, Natalie M; Hinde, Elizabeth; Winter, Cara M; Fisher, Adam P; Crosti, Giuseppe; Blilou, Ikram; Gratton, Enrico; Benfey, Philip N; Sozzani, Rosangela

2016-01-01

To understand complex regulatory processes in multicellular organisms, it is critical to be able to quantitatively analyze protein movement and protein-protein interactions in time and space. During Arabidopsis development, the intercellular movement of SHORTROOT (SHR) and subsequent interaction with its downstream target SCARECROW (SCR) control root patterning and cell fate specification. However, quantitative information about the spatio-temporal dynamics of SHR movement and SHR-SCR interaction is currently unavailable. Here, we quantify parameters including SHR mobility, oligomeric state, and association with SCR using a combination of Fluorescent Correlation Spectroscopy (FCS) techniques. We then incorporate these parameters into a mathematical model of SHR and SCR, which shows that SHR reaches a steady state in minutes, while SCR and the SHR-SCR complex reach a steady-state between 18 and 24 hr. Our model reveals the timing of SHR and SCR dynamics and allows us to understand how protein movement and protein-protein stoichiometry contribute to development. DOI: http://dx.doi.org/10.7554/eLife.14770.001 PMID:27288545

Cardiorespiratory interactions in neural circulatory control in humans.

PubMed

Shamsuzzaman, A S; Somers, V K

2001-06-01

The reflex mechanisms and interactions described in this overview provide some explanation for the range of neural circulatory responses evident during changes in breathing. The effects described represent the integrated responses to activation of several reflex mechanisms, including peripheral and central chemoreflexes, arterial baroreflexes, pulmonary stretch receptors, and ventricular mechanoreceptors. These interactions occur on a dynamic basis and the transfer characteristics of any single interaction are, in all likelihood, also highly dynamic. Nevertheless, it is only by attempting to understand individual reflexes and their modulating influences that a more thorough understanding of the responses to complex phenomena such as hyperventilation, apnea, and obstructive sleep apnea can be better understood.

­Understanding Information Flow Interaction along Separable Causal Paths in Environmental Signals

NASA Astrophysics Data System (ADS)

Jiang, P.; Kumar, P.

2017-12-01

Multivariate environmental signals reflect the outcome of complex inter-dependencies, such as those in ecohydrologic systems. Transfer entropy and information partitioning approaches have been used to characterize such dependencies. However, these approaches capture net information flow occurring through a multitude of pathways involved in the interaction and as a result mask our ability to discern the causal interaction within an interested subsystem through specific pathways. We build on recent developments of momentary information transfer along causal paths proposed by Runge [2015] to develop a framework for quantifying information decomposition along separable causal paths. Momentary information transfer along causal paths captures the amount of information flow between any two variables lagged at two specific points in time. Our approach expands this concept to characterize the causal interaction in terms of synergistic, unique and redundant information flow through separable causal paths. Multivariate analysis using this novel approach reveals precise understanding of causality and feedback. We illustrate our approach with synthetic and observed time series data. We believe the proposed framework helps better delineate the internal structure of complex systems in geoscience where huge amounts of observational datasets exist, and it will also help the modeling community by providing a new way to look at the complexity of real and modeled systems. Runge, Jakob. "Quantifying information transfer and mediation along causal pathways in complex systems." Physical Review E 92.6 (2015): 062829.

Deciphering the Dynamic Interaction Profile of an Intrinsically Disordered Protein by NMR Exchange Spectroscopy.

PubMed

Delaforge, Elise; Kragelj, Jaka; Tengo, Laura; Palencia, Andrés; Milles, Sigrid; Bouvignies, Guillaume; Salvi, Nicola; Blackledge, Martin; Jensen, Malene Ringkjøbing

2018-01-24

Intrinsically disordered proteins (IDPs) display a large number of interaction modes including folding-upon-binding, binding without major structural transitions, or binding through highly dynamic, so-called fuzzy, complexes. The vast majority of experimental information about IDP binding modes have been inferred from crystal structures of proteins in complex with short peptides of IDPs. However, crystal structures provide a mainly static view of the complexes and do not give information about the conformational dynamics experienced by the IDP in the bound state. Knowledge of the dynamics of IDP complexes is of fundamental importance to understand how IDPs engage in highly specific interactions without concomitantly high binding affinity. Here, we combine rotating-frame R 1ρ , Carr-Purcell-Meiboom Gill relaxation dispersion as well as chemical exchange saturation transfer to decipher the dynamic interaction profile of an IDP in complex with its partner. We apply the approach to the dynamic signaling complex formed between the mitogen-activated protein kinase (MAPK) p38α and the intrinsically disordered regulatory domain of the MAPK kinase MKK4. Our study demonstrates that MKK4 employs a subtle combination of interaction modes in order to bind to p38α, leading to a complex displaying significantly different dynamics across the bound regions.

Systems biology approach to bioremediation

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

Chakraborty, Romy; Wu, Cindy H.; Hazen, Terry C.

2012-06-01

Bioremediation has historically been approached as a ‘black box’ in terms of our fundamental understanding. Thus it succeeds and fails, seldom without a complete understanding of why. Systems biology is an integrated research approach to study complex biological systems, by investigating interactions and networks at the molecular, cellular, community, and ecosystem level. The knowledge of these interactions within individual components is fundamental to understanding the dynamics of the ecosystem under investigation. Finally, understanding and modeling functional microbial community structure and stress responses in environments at all levels have tremendous implications for our fundamental understanding of hydrobiogeochemical processes and the potentialmore » for making bioremediation breakthroughs and illuminating the ‘black box’.« less

Patterns and processes: Subaerial lava flow morphologies: A review

NASA Astrophysics Data System (ADS)

Gregg, Tracy K. P.

2017-08-01

Most lava flows have been emplaced away from the watchful eyes of volcanologists, so there is a desire to use solidified lava-flow morphologies to reveal important information about the eruption that formed them. Our current understanding of the relationship between solidified basaltic lava morphology and the responsible eruption and emplacement processes is based on decades of fieldwork, laboratory analyses and simulations, and computer models. These studies have vastly improved our understanding of the complex interactions between the solids, liquids, and gases that comprise cooling lava flows. However, the complex interactions (at millimeter and sub-millimeter scales) between the temperature-dependent abundances of the distinct phases that comprise a lava flow and the final morphology remain challenging to model and to predict. Similarly, the complex behavior of an active pahoehoe flow, although almost ubiquitous on Earth, remains difficult to quantitatively model and precisely predict.

Sulfur-induced structural motifs on copper and gold surfaces

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

Walen, Holly

The interaction of sulfur with copper and gold surfaces plays a fundamental role in important phenomena that include coarsening of surface nanostructures, and self-assembly of alkanethiols. Here, we identify and analyze unique sulfur-induced structural motifs observed on the low-index surfaces of these two metals. We seek out these structures in an effort to better understand the fundamental interactions between these metals and sulfur that lends to the stability and favorability of metal-sulfur complexes vs. chemisorbed atomic sulfur. The experimental observations presented here—made under identical conditions—together with extensive DFT analyses, allow comparisons and insights into factors that favor the existence ofmore » metal-sulfur complexes, vs. chemisorbed atomic sulfur, on metal terraces. We believe this data will be instrumental in better understanding the complex phenomena occurring between the surfaces of coinage metals and sulfur.« less

Nonclassical Regulation of Transcription: Interchromosomal Interactions at the Malic enzyme Locus of Drosophila melanogaster

PubMed Central

Lum, Thomas E.; Merritt, Thomas J. S.

2011-01-01

Regulation of transcription can be a complex process in which many cis- and trans-interactions determine the final pattern of expression. Among these interactions are trans-interactions mediated by the pairing of homologous chromosomes. These trans-effects are wide ranging, affecting gene regulation in many species and creating complex possibilities in gene regulation. Here we describe a novel case of trans-interaction between alleles of the Malic enzyme (Men) locus in Drosophila melanogaster that results in allele-specific, non-additive gene expression. Using both empirical biochemical and predictive bioinformatic approaches, we show that the regulatory elements of one allele are capable of interacting in trans with, and modifying the expression of, the second allele. Furthermore, we show that nonlocal factors—different genetic backgrounds—are capable of significant interactions with individual Men alleles, suggesting that these trans-effects can be modified by both locally and distantly acting elements. In sum, these results emphasize the complexity of gene regulation and the need to understand both small- and large-scale interactions as more complete models of the role of trans-interactions in gene regulation are developed. PMID:21900270

Confronting Analytical Dilemmas for Understanding Complex Human Interactions in Design-Based Research from a Cultural-Historical Activity Theory (CHAT) Framework

ERIC Educational Resources Information Center

Yamagata-Lynch, Lisa C.

2007-01-01

Understanding human activity in real-world situations often involves complicated data collection, analysis, and presentation methods. This article discusses how Cultural-Historical Activity Theory (CHAT) can inform design-based research practices that focus on understanding activity in real-world situations. I provide a sample data set with…

Levels of behavioral organization and the evolution of division of labor

NASA Astrophysics Data System (ADS)

Page, Robert E.; Erber, Joachim

2002-03-01

The major features of insect societies that fascinate biologists are the self-sacrificing altruism expressed by colony members, the complex division of labor, and the tremendous plasticity demonstrated in the face of changing environments. The social behavior of insects is a result of complex interactions at different levels of biological organization. Genes give rise to proteins and peptides that build the nervous and muscular systems, regulate their own synthesis, interact with each other, and affect the behavior of individuals. Social behavior emerges from the complex interactions of individuals that are themselves far removed from the direct effects of the genes. In order to understand how social organization evolves, we must understand the mechanisms that link the different levels of organization. In this review, we discuss how behavior is influenced by genes and the neural system and how social behavior emerges from the behavioral activities of individuals. We show how different levels of organization share common features and are linked through common mechanisms. We focus on the behavior of the honey bee, the best studied of all social insects.

Mathematical approach to nonlocal interactions using a reaction-diffusion system.

PubMed

Tanaka, Yoshitaro; Yamamoto, Hiroko; Ninomiya, Hirokazu

2017-06-01

In recent years, spatial long range interactions during developmental processes have been introduced as a result of the integration of microscopic information, such as molecular events and signaling networks. They are often called nonlocal interactions. If the profile of a nonlocal interaction is determined by experiments, we can easily investigate how patterns generate by numerical simulations without detailed microscopic events. Thus, nonlocal interactions are useful tools to understand complex biosystems. However, nonlocal interactions are often inconvenient for observing specific mechanisms because of the integration of information. Accordingly, we proposed a new method that could convert nonlocal interactions into a reaction-diffusion system with auxiliary unknown variables. In this review, by introducing biological and mathematical studies related to nonlocal interactions, we will present the heuristic understanding of nonlocal interactions using a reaction-diffusion system. © 2017 Japanese Society of Developmental Biologists.

ShapeShop: Towards Understanding Deep Learning Representations via Interactive Experimentation

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

Hohman, Frederick M.; Hodas, Nathan O.; Chau, Duen Horng

Deep learning is the driving force behind many recent technologies; however, deep neural networks are often viewed as “black-boxes” due to their internal complexity that is hard to understand. Little research focuses on helping people explore and understand the relationship between a user’s data and the learned representations in deep learning models. We present our ongoing work, ShapeShop, an interactive system for visualizing and understanding what semantics a neural network model has learned. Built using standard web technologies, ShapeShop allows users to experiment with and compare deep learning models to help explore the robustness of image classifiers.

Small- and Large-Effect Quantitative Trait Locus Interactions Underlie Variation in Yeast Sporulation Efficiency

PubMed Central

Lorenz, Kim; Cohen, Barak A.

2012-01-01

Quantitative trait loci (QTL) with small effects on phenotypic variation can be difficult to detect and analyze. Because of this a large fraction of the genetic architecture of many complex traits is not well understood. Here we use sporulation efficiency in Saccharomyces cerevisiae as a model complex trait to identify and study small-effect QTL. In crosses where the large-effect quantitative trait nucleotides (QTN) have been genetically fixed we identify small-effect QTL that explain approximately half of the remaining variation not explained by the major effects. We find that small-effect QTL are often physically linked to large-effect QTL and that there are extensive genetic interactions between small- and large-effect QTL. A more complete understanding of quantitative traits will require a better understanding of the numbers, effect sizes, and genetic interactions of small-effect QTL. PMID:22942125

Understanding the value of mixed methods research: the Children’s Safety Initiative-Emergency Medical Services

PubMed Central

Hansen, Matthew; O’Brien, Kerth; Meckler, Garth; Chang, Anna Marie; Guise, Jeanne-Marie

2016-01-01

Mixed methods research has significant potential to broaden the scope of emergency care and specifically emergency medical services investigation. Mixed methods studies involve the coordinated use of qualitative and quantitative research approaches to gain a fuller understanding of practice. By combining what is learnt from multiple methods, these approaches can help to characterise complex healthcare systems, identify the mechanisms of complex problems such as medical errors and understand aspects of human interaction such as communication, behaviour and team performance. Mixed methods approaches may be particularly useful for out-of-hospital care researchers because care is provided in complex systems where equipment, interpersonal interactions, societal norms, environment and other factors influence patient outcomes. The overall objectives of this paper are to (1) introduce the fundamental concepts and approaches of mixed methods research and (2) describe the interrelation and complementary features of the quantitative and qualitative components of mixed methods studies using specific examples from the Children’s Safety Initiative-Emergency Medical Services (CSI-EMS), a large National Institutes of Health-funded research project conducted in the USA. PMID:26949970

Dynamic Plant-Plant-Herbivore Interactions Govern Plant Growth-Defence Integration.

PubMed

de Vries, Jorad; Evers, Jochem B; Poelman, Erik H

2017-04-01

Plants downregulate their defences against insect herbivores upon impending competition for light. This has long been considered a resource trade-off, but recent advances in plant physiology and ecology suggest this mechanism is more complex. Here we propose that to understand why plants regulate and balance growth and defence, the complex dynamics in plant-plant competition and plant-herbivore interactions needs to be considered. Induced growth-defence responses affect plant competition and herbivore colonisation in space and time, which has consequences for the adaptive value of these responses. Assessing these complex interactions strongly benefits from advanced modelling tools that can model multitrophic interactions in space and time. Such an exercise will allow a critical re-evaluation why and how plants integrate defence and competition for light. Copyright © 2016 Elsevier Ltd. All rights reserved.

Root Systems Biology: Integrative Modeling across Scales, from Gene Regulatory Networks to the Rhizosphere1

PubMed Central

Hill, Kristine; Porco, Silvana; Lobet, Guillaume; Zappala, Susan; Mooney, Sacha; Draye, Xavier; Bennett, Malcolm J.

2013-01-01

Genetic and genomic approaches in model organisms have advanced our understanding of root biology over the last decade. Recently, however, systems biology and modeling have emerged as important approaches, as our understanding of root regulatory pathways has become more complex and interpreting pathway outputs has become less intuitive. To relate root genotype to phenotype, we must move beyond the examination of interactions at the genetic network scale and employ multiscale modeling approaches to predict emergent properties at the tissue, organ, organism, and rhizosphere scales. Understanding the underlying biological mechanisms and the complex interplay between systems at these different scales requires an integrative approach. Here, we describe examples of such approaches and discuss the merits of developing models to span multiple scales, from network to population levels, and to address dynamic interactions between plants and their environment. PMID:24143806

The promise of genomics in the study of plant-pollinator interactions

PubMed Central

2013-01-01

Flowers exist in exceedingly complex fitness landscapes, in which subtle variation in each trait can affect the pollinators, herbivores and pleiotropically linked traits in other plant tissues. A whole-genome approach to flower evolution will help our understanding of plant-pollinator interactions. PMID:23796166

Connecting the Human Variome Project to nutrigenomics.

PubMed

Kaput, Jim; Evelo, Chris T; Perozzi, Giuditta; van Ommen, Ben; Cotton, Richard

2010-12-01

Nutrigenomics is the science of analyzing and understanding gene-nutrient interactions, which because of the genetic heterogeneity, varying degrees of interaction among gene products, and the environmental diversity is a complex science. Although much knowledge of human diversity has been accumulated, estimates suggest that ~90% of genetic variation has not yet been characterized. Identification of the DNA sequence variants that contribute to nutrition-related disease risk is essential for developing a better understanding of the complex causes of disease in humans, including nutrition-related disease. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) is an international effort to systematically identify genes, their mutations, and their variants associated with phenotypic variability and indications of human disease or phenotype. Since nutrigenomic research uses genetic information in the design and analysis of experiments, the HVP is an essential collaborator for ongoing studies of gene-nutrient interactions. With the advent of next generation sequencing methodologies and the understanding of the undiscovered variation in human genomes, the nutrigenomic community will be generating novel sequence data and results. The guidelines and practices of the HVP can guide and harmonize these efforts.

Connecting the Human Variome Project to nutrigenomics

PubMed Central

Evelo, Chris T.; Perozzi, Giuditta; van Ommen, Ben; Cotton, Richard

2010-01-01

Nutrigenomics is the science of analyzing and understanding gene–nutrient interactions, which because of the genetic heterogeneity, varying degrees of interaction among gene products, and the environmental diversity is a complex science. Although much knowledge of human diversity has been accumulated, estimates suggest that ~90% of genetic variation has not yet been characterized. Identification of the DNA sequence variants that contribute to nutrition-related disease risk is essential for developing a better understanding of the complex causes of disease in humans, including nutrition-related disease. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) is an international effort to systematically identify genes, their mutations, and their variants associated with phenotypic variability and indications of human disease or phenotype. Since nutrigenomic research uses genetic information in the design and analysis of experiments, the HVP is an essential collaborator for ongoing studies of gene–nutrient interactions. With the advent of next generation sequencing methodologies and the understanding of the undiscovered variation in human genomes, the nutrigenomic community will be generating novel sequence data and results. The guidelines and practices of the HVP can guide and harmonize these efforts. PMID:28300226

Understanding interfirm relationships in business ecosystems with interactive visualization.

PubMed

Basole, Rahul C; Clear, Trustin; Hu, Mengdie; Mehrotra, Harshit; Stasko, John

2013-12-01

Business ecosystems are characterized by large, complex, and global networks of firms, often from many different market segments, all collaborating, partnering, and competing to create and deliver new products and services. Given the rapidly increasing scale, complexity, and rate of change of business ecosystems, as well as economic and competitive pressures, analysts are faced with the formidable task of quickly understanding the fundamental characteristics of these interfirm networks. Existing tools, however, are predominantly query- or list-centric with limited interactive, exploratory capabilities. Guided by a field study of corporate analysts, we have designed and implemented dotlink360, an interactive visualization system that provides capabilities to gain systemic insight into the compositional, temporal, and connective characteristics of business ecosystems. dotlink360 consists of novel, multiple connected views enabling the analyst to explore, discover, and understand interfirm networks for a focal firm, specific market segments or countries, and the entire business ecosystem. System evaluation by a small group of prototypical users shows supporting evidence of the benefits of our approach. This design study contributes to the relatively unexplored, but promising area of exploratory information visualization in market research and business strategy.

Waves associated to COMPLEX EVENTS observed by STEREO

NASA Astrophysics Data System (ADS)

Siu Tapia, A. L.; Blanco-Cano, X.; Kajdic, P.; Aguilar-Rodriguez, E.; Russell, C. T.; Jian, L. K.; Luhmann, J. G.

2012-12-01

Complex Events are formed by two or more large-scale solar wind structures which interact in space. Typical cases are interactions of: (i) a Magnetic Cloud/Interplanetary Coronal Mass Ejection (MC/ICME) with another MC/ICME transient; and (ii) an ICME followed by a Stream Interaction Region (SIR). Complex Events are of importance for space weather studies and studying them can enhance our understanding of collisionless plasma physics. Some of these structures can produce or enhance southward magnetic fields, a key factor in geomagnetic storm generation. Using data from the STEREO mission during the years 2006-2011, we found 17 Complex Events preceded by a shock wave. We use magnetic field and plasma data to study the micro-scale structure of the shocks, and the waves associated to these shocks and within Complex Events structures. To determine wave characteristics we perform Power Spectra and Minimum Variance Analysis. We also use PLASTIC WAP protons data to study foreshock extensions and the relationship between Complex Regions and particle acceleration to suprathermal energies.

Facilitating and Learning at the Edge of Chaos: Expanding the Context of Experiential Education.

ERIC Educational Resources Information Center

Oekerman, Carl

Significant recent discoveries within a number of scientific disciplines, collectively referred to as the science of complexity, are creating a major shift in how human beings understand the complex, adaptive systems that make up the world. A complex adaptive system consists of networks of large numbers of agents that interact with each other and…

Noninvasive imaging of protein-protein interactions in living organisms.

PubMed

Haberkorn, Uwe; Altmann, Annette

2003-06-01

Genomic research is expected to generate new types of complex observational data, changing the types of experiments as well as our understanding of biological processes. The investigation and definition of relationships among proteins is essential for understanding the function of each gene and the mechanisms of biological processes that specific genes are involved in. Recently, a study by Paulmurugan et al. demonstrated a tool for in vivo noninvasive imaging of protein-protein interactions and intracellular networks.

Complex adaptive systems: A new approach for understanding health practices.

PubMed

Gomersall, Tim

2018-06-22

This article explores the potential of complex adaptive systems theory to inform behaviour change research. A complex adaptive system describes a collection of heterogeneous agents interacting within a particular context, adapting to each other's actions. In practical terms, this implies that behaviour change is 1) socially and culturally situated; 2) highly sensitive to small baseline differences in individuals, groups, and intervention components; and 3) determined by multiple components interacting "chaotically". Two approaches to studying complex adaptive systems are briefly reviewed. Agent-based modelling is a computer simulation technique that allows researchers to investigate "what if" questions in a virtual environment. Applied qualitative research techniques, on the other hand, offer a way to examine what happens when an intervention is pursued in real-time, and to identify the sorts of rules and assumptions governing social action. Although these represent very different approaches to complexity, there may be scope for mixing these methods - for example, by grounding models in insights derived from qualitative fieldwork. Finally, I will argue that the concept of complex adaptive systems offers one opportunity to gain a deepened understanding of health-related practices, and to examine the social psychological processes that produce health-promoting or damaging actions.

Electrophysiological Correlates of Reading the Single- and Interactive-Mind

PubMed Central

Wang, Yi-Wen; Zheng, Yu-Wei; Lin, Chong-De; Wu, Jie; Shen, De-Li

2011-01-01

Understanding minds is the cognitive basis of successful social interaction. In everyday life, human mental activity often happens at the moment of social interaction among two or multiple persons instead of only one-person. Understanding the interactive mind of two- or multi-person is more complex and higher than understanding the single-person mind in the hierarchical structure of theory of mind. Understanding the interactive mind maybe differentiate from understanding the single mind. In order to examine the dissociative electrophysiological correlates of reading the single mind and reading the interactive mind, the 64 channels event-related potentials were recorded while 16 normal adults were observing three kinds of Chinese idioms depicted physical scenes, one-person with mental activity, and two- or multi-person with mental interaction. After the equivalent N400, in the 500- to 700-ms epoch, the mean amplitudes of late positive component (LPC) over frontal for reading the single mind and reading the interactive mind were significantly more positive than for physical representation, while there was no difference between the former two. In the 700- to 800-ms epoch, the mean amplitudes of LPC over frontal–central for reading the interactive mind were more positive than for reading the single mind and physical representation, while there was no difference between the latter two. The present study provides electrophysiological signature of the dissociations between reading the single mind and reading the interactive mind. PMID:21845178

Molecular mechanics and dynamics studies on the interaction of gallic acid with collagen-like peptides

NASA Astrophysics Data System (ADS)

Madhan, B.; Thanikaivelan, P.; Subramanian, V.; Raghava Rao, J.; Unni Nair, Balachandran; Ramasami, T.

2001-10-01

Molecular modelling approaches have been used to understand the interaction of collagen-like peptides with gallic acid, which mimic vegetable tanning processes involved in protein stabilization. Several interaction sites have been identified and the binding energies of the complexes have been calculated. The calculated binding energies for various geometries are in the range 6-13 kcal/mol. It is found that some complexes exhibit hydrogen bonding, and electrostatic interaction plays a dominant role in the stabilization of the peptide by gallic acid. The π-OH type of interaction is also observed in the peptide stabilization. Molecular dynamics (MD) simulation for 600 ps revealed the possibility of hydrogen bonding between the collagen-like peptide and gallic acid.

Rapid, Optimized Interactomic Screening

PubMed Central

Hakhverdyan, Zhanna; Domanski, Michal; Hough, Loren; Oroskar, Asha A.; Oroskar, Anil R.; Keegan, Sarah; Dilworth, David J.; Molloy, Kelly R.; Sherman, Vadim; Aitchison, John D.; Fenyö, David; Chait, Brian T.; Jensen, Torben Heick; Rout, Michael P.; LaCava, John

2015-01-01

We must reliably map the interactomes of cellular macromolecular complexes in order to fully explore and understand biological systems. However, there are no methods to accurately predict how to capture a given macromolecular complex with its physiological binding partners. Here, we present a screen that comprehensively explores the parameters affecting the stability of interactions in affinity-captured complexes, enabling the discovery of physiological binding partners and the elucidation of their functional interactions in unparalleled detail. We have implemented this screen on several macromolecular complexes from a variety of organisms, revealing novel profiles even for well-studied proteins. Our approach is robust, economical and automatable, providing an inroad to the rigorous, systematic dissection of cellular interactomes. PMID:25938370

Investigation of the heparin-thrombin interaction by dynamic force spectroscopy.

PubMed

Wang, Congzhou; Jin, Yingzi; Desai, Umesh R; Yadavalli, Vamsi K

2015-06-01

The interaction between heparin and thrombin is a vital step in the blood (anti)coagulation process. Unraveling the molecular basis of the interactions is therefore extremely important in understanding the mechanisms of this complex biological process. In this study, we use a combination of an efficient thiolation chemistry of heparin, a self-assembled monolayer-based single molecule platform, and a dynamic force spectroscopy to provide new insights into the heparin-thrombin interaction from an energy viewpoint at the molecular scale. Well-separated single molecules of heparin covalently attached to mixed self-assembled monolayers are demonstrated, whereby interaction forces with thrombin can be measured via atomic force microscopy-based spectroscopy. Further these interactions are studied at different loading rates and salt concentrations to directly obtain kinetic parameters. An increase in the loading rate shows a higher interaction force between the heparin and thrombin, which can be directly linked to the kinetic dissociation rate constant (koff). The stability of the heparin/thrombin complex decreased with increasing NaCl concentration such that the off-rate was found to be driven primarily by non-ionic forces. These results contribute to understanding the role of specific and nonspecific forces that drive heparin-thrombin interactions under applied force or flow conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

Understanding the structure

Treesearch

David J. Nowak

1994-01-01

Urban forests are complex ecosystems created by the interaction of anthropogenic and natural processes. One key to better management of these systems is to understand urban forest structure and its relationship to forest functions. Through sampling and inventories, urban foresters often obtain structural information (e.g., numbers, location, size, and condition) on...

Using Remote Sensing Data to Constrain Models of Fault Interactions and Plate Boundary Deformation

NASA Astrophysics Data System (ADS)

Glasscoe, M. T.; Donnellan, A.; Lyzenga, G. A.; Parker, J. W.; Milliner, C. W. D.

2016-12-01

Determining the distribution of slip and behavior of fault interactions at plate boundaries is a complex problem. Field and remotely sensed data often lack the necessary coverage to fully resolve fault behavior. However, realistic physical models may be used to more accurately characterize the complex behavior of faults constrained with observed data, such as GPS, InSAR, and SfM. These results will improve the utility of using combined models and data to estimate earthquake potential and characterize plate boundary behavior. Plate boundary faults exhibit complex behavior, with partitioned slip and distributed deformation. To investigate what fraction of slip becomes distributed deformation off major faults, we examine a model fault embedded within a damage zone of reduced elastic rigidity that narrows with depth and forward model the slip and resulting surface deformation. The fault segments and slip distributions are modeled using the JPL GeoFEST software. GeoFEST (Geophysical Finite Element Simulation Tool) is a two- and three-dimensional finite element software package for modeling solid stress and strain in geophysical and other continuum domain applications [Lyzenga, et al., 2000; Glasscoe, et al., 2004; Parker, et al., 2008, 2010]. New methods to advance geohazards research using computer simulations and remotely sensed observations for model validation are required to understand fault slip, the complex nature of fault interaction and plate boundary deformation. These models help enhance our understanding of the underlying processes, such as transient deformation and fault creep, and can aid in developing observation strategies for sUAV, airborne, and upcoming satellite missions seeking to determine how faults behave and interact and assess their associated hazard. Models will also help to characterize this behavior, which will enable improvements in hazard estimation. Validating the model results against remotely sensed observations will allow us to better constrain fault zone rheology and physical properties, having implications for the overall understanding of earthquake physics, fault interactions, plate boundary deformation and earthquake hazard, preparedness and risk reduction.

Characterization of the Androgen-sensitive MDA-kb2 Cell Line for Assessing Complex Environmental Mixtures, Presentation

EPA Science Inventory

Synthetic and natural steroidal androgens and estrogens and many other non-steroidal endocrine-active compounds commonly occur as complex mixtures in aquatic environments. It is important to understand the potential interactive effects of these mixtures to properly assess their r...

Teachers' Beliefs and Practices: A Dynamic and Complex Relationship

ERIC Educational Resources Information Center

Zheng, Hongying

2013-01-01

Research on teachers' beliefs has provided useful insights into understanding processes of teaching. However, no research has explored teachers' beliefs as a system nor have researchers investigated the substance of interactions between teachers' beliefs, practices and context. Therefore, the author adopts complexity theory to explore the features…

The Complex Experience of Learning to Do Research

ERIC Educational Resources Information Center

Emo, Kenneth; Emo, Wendy; Kimn, Jung-Han; Gent, Stephen

2015-01-01

This article examines how student learning is a product of the experiential interaction between person and environment. We draw from the theoretical perspective of complexity to shed light on the emergent, adaptive, and unpredictable nature of students' learning experiences. To understand the relationship between the environment and the student…

Parental Cognitions, Parental Behavior, and the Child's Understanding of the Parent-Child Relationship.

ERIC Educational Resources Information Center

Dekovic, Maja; And Others

1991-01-01

Studied the relationship of parental reasoning complexity to parental behavior during parent-child interactions, and the effect of this relationship on children's social cognitions. Results indicate that parental reasoning complexity is related to parental behaviors of restrictive control, authoritative control, and support, which, in turn, are…

Invasion complexity at large spatial scales is an emergent property of interactions among landscape characteristics and invader traits

USDA-ARS?s Scientific Manuscript database

Understanding the potential for invasive spread is an important consideration for novel agricultural species that may be translocated or introduced into new regions. However, estimating invasion risks remains a challenging problem, particularly in the context of real, complex landscapes. There is ...

Sight Application Analysis Tool

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

Bronevetsky, G.

2014-09-17

The scale and complexity of scientific applications makes it very difficult to optimize, debug and extend them to support new capabilities. We have developed a tool that supports developers’ efforts to understand the logical flow of their applications and interactions between application components and hardware in a way that scales with application complexity and parallelism.

Rheological characterization of solutions and thin films made from amylose-hexadecylammonium chloride inclusion complexes and polyvinyl alcohol

USDA-ARS?s Scientific Manuscript database

The rheological properties of aqueous solutions and films made from blends of polyvinyl alcohol (PVOH) and amylose-hexadecylammonium chloride inclusion complexes (Hex-Am) were investigated to better understand the polymer interactions and processing parameters. Aqueous solutions of Hex-Am displayed ...

Do Haptic Representations Help Complex Molecular Learning?

ERIC Educational Resources Information Center

Bivall, Petter; Ainsworth, Shaaron; Tibell, Lena A. E.

2011-01-01

This study explored whether adding a haptic interface (that provides users with somatosensory information about virtual objects by force and tactile feedback) to a three-dimensional (3D) chemical model enhanced students' understanding of complex molecular interactions. Two modes of the model were compared in a between-groups pre- and posttest…

The human gut microbiota and its interactive connections to diet.

PubMed

Milani, C; Ferrario, C; Turroni, F; Duranti, S; Mangifesta, M; van Sinderen, D; Ventura, M

2016-10-01

The microbiota of the gastrointestinal tract plays an important role in human health. In addition to their metabolic interactions with dietary constituents, gut bacteria may also be involved in more complex host interactions, such as modulation of the immune system. Furthermore, the composition of the gut microbiota may be important in reducing the risk of contracting particular gut infections. Changes in the microbiota during an individual's lifespan are accompanied by modifications in multiple health parameters, and such observations have prompted intense scientific efforts aiming to understand the complex interactions between the microbiota and its human host, as well as how this may be influenced by diet. © 2016 The British Dietetic Association Ltd.

Characterization of known protein complexes using k-connectivity and other topological measures

PubMed Central

Gallagher, Suzanne R; Goldberg, Debra S

2015-01-01

Many protein complexes are densely packed, so proteins within complexes often interact with several other proteins in the complex. Steric constraints prevent most proteins from simultaneously binding more than a handful of other proteins, regardless of the number of proteins in the complex. Because of this, as complex size increases, several measures of the complex decrease within protein-protein interaction networks. However, k-connectivity, the number of vertices or edges that need to be removed in order to disconnect a graph, may be consistently high for protein complexes. The property of k-connectivity has been little used previously in the investigation of protein-protein interactions. To understand the discriminative power of k-connectivity and other topological measures for identifying unknown protein complexes, we characterized these properties in known Saccharomyces cerevisiae protein complexes in networks generated both from highly accurate X-ray crystallography experiments which give an accurate model of each complex, and also as the complexes appear in high-throughput yeast 2-hybrid studies in which new complexes may be discovered. We also computed these properties for appropriate random subgraphs.We found that clustering coefficient, mutual clustering coefficient, and k-connectivity are better indicators of known protein complexes than edge density, degree, or betweenness. This suggests new directions for future protein complex-finding algorithms. PMID:26913183

An individual-based process model to simulate landscape-scale forest ecosystem dynamics

Treesearch

Rupert Seidl; Werner Rammer; Robert M. Scheller; Thomas Spies

2012-01-01

Forest ecosystem dynamics emerges from nonlinear interactions between adaptive biotic agents (i.e., individual trees) and their relationship with a spatially and temporally heterogeneous abiotic environment. Understanding and predicting the dynamics resulting from these complex interactions is crucial for the sustainable stewardship of ecosystems, particularly in the...

The functional interactome landscape of the human histone deacetylase family

PubMed Central

Joshi, Preeti; Greco, Todd M; Guise, Amanda J; Luo, Yang; Yu, Fang; Nesvizhskii, Alexey I; Cristea, Ileana M

2013-01-01

Histone deacetylases (HDACs) are a diverse family of essential transcriptional regulatory enzymes, that function through the spatial and temporal recruitment of protein complexes. As the composition and regulation of HDAC complexes are only partially characterized, we built the first global protein interaction network for all 11 human HDACs in T cells. Integrating fluorescence microscopy, immunoaffinity purifications, quantitative mass spectrometry, and bioinformatics, we identified over 200 unreported interactions for both well-characterized and lesser-studied HDACs, a subset of which were validated by orthogonal approaches. We establish HDAC11 as a member of the survival of motor neuron complex and pinpoint a functional role in mRNA splicing. We designed a complementary label-free and metabolic-labeling mass spectrometry-based proteomics strategy for profiling interaction stability among different HDAC classes, revealing that HDAC1 interactions within chromatin-remodeling complexes are largely stable, while transcription factors preferentially exist in rapid equilibrium. Overall, this study represents a valuable resource for investigating HDAC functions in health and disease, encompassing emerging themes of HDAC regulation in cell cycle and RNA processing and a deeper functional understanding of HDAC complex stability. PMID:23752268

The malaria parasite RhopH protein complex interacts with erythrocyte calmyrin identified from a comprehensive erythrocyte protein library.

PubMed

Miura, Toyokazu; Takeo, Satoru; Ntege, Edward H; Otsuki, Hitoshi; Sawasaki, Tatsuya; Ishino, Tomoko; Takashima, Eizo; Tsuboi, Takafumi

2018-06-02

Malaria merozoite apical organelles; microneme and rhoptry secreted proteins play functional roles during and following invasion of host erythrocytes. Among numerous proteins, the rhoptries discharge high molecular weight proteins known as RhopH complex. Recent reports suggest that the RhopH complex is essential for growth and survival of the malaria parasite within erythrocytes. However, an in-depth understanding of the host-parasite molecular interactions is indispensable. Here we utilized a comprehensive mouse erythrocyte protein library consisting of 443 proteins produced by a wheat germ cell-free system, combined with AlphaScreen technology to identify mouse erythrocyte calmyrin as an interacting molecule of the rodent malaria parasite Plasmodium yoelii RhopH complex (PyRhopH). The PyRhopH interaction was dependent on the calmyrin N-terminus and divalent cation capacity. The finding unveils a recommendable and invaluable usefulness of our comprehensive mouse erythrocyte protein library together with the AlphaScreen technology in investigating a wide-range of host-parasite molecular interactions. Copyright © 2018 Elsevier Inc. All rights reserved.

DNAproDB: an interactive tool for structural analysis of DNA–protein complexes

PubMed Central

Sagendorf, Jared M.

2017-01-01

Abstract Many biological processes are mediated by complex interactions between DNA and proteins. Transcription factors, various polymerases, nucleases and histones recognize and bind DNA with different levels of binding specificity. To understand the physical mechanisms that allow proteins to recognize DNA and achieve their biological functions, it is important to analyze structures of DNA–protein complexes in detail. DNAproDB is a web-based interactive tool designed to help researchers study these complexes. DNAproDB provides an automated structure-processing pipeline that extracts structural features from DNA–protein complexes. The extracted features are organized in structured data files, which are easily parsed with any programming language or viewed in a browser. We processed a large number of DNA–protein complexes retrieved from the Protein Data Bank and created the DNAproDB database to store this data. Users can search the database by combining features of the DNA, protein or DNA–protein interactions at the interface. Additionally, users can upload their own structures for processing privately and securely. DNAproDB provides several interactive and customizable tools for creating visualizations of the DNA–protein interface at different levels of abstraction that can be exported as high quality figures. All functionality is documented and freely accessible at http://dnaprodb.usc.edu. PMID:28431131

Developing interprofessional education online: An ecological systems theory analysis.

PubMed

Bluteau, Patricia; Clouder, Lynn; Cureton, Debra

2017-07-01

This article relates the findings of a discourse analysis of an online asynchronous interprofessional learning initiative involving two UK universities. The impact of the initiative is traced over three intensive periods of online interaction, each of several-weeks duration occurring over a three-year period, through an analysis of a random sample of discussion forum threads. The corpus of rich data drawn from the forums is interpreted using ecological systems theory, which highlights the complexity of interaction of individual, social and cultural elements. Ecological systems theory adopts a life course approach to understand how development occurs through processes of progressively more complex reciprocal interaction between people and their environment. This lens provides a novel approach for analysis and interpretation of findings with respect to the impact of pre-registration interprofessional education and the interaction between the individual and their social and cultural contexts as they progress through 3/4 years of their programmes. Development is mapped over time (the chronosystem) to highlight the complexity of interaction across microsystems (individual), mesosystems (curriculum and institutional/care settings), exosystems (community/wider local context), and macrosystems (national context and culture). This article illustrates the intricacies of students' interprofessional development over time and the interactive effects of social ecological components in terms of professional knowledge and understanding, wider appreciation of health and social care culture and identity work. The implications for contemporary pre-registration interprofessional education and the usefulness and applicability of ecological systems theory for future research and development are considered.

Using Activity Theory to Understand Learning Design Requirements of Patient Self-Management Environments

ERIC Educational Resources Information Center

Schaffer, Scott P.; Reyes, Lisette; Kim, Hannah; Collins, Bart

2010-01-01

Learning designs aimed at supporting transformational change could significantly benefit from the adoption of socio-historical and socio-cultural analysis approaches. Such systemic perspectives are gaining more importance in education as they facilitate understanding of complex interactions between learning environments and human activity. The…

PAMPs, PRRs, effectors and R-genes associated with citrus–pathogen interactions

PubMed Central

Dalio, Ronaldo J. D.; Magalhães, Diogo M.; Rodrigues, Carolina M.; Arena, Gabriella D.; Oliveira, Tiago S.; Souza-Neto, Reinaldo R.; Picchi, Simone C.; Martins, Paula M. M.; Santos, Paulo J. C.; Maximo, Heros J.; Pacheco, Inaiara S.; De Souza, Alessandra A.

2017-01-01

Abstract Background Recent application of molecular-based technologies has considerably advanced our understanding of complex processes in plant–pathogen interactions and their key components such as PAMPs, PRRs, effectors and R-genes. To develop novel control strategies for disease prevention in citrus, it is essential to expand and consolidate our knowledge of the molecular interaction of citrus plants with their pathogens. Scope This review provides an overview of our understanding of citrus plant immunity, focusing on the molecular mechanisms involved in the interactions with viruses, bacteria, fungi, oomycetes and vectors related to the following diseases: tristeza, psorosis, citrus variegated chlorosis, citrus canker, huanglongbing, brown spot, post-bloom, anthracnose, gummosis and citrus root rot. PMID:28065920

Dynamics of analyst forecasts and emergence of complexity: Role of information disparity

PubMed Central

Ahn, Kwangwon

2017-01-01

We report complex phenomena arising among financial analysts, who gather information and generate investment advice, and elucidate them with the help of a theoretical model. Understanding how analysts form their forecasts is important in better understanding the financial market. Carrying out big-data analysis of the analyst forecast data from I/B/E/S for nearly thirty years, we find skew distributions as evidence for emergence of complexity, and show how information asymmetry or disparity affects financial analysts’ forming their forecasts. Here regulations, information dissemination throughout a fiscal year, and interactions among financial analysts are regarded as the proxy for a lower level of information disparity. It is found that financial analysts with better access to information display contrasting behaviors: a few analysts become bolder and issue forecasts independent of other forecasts while the majority of analysts issue more accurate forecasts and flock to each other. Main body of our sample of optimistic forecasts fits a log-normal distribution, with the tail displaying a power law. Based on the Yule process, we propose a model for the dynamics of issuing forecasts, incorporating interactions between analysts. Explaining nicely empirical data on analyst forecasts, this provides an appealing instance of understanding social phenomena in the perspective of complex systems. PMID:28498831

Molecular dynamics simulations and statistical coupling analysis reveal functional coevolution network of oncogenic mutations in the CDKN2A-CDK6 complex.

PubMed

Wang, Jingwen; Zhao, Yuqi; Wang, Yanjie; Huang, Jingfei

2013-01-16

Coevolution between proteins is crucial for understanding protein-protein interaction. Simultaneous changes allow a protein complex to maintain its overall structural-functional integrity. In this study, we combined statistical coupling analysis (SCA) and molecular dynamics simulations on the CDK6-CDKN2A protein complex to evaluate coevolution between proteins. We reconstructed an inter-protein residue coevolution network, consisting of 37 residues and 37 interactions. It shows that most of the coevolved residue pairs are spatially proximal. When the mutations happened, the stable local structures were broken up and thus the protein interaction was decreased or inhibited, with a following increased risk of melanoma. The identification of inter-protein coevolved residues in the CDK6-CDKN2A complex can be helpful for designing protein engineering experiments. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Modeling synthetic lethality

PubMed Central

Le Meur, Nolwenn; Gentleman, Robert

2008-01-01

Background Synthetic lethality defines a genetic interaction where the combination of mutations in two or more genes leads to cell death. The implications of synthetic lethal screens have been discussed in the context of drug development as synthetic lethal pairs could be used to selectively kill cancer cells, but leave normal cells relatively unharmed. A challenge is to assess genome-wide experimental data and integrate the results to better understand the underlying biological processes. We propose statistical and computational tools that can be used to find relationships between synthetic lethality and cellular organizational units. Results In Saccharomyces cerevisiae, we identified multi-protein complexes and pairs of multi-protein complexes that share an unusually high number of synthetic genetic interactions. As previously predicted, we found that synthetic lethality can arise from subunits of an essential multi-protein complex or between pairs of multi-protein complexes. Finally, using multi-protein complexes allowed us to take into account the pleiotropic nature of the gene products. Conclusions Modeling synthetic lethality using current estimates of the yeast interactome is an efficient approach to disentangle some of the complex molecular interactions that drive a cell. Our model in conjunction with applied statistical methods and computational methods provides new tools to better characterize synthetic genetic interactions. PMID:18789146

Models of S/π interactions in protein structures: Comparison of the H2S–benzene complex with PDB data

PubMed Central

Ringer, Ashley L.; Senenko, Anastasia; Sherrill, C. David

2007-01-01

S/π interactions are prevalent in biochemistry and play an important role in protein folding and stabilization. Geometries of cysteine/aromatic interactions found in crystal structures from the Brookhaven Protein Data Bank (PDB) are analyzed and compared with the equilibrium configurations predicted by high-level quantum mechanical results for the H2S–benzene complex. A correlation is observed between the energetically favorable configurations on the quantum mechanical potential energy surface of the H2S–benzene model and the cysteine/aromatic configurations most frequently found in crystal structures of the PDB. In contrast to some previous PDB analyses, configurations with the sulfur over the aromatic ring are found to be the most important. Our results suggest that accurate quantum computations on models of noncovalent interactions may be helpful in understanding the structures of proteins and other complex systems. PMID:17766371

Spectroscopic study of proflavine adsorption on the carbon nanotube surface.

PubMed

Buchelnikov, Anatoly S; Dovbeshko, Galina I; Voronin, Dmitry P; Trachevsky, Vladimir V; Kostjukov, Viktor V; Evstigneev, Maxim P

2014-01-01

Despite the fact that non-covalent interactions between various aromatic compounds and carbon nanotubes are being extensively investigated now, there is still a lack of understanding about the nature of such interactions. The present paper sheds light on one of the possible mechanisms of interaction between the typical aromatic dye proflavine and the carbon nanotube surface, namely, π-stacking between aromatic rings of these compounds. To investigate such a complexation, a qualitative analysis was performed by means of ultraviolet visible, infrared, and nuclear magnetic resonance spectroscopy. The data obtained suggest that π-stacking brings the major contribution to the stabilization of the complex between proflavine and the carbon nanotube.

Ultrastable cellulosome-adhesion complex tightens under load

PubMed Central

Schoeler, Constantin; Malinowska, Klara H.; Bernardi, Rafael C.; Milles, Lukas F.; Jobst, Markus A.; Durner, Ellis; Ott, Wolfgang; Fried, Daniel B.; Bayer, Edward A.; Schulten, Klaus; Gaub, Hermann E.; Nash, Michael A.

2014-01-01

Challenging environments have guided nature in the development of ultrastable protein complexes. Specialized bacteria produce discrete multi-component protein networks called cellulosomes to effectively digest lignocellulosic biomass. While network assembly is enabled by protein interactions with commonplace affinities, we show that certain cellulosomal ligand–receptor interactions exhibit extreme resistance to applied force. Here, we characterize the ligand–receptor complex responsible for substrate anchoring in the Ruminococcus flavefaciens cellulosome using single-molecule force spectroscopy and steered molecular dynamics simulations. The complex withstands forces of 600–750 pN, making it one of the strongest bimolecular interactions reported, equivalent to half the mechanical strength of a covalent bond. Our findings demonstrate force activation and inter-domain stabilization of the complex, and suggest that certain network components serve as mechanical effectors for maintaining network integrity. This detailed understanding of cellulosomal network components may help in the development of biocatalysts for production of fuels and chemicals from renewable plant-derived biomass. PMID:25482395

A thorough experimental study of CH/π interactions in water: quantitative structure-stability relationships for carbohydrate/aromatic complexes.

PubMed

Jiménez-Moreno, Ester; Jiménez-Osés, Gonzalo; Gómez, Ana M; Santana, Andrés G; Corzana, Francisco; Bastida, Agatha; Jiménez-Barbero, Jesus; Asensio, Juan Luis

2015-11-13

CH/π interactions play a key role in a large variety of molecular recognition processes of biological relevance. However, their origins and structural determinants in water remain poorly understood. In order to improve our comprehension of these important interaction modes, we have performed a quantitative experimental analysis of a large data set comprising 117 chemically diverse carbohydrate/aromatic stacking complexes, prepared through a dynamic combinatorial approach recently developed by our group. The obtained free energies provide a detailed picture of the structure-stability relationships that govern the association process, opening the door to the rational design of improved carbohydrate-based ligands or carbohydrate receptors. Moreover, this experimental data set, supported by quantum mechanical calculations, has contributed to the understanding of the main driving forces that promote complex formation, underlining the key role played by coulombic and solvophobic forces on the stabilization of these complexes. This represents the most quantitative and extensive experimental study reported so far for CH/π complexes in water.

Experimental and Theoretical Study on Supramolecular Ionic Liquid (IL)-Asphaltene Complex Interactions and Their Effects on the Flow Properties of Heavy Crude Oils.

PubMed

Hernández-Bravo, R; Miranda, A D; Martínez-Magadán, J-M; Domínguez, J M

2018-04-19

A combined study for understanding the molecular interactions of asphaltenes with molecular species such as ionic liquids (ILs) comprised experimental measurements and computational numerical simulation calculations, using density-functional theory (DFT) with dispersion corrections, molecular dynamics (MD) calculations, and experimental rheological characterization of the heavy crude oils (HCOs), before and after doping with ILs, respectively. The main results show that ILs influence the asphaltenic dimer association by forming supramolecular complexes that modify the properties of crude oils such as viscosity and interfacial tension. The IL-cation and asphaltene-π ligand molecular interactions seem to dominate the interactions between ionic liquids and asphaltenes, where ILs' high aromaticity index induces a strong interaction with the aromatic hard core of asphaltenes.

Governability Framework for the Evaluation and Implementation of Complex Public Health Functions

ERIC Educational Resources Information Center

Varghese, Joe; Kutty, V. Raman

2012-01-01

Background: The dominant theoretical basis of our public health practice originates from a positivist or reductionist paradigm. It fails to take into account the complexity emerging out of public health's multiple influences originating from biological and social worlds. A deeper understanding of the interaction of elements that characterize the…

3D Reconstruction of Frozen Plant Tissue: a unique histological analysis to image post-freeze responses

USDA-ARS?s Scientific Manuscript database

Winter hardiness in plants is the result of a complex interaction between genes, the tissue where those genes are expressed and the environment. The light microscope is a valuable tool to understand this complexity which will ultimately help researchers improve the tolerance of plants to freezing st...

A Pilot Study to Teach Siblings to Support Children with Complex Communication Needs

ERIC Educational Resources Information Center

Douglas, Sarah N.; Kammes, Rebecca; Nordquist, Erica; D'Agostino, Sophia

2018-01-01

Siblings play an important role in the lives of children with disabilities, especially those with complex communication needs (CCN). However, children with CCN require support to learn social and communication skills. Like other communication partners, typically developing (TD) siblings may struggle to understand how to best interact with a child…

Hydrologic processes influencing meadow ecosystems [chapter 4

Treesearch

Mark L. Lord; David G. Jewett; Jerry R. Miller; Dru Germanoski; Jeanne C. Chambers

2011-01-01

The hydrologic regime exerts primary control on riparian meadow complexes and is strongly influenced by past and present geomorphic processes; biotic processes; and, in some cases, anthropogenic activities. Thus, it is essential to understand not only the hydrologic processes that operate within meadow complexes but also the interactions of meadow hydrology with other...

An integrated view of complex landscapes: a big data-model integration approach to trans-disciplinary science

USDA-ARS?s Scientific Manuscript database

The Earth is a complex system comprised of many interacting spatial and temporal scales. Understanding, predicting, and managing for these dynamics requires a trans-disciplinary integrated approach. Although there have been calls for this integration, a general approach is needed. We developed a Tra...

Chaordic Systems Thinking: Some Suggestions for a Complexity Framework to Inform a Learning Organization

ERIC Educational Resources Information Center

van Eijnatten, Frans M.

2004-01-01

This contribution suggests a conceptual framework for using complexity to understand human interactions in learning organizations. The particular lens adopted for this purpose is that of the Chaos perspective. The following general concepts are described: discontinuous growth, attractors: their basins and landscapes, the chaordic properties of…

Insight into genome variability in the Fusarium Incarnatum-equiseti species complex through comparative analysis of secondary metabolic biosynthetic gene clusters

USDA-ARS?s Scientific Manuscript database

The genus Fusarium comprises 22 species complexes that together include approximately 300 phylogenetically distinct species. A major focus in Fusarium literature is to understand the genetic basis of niche specialization, secondary metabolites (SM) production, and host interactions in closely relate...

Protein-protein interaction networks (PPI) and complex diseases

PubMed Central

Safari-Alighiarloo, Nahid; Taghizadeh, Mohammad; Rezaei-Tavirani, Mostafa; Goliaei, Bahram

2014-01-01

The physical interaction of proteins which lead to compiling them into large densely connected networks is a noticeable subject to investigation. Protein interaction networks are useful because of making basic scientific abstraction and improving biological and biomedical applications. Based on principle roles of proteins in biological function, their interactions determine molecular and cellular mechanisms, which control healthy and diseased states in organisms. Therefore, such networks facilitate the understanding of pathogenic (and physiologic) mechanisms that trigger the onset and progression of diseases. Consequently, this knowledge can be translated into effective diagnostic and therapeutic strategies. Furthermore, the results of several studies have proved that the structure and dynamics of protein networks are disturbed in complex diseases such as cancer and autoimmune disorders. Based on such relationship, a novel paradigm is suggested in order to confirm that the protein interaction networks can be the target of therapy for treatment of complex multi-genic diseases rather than individual molecules with disrespect the network. PMID:25436094

Understanding the nanoparticle-protein corona complexes using computational and experimental methods.

PubMed

Kharazian, B; Hadipour, N L; Ejtehadi, M R

2016-06-01

Nanoparticles (NP) have capability to adsorb proteins from biological fluids and form protein layer, which is called protein corona. As the cell sees corona coated NPs, the protein corona can dictate biological response to NPs. The composition of protein corona is varied by physicochemical properties of NPs including size, shape, surface chemistry. Processing of protein adsorption is dynamic phenomena; to that end, a protein may desorb or leave a surface vacancy that is rapidly filled by another protein and cause changes in the corona composition mainly by the Vroman effect. In this review, we discuss the interaction between NP and proteins and the available techniques for identification of NP-bound proteins. Also we review current developed computational methods for understanding the NP-protein complex interactions. Copyright © 2016. Published by Elsevier Ltd.

A theoretical probe on the non-covalent interactions of sulfadoxine drug with pi-acceptors

NASA Astrophysics Data System (ADS)

Sandhiya, L.; Senthilkumar, K.

2014-09-01

A detailed analysis of the interaction between an antimalarial drug sulfadoxine and four pi-acceptors, tetrachloro-catechol, picric acid, chloranil, and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone is presented in this study. The interaction of the amine, amide, methoxy, Csbnd H groups and π electron density of the drug molecule with the acceptors are studied using DFT method at M06-2X level of theory with 6-31G(d,p) basis set. The interaction energy of the complexes is calculated using M06-2X, M06-HF, B3LYP-D and MP2 methods with 6-31G(d,p) basis set. The role of weak interactions on the formation and stability of the complexes is discussed in detail. The two aromatic platforms of sulfadoxine play a major role in determining the stability of the complexes. The electron density difference maps have been plotted for the most stable drug interacting complexes to understand the changes in electron density delocalization upon the complex formation. The nature of the non-covalent interaction has been addressed from NCI plot. The infrared spectra calculated at M06-2X/6-31G(d,p) level of theory is used to characterize the most stable complexes. The SDOX-pi acceptor complexation leads to characteristic changes in the NMR spectra. The 13C, 1H, 17O and 15N NMR chemical shifts have been calculated using GIAO method at M06-2X/6-311+G(d,p)//M06-2X/6-31G(d,p) level of theory. The results obtained from this study confirm the role of non-covalent interactions on the function of the sulfadoxine drug.

Approaches to understanding the impact of life-history features on plant-pathogen co-evolutionary dynamics

Treesearch

Jeremy J. Burdon; Peter H. Thrall; Adnane Nemri

2012-01-01

Natural plant-pathogen associations are complex interactions in which the interplay of environment, host, and pathogen factors results in spatially heterogeneous ecological and epidemiological dynamics. The evolutionary patterns that result from the interaction of these factors are still relatively poorly understood. Recently, integration of the appropriate spatial and...

Visualizing and Quantifying the Suppressive Effects of Glucocorticoids on the Tadpole Immune System in Vivo

ERIC Educational Resources Information Center

Schreiber, Alexander M.

2011-01-01

A challenging topic in undergraduate physiology courses is the complex interaction between the vertebrate endocrine system and the immune system. There are relatively few established and accessible laboratory exercises available to instructors to help their students gain a working understanding of these interactions. The present laboratory module…

Understanding the Role of Metal Ions in RNA Folding and Function: Lessons from RNase P, a Ribonucleoprotein Enzyme

NASA Astrophysics Data System (ADS)

Harris, Michael E.; Christian, Eric L.

There is a large and rapidly growing literature relating RNA function to metal ion identity and concentration; however, due to the complexity and large number of interactions it remains a significant experimental challenge to tie the interactions of individual ions to specific aspects of RNA function. Investigation of the ribonculeopro-tein enzyme RNase P function has assisted in defining characteristics of RNA—metal ion interactions and provided a useful model system for understanding RNA catalysis and ribonucleoprotein assembly. The goal of this chapter is to review progress in understanding the physical basis of functional metal ion interactions with P RNA and relate this progress to the development of our understanding of RNA metal ion interactions in general. The research results reviewed here encompass: (1) Determination of the contribution of divalent metal ion binding to specific aspects of enzyme function, (2) Identification of individual metal ion binding sites in P RNA and their contribution to function, and (3) The effect of protein binding on RNA—metal ion affinity.

Statistical Mechanics of Temporal and Interacting Networks

NASA Astrophysics Data System (ADS)

Zhao, Kun

In the last ten years important breakthroughs in the understanding of the topology of complexity have been made in the framework of network science. Indeed it has been found that many networks belong to the universality classes called small-world networks or scale-free networks. Moreover it was found that the complex architecture of real world networks strongly affects the critical phenomena defined on these structures. Nevertheless the main focus of the research has been the characterization of single and static networks. Recently, temporal networks and interacting networks have attracted large interest. Indeed many networks are interacting or formed by a multilayer structure. Example of these networks are found in social networks where an individual might be at the same time part of different social networks, in economic and financial networks, in physiology or in infrastructure systems. Moreover, many networks are temporal, i.e. the links appear and disappear on the fast time scale. Examples of these networks are social networks of contacts such as face-to-face interactions or mobile-phone communication, the time-dependent correlations in the brain activity and etc. Understanding the evolution of temporal and multilayer networks and characterizing critical phenomena in these systems is crucial if we want to describe, predict and control the dynamics of complex system. In this thesis, we investigate several statistical mechanics models of temporal and interacting networks, to shed light on the dynamics of this new generation of complex networks. First, we investigate a model of temporal social networks aimed at characterizing human social interactions such as face-to-face interactions and phone-call communication. Indeed thanks to the availability of data on these interactions, we are now in the position to compare the proposed model to the real data finding good agreement. Second, we investigate the entropy of temporal networks and growing networks , to provide a new framework to quantify the information encoded in these networks and to answer a fundamental problem in network science: how complex are temporal and growing networks. Finally, we consider two examples of critical phenomena in interacting networks. In particular, on one side we investigate the percolation of interacting networks by introducing antagonistic interactions. On the other side, we investigate a model of political election based on the percolation of antagonistic networks. The aim of this research is to show how antagonistic interactions change the physics of critical phenomena on interacting networks. We believe that the work presented in these thesis offers the possibility to appreciate the large variability of problems that can be addressed in the new framework of temporal and interacting networks.

Pedagogical Considerations for Effectively Teaching Qualitative Research to Students in an Online Environment

ERIC Educational Resources Information Center

Bender, Sara; Hill, Karlie

2016-01-01

Qualitative research aims to understand both individual meaning as well as complex systemic interactions as they apply to social problems or individual experiences. This method of research is both inductive and flexible, allowing for a holistic approach that facilitates a rich understanding of the content examined. Past research identifies a…

Understanding Teachers' Pedagogical Choice: A Sociological Framework Combining the Work of Bourdieu and Giddens

ERIC Educational Resources Information Center

Burridge, Peter

2014-01-01

Understanding teachers' pedagogical choice provides a new insight into the influences on student achievement. This paper presents a sociological framework developed from the work of Pierre Bourdieu and Anthony Giddens that identify the complex social interactions which surround teacher's work. The framework examines teachers' potential to act…

Biomechanical concepts applicable to minimally invasive fracture repair in small animals.

PubMed

Chao, Peini; Lewis, Daniel D; Kowaleski, Michael P; Pozzi, Antonio

2012-09-01

Understanding the basic biomechanical principles of surgical stabilization of fractures is essential for developing an appropriate preoperative plan as well as making prudent intraoperative decisions. This article aims to provide basic biomechanical knowledge essential to the understanding of the complex interaction between the mechanics and biology of fracture healing. The type of healing and the outcome can be influenced by several mechanical factors, which depend on the interaction between bone and implant. The surgeon should understand the mechanical principles of fracture fixation and be able to choose the best type of fixation for each specific fracture. Copyright © 2012 Elsevier Inc. All rights reserved.

A novel approach to simulate gene-environment interactions in complex diseases.

PubMed

Amato, Roberto; Pinelli, Michele; D'Andrea, Daniel; Miele, Gennaro; Nicodemi, Mario; Raiconi, Giancarlo; Cocozza, Sergio

2010-01-05

Complex diseases are multifactorial traits caused by both genetic and environmental factors. They represent the major part of human diseases and include those with largest prevalence and mortality (cancer, heart disease, obesity, etc.). Despite a large amount of information that has been collected about both genetic and environmental risk factors, there are few examples of studies on their interactions in epidemiological literature. One reason can be the incomplete knowledge of the power of statistical methods designed to search for risk factors and their interactions in these data sets. An improvement in this direction would lead to a better understanding and description of gene-environment interactions. To this aim, a possible strategy is to challenge the different statistical methods against data sets where the underlying phenomenon is completely known and fully controllable, for example simulated ones. We present a mathematical approach that models gene-environment interactions. By this method it is possible to generate simulated populations having gene-environment interactions of any form, involving any number of genetic and environmental factors and also allowing non-linear interactions as epistasis. In particular, we implemented a simple version of this model in a Gene-Environment iNteraction Simulator (GENS), a tool designed to simulate case-control data sets where a one gene-one environment interaction influences the disease risk. The main aim has been to allow the input of population characteristics by using standard epidemiological measures and to implement constraints to make the simulator behaviour biologically meaningful. By the multi-logistic model implemented in GENS it is possible to simulate case-control samples of complex disease where gene-environment interactions influence the disease risk. The user has full control of the main characteristics of the simulated population and a Monte Carlo process allows random variability. A knowledge-based approach reduces the complexity of the mathematical model by using reasonable biological constraints and makes the simulation more understandable in biological terms. Simulated data sets can be used for the assessment of novel statistical methods or for the evaluation of the statistical power when designing a study.

Understanding the complexity of redesigning care around the clinical microsystem.

PubMed

Barach, P; Johnson, J K

2006-12-01

The microsystem is an organizing design construct in which social systems cut across traditional discipline boundaries. Because of its interdisciplinary focus, the clinical microsystem provides a conceptual and practical framework for simplifying complex organizations that deliver care. It also provides an important opportunity for organizational learning. Process mapping and microworld simulation may be especially useful for redesigning care around the microsystem concept. Process mapping, in which the core processes of the microsystem are delineated and assessed from the perspective of how the individual interacts with the system, is an important element of the continuous learning cycle of the microsystem and the healthcare organization. Microworld simulations are interactive computer based models that can be used as an experimental platform to test basic questions about decision making misperceptions, cause-effect inferences, and learning within the clinical microsystem. Together these tools offer the user and organization the ability to understand the complexity of healthcare systems and to facilitate the redesign of optimal outcomes.

Computer modeling and simulation of human movement. Applications in sport and rehabilitation.

PubMed

Neptune, R R

2000-05-01

Computer modeling and simulation of human movement plays an increasingly important role in sport and rehabilitation, with applications ranging from sport equipment design to understanding pathologic gait. The complex dynamic interactions within the musculoskeletal and neuromuscular systems make analyzing human movement with existing experimental techniques difficult but computer modeling and simulation allows for the identification of these complex interactions and causal relationships between input and output variables. This article provides an overview of computer modeling and simulation and presents an example application in the field of rehabilitation.

The structure of XIAP BIR2: understanding the selectivity of the BIR domains

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

Lukacs, Christine, E-mail: cmlukacs230@gmail.com; Belunis, Charles; Crowther, Robert

2013-09-01

The high-resolution crystal structures of apo and peptide-bound XIAP BIR2 are presented and compared with BIR3 structures to understand their selectivity. This crystal system can be used to determine the structures of BIR2–inhibitor complexes. XIAP, a member of the inhibitor of apoptosis family of proteins, is a critical regulator of apoptosis. Inhibition of the BIR domain–caspase interaction is a promising approach towards treating cancer. Previous work has been directed towards inhibiting the BIR3–caspase-9 interaction, which blocks the intrinsic apoptotic pathway; selectively inhibiting the BIR2–caspase-3 interaction would also block the extrinsic pathway. The BIR2 domain of XIAP has successfully been crystallized;more » peptides and small-molecule inhibitors can be soaked into these crystals, which diffract to high resolution. Here, the BIR2 apo crystal structure and the structures of five BIR2–tetrapeptide complexes are described. The structural flexibility observed on comparing these structures, along with a comparison with XIAP BIR3, affords an understanding of the structural elements that drive selectivity between BIR2 and BIR3 and which can be used to design BIR2-selective inhibitors.« less

Rigid-Docking Approaches to Explore Protein-Protein Interaction Space.

PubMed

Matsuzaki, Yuri; Uchikoga, Nobuyuki; Ohue, Masahito; Akiyama, Yutaka

Protein-protein interactions play core roles in living cells, especially in the regulatory systems. As information on proteins has rapidly accumulated on publicly available databases, much effort has been made to obtain a better picture of protein-protein interaction networks using protein tertiary structure data. Predicting relevant interacting partners from their tertiary structure is a challenging task and computer science methods have the potential to assist with this. Protein-protein rigid docking has been utilized by several projects, docking-based approaches having the advantages that they can suggest binding poses of predicted binding partners which would help in understanding the interaction mechanisms and that comparing docking results of both non-binders and binders can lead to understanding the specificity of protein-protein interactions from structural viewpoints. In this review we focus on explaining current computational prediction methods to predict pairwise direct protein-protein interactions that form protein complexes.

Thermodynamic characterization of the multivalent interactions underlying rapid and selective translocation through the nuclear pore complex

PubMed Central

Hayama, Ryo; Sparks, Samuel; Hecht, Lee M.; Dutta, Kaushik; Karp, Jerome M.; Cabana, Christina M.; Rout, Michael P.; Cowburn, David

2018-01-01

Intrinsically disordered proteins (IDPs) play important roles in many biological systems. Given the vast conformational space that IDPs can explore, the thermodynamics of the interactions with their partners is closely linked to their biological functions. Intrinsically disordered regions of Phe–Gly nucleoporins (FG Nups) that contain multiple phenylalanine–glycine repeats are of particular interest, as their interactions with transport factors (TFs) underlie the paradoxically rapid yet also highly selective transport of macromolecules mediated by the nuclear pore complex. Here, we used NMR and isothermal titration calorimetry to thermodynamically characterize these multivalent interactions. These analyses revealed that a combination of low per-FG motif affinity and the enthalpy–entropy balance prevents high-avidity interaction between FG Nups and TFs, whereas the large number of FG motifs promotes frequent FG–TF contacts, resulting in enhanced selectivity. Our thermodynamic model underlines the importance of functional disorder of FG Nups. It helps explain the rapid and selective translocation of TFs through the nuclear pore complex and further expands our understanding of the mechanisms of “fuzzy” interactions involving IDPs. PMID:29374059

Mapping Proteome-Wide Interactions of Reactive Chemicals Using Chemoproteomic Platforms

PubMed Central

Counihan, Jessica L.; Ford, Breanna; Nomura, Daniel K.

2015-01-01

A large number of pharmaceuticals, endogenous metabolites, and environmental chemicals act through covalent mechanisms with protein targets. Yet, their specific interactions with the proteome still remain poorly defined for most of these reactive chemicals. Deciphering direct protein targets of reactive small-molecules is critical in understanding their biological action, off-target effects, potential toxicological liabilities, and development of safer and more selective agents. Chemoproteomic technologies have arisen as a powerful strategy that enable the assessment of proteome-wide interactions of these irreversible agents directly in complex biological systems. We review here several chemoproteomic strategies that have facilitated our understanding of specific protein interactions of irreversibly-acting pharmaceuticals, endogenous metabolites, and environmental electrophiles to reveal novel pharmacological, biological, and toxicological mechanisms. PMID:26647369

Using machine learning tools to model complex toxic interactions with limited sampling regimes.

PubMed

Bertin, Matthew J; Moeller, Peter; Guillette, Louis J; Chapman, Robert W

2013-03-19

A major impediment to understanding the impact of environmental stress, including toxins and other pollutants, on organisms, is that organisms are rarely challenged by one or a few stressors in natural systems. Thus, linking laboratory experiments that are limited by practical considerations to a few stressors and a few levels of these stressors to real world conditions is constrained. In addition, while the existence of complex interactions among stressors can be identified by current statistical methods, these methods do not provide a means to construct mathematical models of these interactions. In this paper, we offer a two-step process by which complex interactions of stressors on biological systems can be modeled in an experimental design that is within the limits of practicality. We begin with the notion that environment conditions circumscribe an n-dimensional hyperspace within which biological processes or end points are embedded. We then randomly sample this hyperspace to establish experimental conditions that span the range of the relevant parameters and conduct the experiment(s) based upon these selected conditions. Models of the complex interactions of the parameters are then extracted using machine learning tools, specifically artificial neural networks. This approach can rapidly generate highly accurate models of biological responses to complex interactions among environmentally relevant toxins, identify critical subspaces where nonlinear responses exist, and provide an expedient means of designing traditional experiments to test the impact of complex mixtures on biological responses. Further, this can be accomplished with an astonishingly small sample size.

Linear Elastic Waves - Series: Cambridge Texts in Applied Mathematics (No. 26)

NASA Astrophysics Data System (ADS)

Harris, John G.

2001-10-01

Wave propagation and scattering are among the most fundamental processes that we use to comprehend the world around us. While these processes are often very complex, one way to begin to understand them is to study wave propagation in the linear approximation. This is a book describing such propagation using, as a context, the equations of elasticity. Two unifying themes are used. The first is that an understanding of plane wave interactions is fundamental to understanding more complex wave interactions. The second is that waves are best understood in an asymptotic approximation where they are free of the complications of their excitation and are governed primarily by their propagation environments. The topics covered include reflection, refraction, the propagation of interfacial waves, integral representations, radiation and diffraction, and propagation in closed and open waveguides. Linear Elastic Waves is an advanced level textbook directed at applied mathematicians, seismologists, and engineers. Aimed at beginning graduate students Includes examples and exercises Has application in a wide range of disciplines

Acetonitrile-water hydrogen-bonded interaction: Matrix-isolation infrared and ab initio computation

NASA Astrophysics Data System (ADS)

Gopi, R.; Ramanathan, N.; Sundararajan, K.

2015-08-01

The 1:1 hydrogen-bonded complex of acetonitrile (CH3CN) and water (H2O) was trapped in Ar and N2 matrices and studied using infrared technique. Ab initio computations showed two types of complexes formed between CH3CN and H2O, a linear complex A with a Ctbnd N⋯H interaction between nitrogen of CH3CN and hydrogen of H2O and a cyclic complex B, in which the interactions are between the hydrogen of CH3CN with oxygen of H2O and hydrogen of H2O with π cloud of sbnd Ctbnd N of CH3CN. Vibrational wavenumber calculations revealed that both the complexes A and B were minima on the potential energy surface. Interaction energies computed at B3LYP/6-311++G(d,p) showed that linear complex A is more stable than cyclic complex B. Computations identified a blue shift of ∼11.5 cm-1 and a red shift of ∼6.5 cm-1 in the CN stretching mode for the complexes A and B, respectively. Experimentally, we observed a blue shift of ∼15.0 and ∼8.3 cm-1 in N2 and Ar matrices, respectively, in the CN stretching mode of CH3CN, which supports the formation of complex A. The Onsager Self Consistent Reaction Field (SCRF) model was used to explain the influence of matrices on the complexes A and B. To understand the nature of the interactions, Atoms in Molecules (AIM) and Natural Bond Orbital (NBO) analyses were carried out for the complexes A and B.

Time-Series Analysis of Embodied Interaction: Movement Variability and Complexity Matching As Dyadic Properties

PubMed Central

Zapata-Fonseca, Leonardo; Dotov, Dobromir; Fossion, Ruben; Froese, Tom

2016-01-01

There is a growing consensus that a fuller understanding of social cognition depends on more systematic studies of real-time social interaction. Such studies require methods that can deal with the complex dynamics taking place at multiple interdependent temporal and spatial scales, spanning sub-personal, personal, and dyadic levels of analysis. We demonstrate the value of adopting an extended multi-scale approach by re-analyzing movement time-series generated in a study of embodied dyadic interaction in a minimal virtual reality environment (a perceptual crossing experiment). Reduced movement variability revealed an interdependence between social awareness and social coordination that cannot be accounted for by either subjective or objective factors alone: it picks out interactions in which subjective and objective conditions are convergent (i.e., elevated coordination is perceived as clearly social, and impaired coordination is perceived as socially ambiguous). This finding is consistent with the claim that interpersonal interaction can be partially constitutive of direct social perception. Clustering statistics (Allan Factor) of salient events revealed fractal scaling. Complexity matching defined as the similarity between these scaling laws was significantly more pronounced in pairs of participants as compared to surrogate dyads. This further highlights the multi-scale and distributed character of social interaction and extends previous complexity matching results from dyadic conversation to non-verbal social interaction dynamics. Trials with successful joint interaction were also associated with an increase in local coordination. Consequently, a local coordination pattern emerges on the background of complex dyadic interactions in the PCE task and makes joint successful performance possible. PMID:28018274

The problem of ecological scaling in spatially complex, nonequilibrium ecological systems [chapter 3

Treesearch

Samuel A. Cushman; Jeremy Littell; Kevin McGarigal

2010-01-01

In the previous chapter we reviewed the challenges posed by spatial complexity and temporal disequilibrium to efforts to understand and predict the structure and dynamics of ecological systems. The central theme was that spatial variability in the environment and population processes fundamentally alters the interactions between species and their environments, largely...

A practical approach for comparing management strategies in complex forest ecosystems using meta-modelling toolkits

Treesearch

Andrew Fall; B. Sturtevant; M.-J. Fortin; M. Papaik; F. Doyon; D. Morgan; K. Berninger; C. Messier

2010-01-01

The complexity and multi-scaled nature of forests poses significant challenges to understanding and management. Models can provide useful insights into process and their interactions, and implications of alternative management options. Most models, particularly scientific models, focus on a relatively small set of processes and are designed to operate within a...

Nanoindentation methods for wood-adhesive bond lines

Treesearch

Joseph E. Jakes; Donald S. Stone; Charles R. Frihart

2008-01-01

As an adherend, wood is structurally, chemically, and mechanically more complex than metals or plastics, and the largest source of this complexity is wood’s chemical and mechanical inhomogeneities. Understanding and predicting the performance of adhesively bonded wood requires knowledge of the interactions occurring at length scales ranging from the macro down to the...

Using Representational Tools to Learn about Complex Systems: A Tale of Two Classrooms

ERIC Educational Resources Information Center

Hmelo-Silver, Cindy E.; Liu, Lei; Gray, Steven; Jordan, Rebecca

2015-01-01

Orchestrating inquiry-based science learning in the classroom is a complex undertaking. It requires fitting the culture of the classroom with the teacher's teaching and inquiry practices. To understand the interactions between these variables in relation to student learning, we conducted an investigation in two different classroom settings to…

Energy Landscape of All-Atom Protein-Protein Interactions Revealed by Multiscale Enhanced Sampling

PubMed Central

Moritsugu, Kei; Terada, Tohru; Kidera, Akinori

2014-01-01

Protein-protein interactions are regulated by a subtle balance of complicated atomic interactions and solvation at the interface. To understand such an elusive phenomenon, it is necessary to thoroughly survey the large configurational space from the stable complex structure to the dissociated states using the all-atom model in explicit solvent and to delineate the energy landscape of protein-protein interactions. In this study, we carried out a multiscale enhanced sampling (MSES) simulation of the formation of a barnase-barstar complex, which is a protein complex characterized by an extraordinary tight and fast binding, to determine the energy landscape of atomistic protein-protein interactions. The MSES adopts a multicopy and multiscale scheme to enable for the enhanced sampling of the all-atom model of large proteins including explicit solvent. During the 100-ns MSES simulation of the barnase-barstar system, we observed the association-dissociation processes of the atomistic protein complex in solution several times, which contained not only the native complex structure but also fully non-native configurations. The sampled distributions suggest that a large variety of non-native states went downhill to the stable complex structure, like a fast folding on a funnel-like potential. This funnel landscape is attributed to dominant configurations in the early stage of the association process characterized by near-native orientations, which will accelerate the native inter-molecular interactions. These configurations are guided mostly by the shape complementarity between barnase and barstar, and lead to the fast formation of the final complex structure along the downhill energy landscape. PMID:25340714

Determining the Composition and Stability of Protein Complexes Using an Integrated Label-Free and Stable Isotope Labeling Strategy

PubMed Central

Greco, Todd M.; Guise, Amanda J.; Cristea, Ileana M.

2016-01-01

In biological systems, proteins catalyze the fundamental reactions that underlie all cellular functions, including metabolic processes and cell survival and death pathways. These biochemical reactions are rarely accomplished alone. Rather, they involve a concerted effect from many proteins that may operate in a directed signaling pathway and/or may physically associate in a complex to achieve a specific enzymatic activity. Therefore, defining the composition and regulation of protein complexes is critical for understanding cellular functions. In this chapter, we describe an approach that uses quantitative mass spectrometry (MS) to assess the specificity and the relative stability of protein interactions. Isolation of protein complexes from mammalian cells is performed by rapid immunoaffinity purification, and followed by in-solution digestion and high-resolution mass spectrometry analysis. We employ complementary quantitative MS workflows to assess the specificity of protein interactions using label-free MS and statistical analysis, and the relative stability of the interactions using a metabolic labeling technique. For each candidate protein interaction, scores from the two workflows can be correlated to minimize nonspecific background and profile protein complex composition and relative stability. PMID:26867737

The solvation structure of alprazolam.

PubMed

Sridhar, Akshay; Johnston, Andrew J; Varathan, Luxmmi; McLain, Sylvia E; Biggin, Philip C

2016-08-10

Alprazolam is a benzodiazepine that is commonly prescribed for the treatment of anxiety and other related disorders. Like other benzodiazepines, it is thought to exert its effect through interaction with GABAA receptors. However, it has also been described as a potent and selective protein interaction inhibitor of bromodomain and extra-terminal (BET) proteins. Indeed, the only crystal structure of alprazolam bound to a protein is a complex between alprazolam and the BRD4 bromodomain. The structure shows that the complex also involves many water interactions that mediate contacts between the drug and the protein, a scenario that exists in many drug-protein complexes. How such waters relate to solvation patterns of small molecules may improve our understanding of what dictates their appearance or absence in bridging positions within complexes and thus will be important in terms of future rational drug-design. Here, we use neutron diffraction in conjunction with molecular dynamics simulations to provide a detailed analysis of how water molecules interact with alprazolam in methanol/water mixtures. The agreement between the neutron diffraction and the molecular dynamics is extremely good. We discuss the results in the context of drug design.

Interactions of cisplatin with non-DNA targets and their influence on anticancer activity and drug toxicity: the complex world of the platinum complex.

PubMed

Mezencev, Roman

2015-01-01

Since the discovery of its anticancer activity in 1970s, cisplatin and its analogs have become widely used in clinical practice, being administered to 40-80% of patients undergoing chemotherapy for solid tumors. The fascinating story of this drug continues to evolve presently, which includes advances in our understanding of complexity of molecular mechanisms involved in its anticancer activity and drug toxicity. While genomic DNA has been generally recognized as the most critical pharmacological target of cisplatin, the results reported across multiple disciplines suggest that other targets and molecular interactions are likely involved in the anticancer mode of action, drug toxicity and resistance of cancer cells to this remarkable anticancer drug. This article reviews interactions of cisplatin with non-DNA targets, including RNAs, proteins, phospholipids and carbohydrates in the context of its pharmacological activity and drug toxicity. Some of these non-DNA targets and associated mechanisms likely act in a highly concerted manner towards the biological outcome in cisplatin-treated tumors; therefore, the understanding of complexity of cisplatin interactome may open new avenues for modulation of its clinical efficacy or for designing more efficient platinum-based anticancer drugs to reproduce the success of cisplatin in the treatment of highly curable testicular germ cell tumors in its therapeutic applications to other cancers.

Protein-protein interaction predictions using text mining methods.

PubMed

Papanikolaou, Nikolas; Pavlopoulos, Georgios A; Theodosiou, Theodosios; Iliopoulos, Ioannis

2015-03-01

It is beyond any doubt that proteins and their interactions play an essential role in most complex biological processes. The understanding of their function individually, but also in the form of protein complexes is of a great importance. Nowadays, despite the plethora of various high-throughput experimental approaches for detecting protein-protein interactions, many computational methods aiming to predict new interactions have appeared and gained interest. In this review, we focus on text-mining based computational methodologies, aiming to extract information for proteins and their interactions from public repositories such as literature and various biological databases. We discuss their strengths, their weaknesses and how they complement existing experimental techniques by simultaneously commenting on the biological databases which hold such information and the benchmark datasets that can be used for evaluating new tools. Copyright © 2014 Elsevier Inc. All rights reserved.

CLIMLAB: a Python-based software toolkit for interactive, process-oriented climate modeling

NASA Astrophysics Data System (ADS)

Rose, B. E. J.

2015-12-01

Global climate is a complex emergent property of the rich interactions between simpler components of the climate system. We build scientific understanding of this system by breaking it down into component process models (e.g. radiation, large-scale dynamics, boundary layer turbulence), understanding each components, and putting them back together. Hands-on experience and freedom to tinker with climate models (whether simple or complex) is invaluable for building physical understanding. CLIMLAB is an open-ended software engine for interactive, process-oriented climate modeling. With CLIMLAB you can interactively mix and match model components, or combine simpler process models together into a more comprehensive model. It was created primarily to support classroom activities, using hands-on modeling to teach fundamentals of climate science at both undergraduate and graduate levels. CLIMLAB is written in Python and ties in with the rich ecosystem of open-source scientific Python tools for numerics and graphics. The IPython notebook format provides an elegant medium for distributing interactive example code. I will give an overview of the current capabilities of CLIMLAB, the curriculum we have developed thus far, and plans for the future. Using CLIMLAB requires some basic Python coding skills. We consider this an educational asset, as we are targeting upper-level undergraduates and Python is an increasingly important language in STEM fields. However CLIMLAB is well suited to be deployed as a computational back-end for a graphical gaming environment based on earth-system modeling.

Landscape community genomics: understanding eco-evolutionary processes in complex environments

USGS Publications Warehouse

Hand, Brian K.; Lowe, Winsor H.; Kovach, Ryan P.; Muhlfeld, Clint C.; Luikart, Gordon

2015-01-01

Extrinsic factors influencing evolutionary processes are often categorically lumped into interactions that are environmentally (e.g., climate, landscape) or community-driven, with little consideration of the overlap or influence of one on the other. However, genomic variation is strongly influenced by complex and dynamic interactions between environmental and community effects. Failure to consider both effects on evolutionary dynamics simultaneously can lead to incomplete, spurious, or erroneous conclusions about the mechanisms driving genomic variation. We highlight the need for a landscape community genomics (LCG) framework to help to motivate and challenge scientists in diverse fields to consider a more holistic, interdisciplinary perspective on the genomic evolution of multi-species communities in complex environments.

Peer Interaction and Learning in Multilingual Settings from a Sociocultural Perspective: Theoretical Insights

ERIC Educational Resources Information Center

Kibler, Amanda

2017-01-01

Reflecting on contributions to this special issue along with my own research, I suggest ways in which sociocultural understandings of peer interactions in multilingual contexts are and should be evolving to encompass the increasingly complex settings that research has come to document. I argue that in order to realize the potential of research in…

Spectroscopic exploration of interaction between PEG-functionalized Ag2S nanoparticles with bovine serum albumin

NASA Astrophysics Data System (ADS)

Prasanth, S.; RitheshRaj, D.; Vineeshkumar, T. V.; Sudarsanakumar, C.

2018-05-01

The introduction of nanoparticles into biological fluids often leads to the formation of biocorona over the surface of nanoparticles. For the effective use of nanoparticles in biological applications it is very essential to understand their interactions with proteins. Herein, we investigated the interactions of Poly ethylene glycol capped Ag2S nanoparticles with Bovine Serum Albumin by spectroscopic techniques. By the addition of Ag2S nanoparticles, a ground state complex is formed. The CD spectroscopy reveals that the secondary structure of BSA is altered by complexation with PEG-Ag2S nanoparticles, while the overall tertiary structure remains closer to that of native BSA.

Bacterial biodiversity-ecosystem functioning relations are modified by environmental complexity.

PubMed

Langenheder, Silke; Bulling, Mark T; Solan, Martin; Prosser, James I

2010-05-26

With the recognition that environmental change resulting from anthropogenic activities is causing a global decline in biodiversity, much attention has been devoted to understanding how changes in biodiversity may alter levels of ecosystem functioning. Although environmental complexity has long been recognised as a major driving force in evolutionary processes, it has only recently been incorporated into biodiversity-ecosystem functioning investigations. Environmental complexity is expected to strengthen the positive effect of species richness on ecosystem functioning, mainly because it leads to stronger complementarity effects, such as resource partitioning and facilitative interactions among species when the number of available resource increases. Here we implemented an experiment to test the combined effect of species richness and environmental complexity, more specifically, resource richness on ecosystem functioning over time. We show, using all possible combinations of species within a bacterial community consisting of six species, and all possible combinations of three substrates, that diversity-functioning (metabolic activity) relationships change over time from linear to saturated. This was probably caused by a combination of limited complementarity effects and negative interactions among competing species as the experiment progressed. Even though species richness and resource richness both enhanced ecosystem functioning, they did so independently from each other. Instead there were complex interactions between particular species and substrate combinations. Our study shows clearly that both species richness and environmental complexity increase ecosystem functioning. The finding that there was no direct interaction between these two factors, but that instead rather complex interactions between combinations of certain species and resources underlie positive biodiversity ecosystem functioning relationships, suggests that detailed knowledge of how individual species interact with complex natural environments will be required in order to make reliable predictions about how altered levels of biodiversity will most likely affect ecosystem functioning.

Bacterial Biodiversity-Ecosystem Functioning Relations Are Modified by Environmental Complexity

PubMed Central

Langenheder, Silke; Bulling, Mark T.; Solan, Martin; Prosser, James I.

2010-01-01

Background With the recognition that environmental change resulting from anthropogenic activities is causing a global decline in biodiversity, much attention has been devoted to understanding how changes in biodiversity may alter levels of ecosystem functioning. Although environmental complexity has long been recognised as a major driving force in evolutionary processes, it has only recently been incorporated into biodiversity-ecosystem functioning investigations. Environmental complexity is expected to strengthen the positive effect of species richness on ecosystem functioning, mainly because it leads to stronger complementarity effects, such as resource partitioning and facilitative interactions among species when the number of available resource increases. Methodology/Principal Findings Here we implemented an experiment to test the combined effect of species richness and environmental complexity, more specifically, resource richness on ecosystem functioning over time. We show, using all possible combinations of species within a bacterial community consisting of six species, and all possible combinations of three substrates, that diversity-functioning (metabolic activity) relationships change over time from linear to saturated. This was probably caused by a combination of limited complementarity effects and negative interactions among competing species as the experiment progressed. Even though species richness and resource richness both enhanced ecosystem functioning, they did so independently from each other. Instead there were complex interactions between particular species and substrate combinations. Conclusions/Significance Our study shows clearly that both species richness and environmental complexity increase ecosystem functioning. The finding that there was no direct interaction between these two factors, but that instead rather complex interactions between combinations of certain species and resources underlie positive biodiversity ecosystem functioning relationships, suggests that detailed knowledge of how individual species interact with complex natural environments will be required in order to make reliable predictions about how altered levels of biodiversity will most likely affect ecosystem functioning. PMID:20520808

Resolving protein interactions and organization downstream the T cell antigen receptor using single-molecule localization microscopy: a review

NASA Astrophysics Data System (ADS)

Sherman, Eilon

2016-06-01

Signal transduction is mediated by heterogeneous and dynamic protein complexes. Such complexes play a critical role in diverse cell functions, with the important example of T cell activation. Biochemical studies of signalling complexes and their imaging by diffraction limited microscopy have resulted in an intricate network of interactions downstream the T cell antigen receptor (TCR). However, in spite of their crucial roles in T cell activation, much remains to be learned about these signalling complexes, including their heterogeneous contents and size distribution, their complex arrangements in the PM, and the molecular requirements for their formation. Here, we review how recent advancements in single molecule localization microscopy have helped to shed new light on the organization of signalling complexes in single molecule detail in intact T cells. From these studies emerges a picture where cells extensively employ hierarchical and dynamic patterns of nano-scale organization to control the local concentration of interacting molecular species. These patterns are suggested to play a critical role in cell decision making. The combination of SMLM with more traditional techniques is expected to continue and critically contribute to our understanding of multimolecular protein complexes and their significance to cell function.

Interactions of platinum metals and their complexes in biological systems.

PubMed Central

LeRoy, A F

1975-01-01

Platinum-metal oxidation catalysts are to be introduced in exhaust systems of many 1975 model-year automobiles in the U.S. to meet Clean Air Act standards. Small quantities of finely divided catalyst have been found issuing from prototype systems; platinum and palladium compounds may be found also. Although platinum exhibits a remarkable resistance to oxidation and chemical attack, it reacts chemically under some conditions producing coordination complex compounds. Palladium reacts more readily than platinum. Some platinum-metal complexes interact with biological systems as bacteriostatic, bacteriocidal, viricidal, and immunosuppressive agents. Workers chronically exposed to platinum complexes often develop asthma-like respiratory distress and skin reactions called platinosis. Platinum complexes used alone and in combination therapy with other drugs have recently emerged as effective agents in cancer chemotherapy. Understanding toxic and favorable interactions of metal species with living organisms requires basic information on quantities and chemical characteristics of complexes at trace concentrations in biological materials. Some basic chemical kinetic and thermodynamic data are presented to characterize the chemical behavior of the complex cis-[Pt(NH3)2Cl2] used therapeutically. A brief discussion of platinum at manogram levels in biological tissue is discussed. PMID:50943

Proteomic analysis in non-denaturing condition of the secretome reveals the presence of multienzyme complexes in Penicillium purpurogenum.

PubMed

Gonzalez-Vogel, Alvaro; Eyzaguirre, Jaime; Oleas, Gabriela; Callegari, Eduardo; Navarrete, Mario

2011-01-01

Proteins secreted by filamentous fungi play key roles in different aspects of their biology. The fungus Penicillium purpurogenum, used as a model organism, is able to degrade hemicelluloses and pectins by secreting a variety of enzymes to the culture medium. This work shows that these enzymes interact with each other to form high molecular weight, catalytically active complexes. By using a proteomics approach, we were able to identify several protein complexes in the secretome of this fungus. The expression and assembly of these complexes depend on the carbon source used and display molecular masses ranging from 300 to 700 kDa. These complexes are composed of a variety of enzymes, including arabinofuranosidases, acetyl xylan esterases, feruloyl esterases, β-glucosidases and xylanases. The protein-protein interactions in these multienzyme complexes were confirmed by coimmunoprecipitation assays. One of the complexes was purified from sugar beet pulp cultures and the subunits identified by tandem mass spectrometry. A better understanding of the biological significance of these kinds of interactions will help in the comprehension of the degradation mechanisms used by fungi and may be of special interest to the biotechnology industry.

Exploring the application of an evolutionary educational complex systems framework to teaching and learning about issues in the science and technology classroom

NASA Astrophysics Data System (ADS)

Yoon, Susan Anne

Understanding the world through a complex systems lens has recently garnered a great deal of interest in many knowledge disciplines. In the educational arena, interactional studies, through their focus on understanding patterns of system behaviour including the dynamical processes and trajectories of learning, lend support for investigating how a complex systems approach can inform educational research. This study uses previously existing literature and tools for complex systems applications and seeks to extend this research base by exploring learning outcomes of a complex systems framework when applied to curriculum and instruction. It is argued that by applying the evolutionary dynamics of variation, interaction and selection, complexity may be harnessed to achieve growth in both the social and cognitive systems of the classroom. Furthermore, if the goal of education, i.e., the social system under investigation, is to teach for understanding, conceptual knowledge of the kind described in Popper's (1972; 1976) World 3, needs to evolve. Both the study of memetic processes and knowledge building pioneered by Bereiter (cf. Bereiter, 2002) draw on the World 3 notion of ideas existing as conceptual artifacts that can be investigated as products outside of the individual mind providing an educational lens from which to proceed. The curricular topic addressed is the development of an ethical understanding of the scientific and technological issues of genetic engineering. 11 grade 8 students are studied as they proceed through 40 hours of curricular instruction based on the complex systems evolutionary framework. Results demonstrate growth in both complex systems thinking and content knowledge of the topic of genetic engineering. Several memetic processes are hypothesized to have influenced how and why ideas change. Categorized by factors influencing either reflective or non-reflective selection, these processes appear to have exerted differential effects on students' abilities to think and act in complex ways at various points throughout the study. Finally, an analysis of winner and loser memes is offered that is intended to reveal information about the conceptual system---its strengths and deficiencies---that can help educators assess curricular goals and organize and construct additional educational activities.

Fort Collins Science Center Ecosystem Dynamics Branch

USGS Publications Warehouse

Wilson, Jim; Melcher, C.; Bowen, Z.

2009-01-01

Complex natural resource issues require understanding a web of interactions among ecosystem components that are (1) interdisciplinary, encompassing physical, chemical, and biological processes; (2) spatially complex, involving movements of animals, water, and airborne materials across a range of landscapes and jurisdictions; and (3) temporally complex, occurring over days, weeks, or years, sometimes involving response lags to alteration or exhibiting large natural variation. Scientists in the Ecosystem Dynamics Branch of the U.S. Geological Survey, Fort Collins Science Center, investigate a diversity of these complex natural resource questions at the landscape and systems levels. This Fact Sheet describes the work of the Ecosystems Dynamics Branch, which is focused on energy and land use, climate change and long-term integrated assessments, herbivore-ecosystem interactions, fire and post-fire restoration, and environmental flows and river restoration.

Synchronization in complex networks

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

Arenas, A.; Diaz-Guilera, A.; Moreno, Y.

Synchronization processes in populations of locally interacting elements are in the focus of intense research in physical, biological, chemical, technological and social systems. The many efforts devoted to understand synchronization phenomena in natural systems take now advantage of the recent theory of complex networks. In this review, we report the advances in the comprehension of synchronization phenomena when oscillating elements are constrained to interact in a complex network topology. We also overview the new emergent features coming out from the interplay between the structure and the function of the underlying pattern of connections. Extensive numerical work as well as analyticalmore » approaches to the problem are presented. Finally, we review several applications of synchronization in complex networks to different disciplines: biological systems and neuroscience, engineering and computer science, and economy and social sciences.« less

NOD1CARD Might Be Using Multiple Interfaces for RIP2-Mediated CARD-CARD Interaction: Insights from Molecular Dynamics Simulation

PubMed Central

Pradhan, Sukanta Kumar; De, Sachinandan

2017-01-01

The nucleotide-binding and oligomerization domain (NOD)-containing protein 1 (NOD1) plays the pivotal role in host-pathogen interface of innate immunity and triggers immune signalling pathways for the maturation and release of pro-inflammatory cytokines. Upon the recognition of iE-DAP, NOD1 self-oligomerizes in an ATP-dependent fashion and interacts with adaptor molecule receptor-interacting protein 2 (RIP2) for the propagation of innate immune signalling and initiation of pro-inflammatory immune responses. This interaction (mediated by NOD1 and RIP2) helps in transmitting the downstream signals for the activation of NF-κB signalling pathway, and has been arbitrated by respective caspase-recruitment domains (CARDs). The so-called CARD-CARD interaction still remained contradictory due to inconsistent results. Henceforth, to understand the mode and the nature of the interaction, structural bioinformatics approaches were employed. MD simulation of modelled 1:1 heterodimeric complexes revealed that the type-Ia interface of NOD1CARD and the type-Ib interface of RIP2CARD might be the suitable interfaces for the said interaction. Moreover, we perceived three dynamically stable heterotrimeric complexes with an NOD1:RIP2 ratio of 1:2 (two numbers) and 2:1. Out of which, in the first trimeric complex, a type-I NOD1-RIP2 heterodimer was found interacting with an RIP2CARD using their type-IIa and IIIa interfaces. However, in the second and third heterotrimer, we observed type-I homodimers of NOD1 and RIP2 CARDs were interacting individually with RIP2CARD and NOD1CARD (in type-II and type-III interface), respectively. Overall, this study provides structural and dynamic insights into the NOD1-RIP2 oligomer formation, which will be crucial in understanding the molecular basis of NOD1-mediated CARD-CARD interaction in higher and lower eukaryotes. PMID:28114344

In Touch with Molecules: Improving Student Learning with Innovative Molecular Models

ERIC Educational Resources Information Center

Davenport, Jodi; Silberglitt, Matt; Olson, Arthur

2013-01-01

How do viruses self-assemble? Why do DNA bases pair the way they do? What factors determine whether strands of proteins fold into sheets or helices? Why does handedness matter? A deep understanding of core issues in biology requires students to understand both complex spatial structures of molecules and the interactions involved in dynamic…

The Effects of Visualizations on Linguistically Diverse Students' Understanding of Energy and Matter in Life Science

ERIC Educational Resources Information Center

Ryoo, Kihyun; Bedell, Kristin

2017-01-01

Although extensive research has shown the educational value of different types of interactive visualizations on students' science learning in general, how such technologies can contribute to English learners' (ELs) understanding of complex scientific concepts has not been sufficiently explored to date. This mixed-methods study investigated how…

Simple processes drive unpredictable differences in estuarine fish assemblages: Baselines for understanding site-specific ecological and anthropogenic impacts

NASA Astrophysics Data System (ADS)

Sheaves, Marcus

2016-03-01

Predicting patterns of abundance and composition of biotic assemblages is essential to our understanding of key ecological processes, and our ability to monitor, evaluate and manage assemblages and ecosystems. Fish assemblages often vary from estuary to estuary in apparently unpredictable ways, making it challenging to develop a general understanding of the processes that determine assemblage composition. This makes it problematic to transfer understanding from one estuary situation to another and therefore difficult to assemble effective management plans or to assess the impacts of natural and anthropogenic disturbance. Although system-to-system variability is a common property of ecological systems, rather than being random it is the product of complex interactions of multiple causes and effects at a variety of spatial and temporal scales. I investigate the drivers of differences in estuary fish assemblages, to develop a simple model explaining the diversity and complexity of observed estuary-to-estuary differences, and explore its implications for management and conservation. The model attributes apparently unpredictable differences in fish assemblage composition from estuary to estuary to the interaction of species-specific, life history-specific and scale-specific processes. In explaining innate faunal differences among estuaries without the need to invoke complex ecological or anthropogenic drivers, the model provides a baseline against which the effects of additional natural and anthropogenic factors can be evaluated.

Joining Forces: Integrating Proteomics and Cross-linking with the Mass Spectrometry of Intact Complexes*

PubMed Central

Stengel, Florian; Aebersold, Ruedi; Robinson, Carol V.

2012-01-01

Protein assemblies are critical for cellular function and understanding their physical organization is the key aim of structural biology. However, applying conventional structural biology approaches is challenging for transient, dynamic, or polydisperse assemblies. There is therefore a growing demand for hybrid technologies that are able to complement classical structural biology methods and thereby broaden our arsenal for the study of these important complexes. Exciting new developments in the field of mass spectrometry and proteomics have added a new dimension to the study of protein-protein interactions and protein complex architecture. In this review, we focus on how complementary mass spectrometry-based techniques can greatly facilitate structural understanding of protein assemblies. PMID:22180098

The Evolution of Integrated Assessment and Emerging Challenges in the Assessment of Human and Natural System Interactions

NASA Astrophysics Data System (ADS)

Clarke, L.

2017-12-01

Integrated assessment (IA) modeling and research has a long history, spanning over 30 years since its inception and addressing a wide range of contemporary issues along the way. Over the last decade, IA modeling and research has emerged as one of the primary analytical methods for understanding the complex interactions between human and natural systems, from the interactions between energy, water, and land/food systems to the interplay between health, climate, and air pollution. IA modeling and research is particularly well-suited for the analysis of these interactions because it is a discipline that strives to integrate representations of multiple systems into consistent computational platforms or frameworks. In doing so, it explicitly confronts the many tradeoffs that are frequently necessary to manage complexity and computational cost while still representing the most important interactions and overall, coupled system behavior. This talk explores the history of IA modeling and research as a means to better understand its role in the assessment of contemporary issues at the confluence of human and natural systems. It traces the evolution of IA modeling and research from initial exploration of long-term emissions pathways, to the role of technology in the global evolution of the energy system, to the key linkages between land and energy systems and, more recently, the linkages with water, air pollution, and other key systems and issues. It discusses the advances in modeling that have emerged over this evolution and the biggest challenges that still present themselves as we strive to better understand the most important interactions between human and natural systems and the implications of these interactions for human welfare and decision making.

Influence of dissolved organic matter on the complexation of mercury under sulfidic conditions.

PubMed

Miller, Carrie L; Mason, Robert P; Gilmour, Cynthia C; Heyes, Andrew

2007-04-01

The complexation of Hg under sulfidic conditions influences its bioavailability for microbial methylation. Neutral dissolved Hg-sulfide complexes are readily available to Hg-methylating bacteria in culture, and thermodynamic models predict that inorganic Hg-sulfide complexes dominate dissolved Hg speciation under natural sulfidic conditions. However, these models have not been validated in the field. To examine the complexation of Hg in natural sulfidic waters, octanol/water partitioning methods were modified for use under environmentally relevant conditions, and a centrifuge ultrafiltration technique was developed. These techniques demonstrated much lower concentrations of dissolved Hg-sulfide complexes than predicted. Furthermore, the study revealed an interaction between Hg, dissolved organic matter (DOM), and sulfide that is not captured by current thermodynamic models. Whereas Hg forms strong complexes with DOM under oxic conditions, these complexes had not been expected to form in the presence of sulfide because of the stronger affinity of Hg for sulfide relative to its affinity for DOM. The observed interaction between Hg and DOM in the presence of sulfide likely involves the formation of a DOM-Hg-sulfide complex or results from the hydrophobic partitioning of neutral Hg-sulfide complexes into the higher-molecular-weight DOM. An understanding of the mechanism of this interaction and determination of complexation coefficients for the Hg-sulfide-DOM complex are needed to adequately assess how our new finding affects Hg bioavailability, sorption, and flux.

The spatiotemporal system dynamics of acquired resistance in an engineered microecology.

PubMed

Datla, Udaya Sree; Mather, William H; Chen, Sheng; Shoultz, Isaac W; Täuber, Uwe C; Jones, Caroline N; Butzin, Nicholas C

2017-11-22

Great strides have been made in the understanding of complex networks; however, our understanding of natural microecologies is limited. Modelling of complex natural ecological systems has allowed for new findings, but these models typically ignore the constant evolution of species. Due to the complexity of natural systems, unanticipated interactions may lead to erroneous conclusions concerning the role of specific molecular components. To address this, we use a synthetic system to understand the spatiotemporal dynamics of growth and to study acquired resistance in vivo. Our system differs from earlier synthetic systems in that it focuses on the evolution of a microecology from a killer-prey relationship to coexistence using two different non-motile Escherichia coli strains. Using empirical data, we developed the first ecological model emphasising the concept of the constant evolution of species, where the survival of the prey species is dependent on location (distance from the killer) or the evolution of resistance. Our simple model, when expanded to complex microecological association studies under varied spatial and nutrient backgrounds may help to understand the complex relationships between multiple species in intricate natural ecological networks. This type of microecological study has become increasingly important, especially with the emergence of antibiotic-resistant pathogens.

Emergent processes in cognitive-emotional interactions

PubMed Central

Pessoa, Luiz

2010-01-01

Emotion and cognition have been viewed as largely separate entities in the brain. Within this framework, significant progress has been made in understanding specific aspects of behavior. Research in the past two decades, however, has started to paint a different picture of brain organization, one in which network interactions are key to understanding complex behaviors. From both basic and clinical perspectives, the characterization of cognitive-emotional interactions constitutes a fundamental issue in the investigation of the mind and brain. This review will highlight the interactive and integrative potential that exists in the brain to bring together the cognitive and emotional domains. First, anatomical evidence will be provided, focusing on structures such as hypothalamus, basal forebrain, amygdala, cingulate cortex, orbitofrontal cortex, and insula. Data on functional interactions will then be discussed, followed by a discussion of a dual competition framework, which describes cognitive-emotional interactions in terms of perceptual and cognitive competition mechanisms. PMID:21319489

Climate change and the past, present, and future of biotic interactions.

PubMed

Blois, Jessica L; Zarnetske, Phoebe L; Fitzpatrick, Matthew C; Finnegan, Seth

2013-08-02

Biotic interactions drive key ecological and evolutionary processes and mediate ecosystem responses to climate change. The direction, frequency, and intensity of biotic interactions can in turn be altered by climate change. Understanding the complex interplay between climate and biotic interactions is thus essential for fully anticipating how ecosystems will respond to the fast rates of current warming, which are unprecedented since the end of the last glacial period. We highlight episodes of climate change that have disrupted ecosystems and trophic interactions over time scales ranging from years to millennia by changing species' relative abundances and geographic ranges, causing extinctions, and creating transient and novel communities dominated by generalist species and interactions. These patterns emerge repeatedly across disparate temporal and spatial scales, suggesting the possibility of similar underlying processes. Based on these findings, we identify knowledge gaps and fruitful areas for research that will further our understanding of the effects of climate change on ecosystems.

Rivers are social–ecological systems: Time to integrate human dimensions into riverscape ecology and management

USGS Publications Warehouse

Dunham, Jason B.; Angermeier, Paul L.; Crausbay, Shelley D.; Cravens, Amanda; Gosnell, Hannah; McEvoy, Jamie; Moritz, Max A.; Raheem, Nejem; Sanford, Todd

2018-01-01

Incorporation of concepts from landscape ecology into understanding and managing riverine ecosystems has become widely known as riverscape ecology. Riverscape ecology emphasizes interactions among processes at different scales and their consequences for valued ecosystem components, such as riverine fishes. Past studies have focused strongly on understanding the ecological processes in riverscapes and how human actions modify those processes. It is increasingly clear, however, that an understanding of the drivers behind actions that lead to human modification also merit consideration, especially regarding how those drivers influence management efficacy. These indirect drivers of riverscape outcomes can be understood in the context of a diverse array of social processes, which we collectively refer to as human dimensions. Like ecological phenomena, social processes also exhibit complex interactions across spatiotemporal scales. Greater emphasis on feedbacks between social and ecological processes will lead scientists and managers to more completely understand riverscapes as complex, dynamic, interacting social–ecological systems. Emerging applications in riverscapes, as well as studies of other ecosystems, provide examples that can lead to stronger integration of social and ecological science. We argue that conservation successes within riverscapes may not come from better ecological science, improved ecosystem service analyses, or even economic incentives if the fundamental drivers of human behaviors are not understood and addressed in conservation planning and implementation.

Understanding the complexities of Salmonella-host crosstalk as revealed by in vivo model organisms.

PubMed

Verma, Smriti; Srikanth, Chittur V

2015-07-01

Foodborne infections caused by non-typhoidal Salmonellae, such as Salmonella enterica serovar Typhimurium (ST), pose a major challenge in the developed and developing world. With constant rise of drug-resistant strains, understanding the epidemiology, microbiology, pathogenesis and host-pathogen interactions biology is a mandatory requirement to enable health systems to be ready to combat these illnesses. Patient data from hospitals, at least from some parts of the world, have aided in epidemiological understanding of ST-mediated disease. Most of the other aspects connected to Salmonella-host crosstalk have come from model systems that offer convenience, genetic tractability and low maintenance costs that make them extremely valuable tools. Complex model systems such as the bovine model have helped in understanding key virulence factors needed for infection. Simple systems such as fruit flies and Caenorhabditis elegans have aided in identification of novel virulence factors, host pathways and mechanistic details of interactions. Some of the path-breaking concepts of the field have come from mice model of ST colitis, which allows genetic manipulations as well as high degree of similarity to human counterpart. Together, they are invaluable for correlating in vitro findings of ST-induced disease progression in vivo. The current review is a compilation of various advances of ST-host interactions at cellular and molecular levels that has come from investigations involving model organisms. © 2015 International Union of Biochemistry and Molecular Biology.

Toward a multiscale modeling framework for understanding serotonergic function

PubMed Central

Wong-Lin, KongFatt; Wang, Da-Hui; Moustafa, Ahmed A; Cohen, Jeremiah Y; Nakamura, Kae

2017-01-01

Despite its importance in regulating emotion and mental wellbeing, the complex structure and function of the serotonergic system present formidable challenges toward understanding its mechanisms. In this paper, we review studies investigating the interactions between serotonergic and related brain systems and their behavior at multiple scales, with a focus on biologically-based computational modeling. We first discuss serotonergic intracellular signaling and neuronal excitability, followed by neuronal circuit and systems levels. At each level of organization, we will discuss the experimental work accompanied by related computational modeling work. We then suggest that a multiscale modeling approach that integrates the various levels of neurobiological organization could potentially transform the way we understand the complex functions associated with serotonin. PMID:28417684

Isolation of thylakoid membrane complexes from rice by a new double-strips BN/SDS-PAGE and bioinformatics prediction of stromal ridge subunits interaction.

PubMed

Shao, Jinzhen; Zhang, Yubo; Yu, Jianlan; Guo, Lin; Ding, Yi

2011-01-01

Thylakoid membrane complexes of rice (Oryza sativa L.) play crucial roles in growth and crop production. Understanding of protein interactions within the complex would provide new insights into photosynthesis. Here, a new "Double-Strips BN/SDS-PAGE" method was employed to separate thylakoid membrane complexes in order to increase the protein abundance on 2D-gels and to facilitate the identification of hydrophobic transmembrane proteins. A total of 58 protein spots could be observed and subunit constitution of these complexes exhibited on 2D-gels. The generality of this new approach was confirmed using thylakoid membrane from spinach (Spinacia oleracea) and pumpkin (Cucurita spp). Furthermore, the proteins separated from rice thylakoid membrane were identified by the mass spectrometry (MS). The stromal ridge proteins PsaD and PsaE were identified both in the holo- and core- PSI complexes of rice. Using molecular dynamics simulation to explore the recognition mechanism of these subunits, we showed that salt bridge interactions between residues R19 of PsaC and E168 of PasD as well as R75 of PsaC and E91 of PsaD played important roles in the stability of the complex. This stromal ridge subunits interaction was also supported by the subsequent analysis of the binding free energy, the intramolecular distances and the intramolecular energy.

Time to face the fats: what can mass spectrometry reveal about the structure of lipids and their interactions with proteins?

PubMed

Brown, Simon H J; Mitchell, Todd W; Oakley, Aaron J; Pham, Huong T; Blanksby, Stephen J

2012-09-01

Since the 1950s, X-ray crystallography has been the mainstay of structural biology, providing detailed atomic-level structures that continue to revolutionize our understanding of protein function. From recent advances in this discipline, a picture has emerged of intimate and specific interactions between lipids and proteins that has driven renewed interest in the structure of lipids themselves and raised intriguing questions as to the specificity and stoichiometry in lipid-protein complexes. Herein we demonstrate some of the limitations of crystallography in resolving critical structural features of ligated lipids and thus determining how these motifs impact protein binding. As a consequence, mass spectrometry must play an important and complementary role in unraveling the complexities of lipid-protein interactions. We evaluate recent advances and highlight ongoing challenges towards the twin goals of (1) complete structure elucidation of low, abundant, and structurally diverse lipids by mass spectrometry alone, and (2) assignment of stoichiometry and specificity of lipid interactions within protein complexes.

Time to Face the Fats: What Can Mass Spectrometry Reveal about the Structure of Lipids and Their Interactions with Proteins?

NASA Astrophysics Data System (ADS)

Brown, Simon H. J.; Mitchell, Todd W.; Oakley, Aaron J.; Pham, Huong T.; Blanksby, Stephen J.

2012-09-01

Since the 1950s, X-ray crystallography has been the mainstay of structural biology, providing detailed atomic-level structures that continue to revolutionize our understanding of protein function. From recent advances in this discipline, a picture has emerged of intimate and specific interactions between lipids and proteins that has driven renewed interest in the structure of lipids themselves and raised intriguing questions as to the specificity and stoichiometry in lipid-protein complexes. Herein we demonstrate some of the limitations of crystallography in resolving critical structural features of ligated lipids and thus determining how these motifs impact protein binding. As a consequence, mass spectrometry must play an important and complementary role in unraveling the complexities of lipid-protein interactions. We evaluate recent advances and highlight ongoing challenges towards the twin goals of (1) complete structure elucidation of low, abundant, and structurally diverse lipids by mass spectrometry alone, and (2) assignment of stoichiometry and specificity of lipid interactions within protein complexes.

Interactive social contagions and co-infections on complex networks

NASA Astrophysics Data System (ADS)

Liu, Quan-Hui; Zhong, Lin-Feng; Wang, Wei; Zhou, Tao; Eugene Stanley, H.

2018-01-01

What we are learning about the ubiquitous interactions among multiple social contagion processes on complex networks challenges existing theoretical methods. We propose an interactive social behavior spreading model, in which two behaviors sequentially spread on a complex network, one following the other. Adopting the first behavior has either a synergistic or an inhibiting effect on the spread of the second behavior. We find that the inhibiting effect of the first behavior can cause the continuous phase transition of the second behavior spreading to become discontinuous. This discontinuous phase transition of the second behavior can also become a continuous one when the effect of adopting the first behavior becomes synergistic. This synergy allows the second behavior to be more easily adopted and enlarges the co-existence region of both behaviors. We establish an edge-based compartmental method, and our theoretical predictions match well with the simulation results. Our findings provide helpful insights into better understanding the spread of interactive social behavior in human society.

Theoretical Study on Effects of Hydrogen-Bonding and Molecule-Cation Interactions on the Sensitivity of HMX.

PubMed

Li, Yunlu; Wu, Junpeng; Cao, Duanlin; Wang, Jianlong

2016-10-04

To assess the effects of weak interactions on the sensitivity of HMX, eleven complexes of HMX (where six of them are hydrogen-bonding complexes, and the other five are molecular-cation complexes) have been studied via quantum chemical treatment. The geometric and electronic structures were determined using DFT-B3LYP and MP2(full) methods with the 6-311++G(2df, 2p) and aug-cc-pVTZ basis sets. The changes of the bond dissociation energy (BDE) of the trigger bond (N-NO2 in HMX) and nitro group charge have been computed on the detail consideration to access the sensitivity changes of HMX. The results indicate that upon complex forming, the BDE increases and the charge of nitro group turns more negative in complexes, suggesting that the strength of the N-NO2 trigger bond is enhanced then the sensitivity of HMX is reduced. Atom-in-molecules analysis have also been carried to understand the nature of intermolecular interactions and the strength of trigger bonds.

Exploring Spaceship Earth

ERIC Educational Resources Information Center

McInnis, Noel F.

1973-01-01

Describes various activities to understand the nature of the earth as a spaceship and its impact on human life. A figure depicting a holocoenotic environmental complex is given which can be used to illustrate various interacting forces on earth. (PS)

Self-assembly of polyelectrolyte surfactant complexes using large scale MD simulation

NASA Astrophysics Data System (ADS)

Goswami, Monojoy; Sumpter, Bobby

2014-03-01

Polyelectrolytes (PE) and surfactants are known to form interesting structures with varied properties in aqueous solutions. The morphological details of the PE-surfactant complexes depend on a combination of polymer backbone, electrostatic interactions and hydrophobic interactions. We study the self-assembly of cationic PE and anionic surfactants complexes in dilute condition. The importance of such complexes of PE with oppositely charged surfactants can be found in biological systems, such as immobilization of enzymes in polyelectrolyte complexes or nonspecific association of DNA with protein. Many useful properties of PE surfactant complexes come from the highly ordered structures of surfactant self-assembly inside the PE aggregate which has applications in industry. We do large scale molecular dynamics simulation using LAMMPS to understand the structure and dynamics of PE-surfactant systems. Our investigation shows highly ordered pearl-necklace structures that have been observed experimentally in biological systems. We investigate many different properties of PE-surfactant complexation for different parameter ranges that are useful for pharmaceutical, engineering and biological applications.

Modeling and complexity of stochastic interacting Lévy type financial price dynamics

NASA Astrophysics Data System (ADS)

Wang, Yiduan; Zheng, Shenzhou; Zhang, Wei; Wang, Jun; Wang, Guochao

2018-06-01

In attempt to reproduce and investigate nonlinear dynamics of security markets, a novel nonlinear random interacting price dynamics, which is considered as a Lévy type process, is developed and investigated by the combination of lattice oriented percolation and Potts dynamics, which concerns with the instinctive random fluctuation and the fluctuation caused by the spread of the investors' trading attitudes, respectively. To better understand the fluctuation complexity properties of the proposed model, the complexity analyses of random logarithmic price return and corresponding volatility series are preformed, including power-law distribution, Lempel-Ziv complexity and fractional sample entropy. In order to verify the rationality of the proposed model, the corresponding studies of actual security market datasets are also implemented for comparison. The empirical results reveal that this financial price model can reproduce some important complexity features of actual security markets to some extent. The complexity of returns decreases with the increase of parameters γ1 and β respectively, furthermore, the volatility series exhibit lower complexity than the return series

Hydrologic, abiotic and biotic interactions: plant density, windspeed, leaf size and groundwater all affect oak water use efficiency

Treesearch

Darin J. Law; Deborah M. Finch

2011-01-01

Plant water use in drylands can be complex due to variation in hydrologic, abiotic and biotic factors, particularly near ephemeral or intermittent streams. Plant use of groundwater may be important but is usually uncertain. Disturbances like fire contribute to complex spatiotemporal heterogeneity. Improved understanding of how such hydrologic, abiotic, and biotic...

Understanding safety-critical interactions with a home medical device through Distributed Cognition.

PubMed

Rajkomar, Atish; Mayer, Astrid; Blandford, Ann

2015-08-01

As healthcare shifts from the hospital to the home, it is becoming increasingly important to understand how patients interact with home medical devices, to inform the safe and patient-friendly design of these devices. Distributed Cognition (DCog) has been a useful theoretical framework for understanding situated interactions in the healthcare domain. However, it has not previously been applied to study interactions with home medical devices. In this study, DCog was applied to understand renal patients' interactions with Home Hemodialysis Technology (HHT), as an example of a home medical device. Data was gathered through ethnographic observations and interviews with 19 renal patients and interviews with seven professionals. Data was analyzed through the principles summarized in the Distributed Cognition for Teamwork methodology. In this paper we focus on the analysis of system activities, information flows, social structures, physical layouts, and artefacts. By explicitly considering different ways in which cognitive processes are distributed, the DCog approach helped to understand patients' interaction strategies, and pointed to design opportunities that could improve patients' experiences of using HHT. The findings highlight the need to design HHT taking into consideration likely scenarios of use in the home and of the broader home context. A setting such as home hemodialysis has the characteristics of a complex and safety-critical socio-technical system, and a DCog approach effectively helps to understand how safety is achieved or compromised in such a system. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Understanding, creating, and managing complex techno-socio-economic systems: Challenges and perspectives

NASA Astrophysics Data System (ADS)

Helbing, D.; Balietti, S.; Bishop, S.; Lukowicz, P.

2011-05-01

This contribution reflects on the comments of Peter Allen [1], Bikas K. Chakrabarti [2], Péter Érdi [3], Juval Portugali [4], Sorin Solomon [5], and Stefan Thurner [6] on three White Papers (WP) of the EU Support Action Visioneer (www.visioneer.ethz.ch). These White Papers are entitled "From Social Data Mining to Forecasting Socio-Economic Crises" (WP 1) [7], "From Social Simulation to Integrative System Design" (WP 2) [8], and "How to Create an Innovation Accelerator" (WP 3) [9]. In our reflections, the need and feasibility of a "Knowledge Accelerator" is further substantiated by fundamental considerations and recent events around the globe. newpara The Visioneer White Papers propose research to be carried out that will improve our understanding of complex techno-socio-economic systems and their interaction with the environment. Thereby, they aim to stimulate multi-disciplinary collaborations between ICT, the social sciences, and complexity science. Moreover, they suggest combining the potential of massive real-time data, theoretical models, large-scale computer simulations and participatory online platforms. By doing so, it would become possible to explore various futures and to expand the limits of human imagination when it comes to the assessment of the often counter-intuitive behavior of these complex techno-socio-economic-environmental systems. In this contribution, we also highlight the importance of a pluralistic modeling approach and, in particular, the need for a fruitful interaction between quantitative and qualitative research approaches. newpara In an appendix we briefly summarize the concept of the FuturICT flagship project, which will build on and go beyond the proposals made by the Visioneer White Papers. EU flagships are ambitious multi-disciplinary high-risk projects with a duration of at least 10 years amounting to an envisaged overall budget of 1 billion EUR [10]. The goal of the FuturICT flagship initiative is to understand and manage complex, global, socially interactive systems, with a focus on sustainability and resilience.

Experimental evidence for blue-shifted hydrogen bonding in the fluoroform-hydrogen chloride complex: a matrix-isolation infrared and ab initio study.

PubMed

Gopi, R; Ramanathan, N; Sundararajan, K

2014-07-24

The 1:1 hydrogen-bonded complex of fluoroform and hydrogen chloride was studied using matrix-isolation infrared spectroscopy and ab initio computations. Using B3LYP and MP2 levels of theory with 6-311++G(d,p) and aug-cc-pVDZ basis sets, the structures of the complexes and their energies were computed. For the 1:1 CHF3-HCl complexes, ab initio computations showed two minima, one cyclic and the other acyclic. The cyclic complex was found to have C-H · · · Cl and C-F · · · H interactions, where CHF3 and HCl sub-molecules act as proton donor and proton acceptor, respectively. The second minimum corresponded to an acyclic complex stabilized only by the C-F · · · H interaction, in which CHF3 is the proton acceptor. Experimentally, we could trap the 1:1 CHF3-HCl cyclic complex in an argon matrix, where a blue-shift in the C-H stretching mode of the CHF3 sub-molecule was observed. To understand the nature of the interactions, Atoms in Molecules and Natural Bond Orbital analyses were carried out to unravel the reasons for blue-shifting of the C-H stretching frequency in these complexes.

Ecogeographic Genetic Epidemiology

PubMed Central

Sloan, Chantel D.; Duell, Eric J.; Shi, Xun; Irwin, Rebecca; Andrew, Angeline S.; Williams, Scott M.; Moore, Jason H.

2009-01-01

Complex diseases such as cancer and heart disease result from interactions between an individual's genetics and environment, i.e. their human ecology. Rates of complex diseases have consistently demonstrated geographic patterns of incidence, or spatial “clusters” of increased incidence relative to the general population. Likewise, genetic subpopulations and environmental influences are not evenly distributed across space. Merging appropriate methods from genetic epidemiology, ecology and geography will provide a more complete understanding of the spatial interactions between genetics and environment that result in spatial patterning of disease rates. Geographic Information Systems (GIS), which are tools designed specifically for dealing with geographic data and performing spatial analyses to determine their relationship, are key to this kind of data integration. Here the authors introduce a new interdisciplinary paradigm, ecogeographic genetic epidemiology, which uses GIS and spatial statistical analyses to layer genetic subpopulation and environmental data with disease rates and thereby discern the complex gene-environment interactions which result in spatial patterns of incidence. PMID:19025788

Intra- and inter-species interactions within biofilms of important foodborne bacterial pathogens

PubMed Central

Giaouris, Efstathios; Heir, Even; Desvaux, Mickaël; Hébraud, Michel; Møretrø, Trond; Langsrud, Solveig; Doulgeraki, Agapi; Nychas, George-John; Kačániová, Miroslava; Czaczyk, Katarzyna; Ölmez, Hülya; Simões, Manuel

2015-01-01

A community-based sessile life style is the normal mode of growth and survival for many bacterial species. Under such conditions, cell-to-cell interactions are inevitable and ultimately lead to the establishment of dense, complex and highly structured biofilm populations encapsulated in a self-produced extracellular matrix and capable of coordinated and collective behavior. Remarkably, in food processing environments, a variety of different bacteria may attach to surfaces, survive, grow, and form biofilms. Salmonella enterica, Listeria monocytogenes, Escherichia coli, and Staphylococcus aureus are important bacterial pathogens commonly implicated in outbreaks of foodborne diseases, while all are known to be able to create biofilms on both abiotic and biotic surfaces. Particularly challenging is the attempt to understand the complexity of inter-bacterial interactions that can be encountered in such unwanted consortia, such as competitive and cooperative ones, together with their impact on the final outcome of these communities (e.g., maturation, physiology, antimicrobial resistance, virulence, dispersal). In this review, up-to-date data on both the intra- and inter-species interactions encountered in biofilms of these pathogens are presented. A better understanding of these interactions, both at molecular and biophysical levels, could lead to novel intervention strategies for controlling pathogenic biofilm formation in food processing environments and thus improve food safety. PMID:26347727

A microscopic evaluation of collagen-bilirubin interactions: in vitro surface phenomenon.

PubMed

Usharani, N; Jayakumar, G C; Rao, J R; Chandrasekaran, B; Nair, B U

2014-02-01

This study is carried out to understand the morphology variations of collagen I matrices influenced by bilirubin. The characteristics of bilirubin interaction with collagen ascertained using various techniques like XRD, CLSM, fluorescence, SEM and AFM. These techniques are used to understand the distribution, expression and colocalization patterns of collagen-bilirubin complexes. The present investigation mimic the in vivo mechanisms created during the disorder condition like jaundice. Fluorescence technique elucidates the crucial role played by bilirubin deposition and interaction during collagen organization. Influence of bilirubin during collagen fibrillogenesis and banding patterns are clearly visualize using SEM. As a result, collagen-bilirubin complex provides different reconstructed patterns because of the influence of bilirubin concentration. Selectivity, specificity and spatial organization of collagen-bilirubin are determined through AFM imaging. Consequently, it is observed that the morphology and quantity of the bilirubin binding to collagen varied by the concentrations and the adsorption rate in protein solutions. Microscopic studies of collagen-bilirubin interaction confirms that bilirubin influence the fibrillogenesis and alter the rate of collagen organization depending on the bilirubin concentration. This knowledge helps to develop a novel drug to inhibit the interface point of interaction between collagen and bilirubin. © 2013 The Authors Journal of Microscopy © 2013 Royal Microscopical Society.

Interactive effects of large herbivores and plant diversity on insect abundance in a meadow steppe in China

Treesearch

Hui Zhu; Deli Wang; Qinfeng Guo; Jun Liu; Ling Wang

2015-01-01

The structure and dynamics of insect community in grasslands can be influenced by grazing management via altered characteristics of plant community. However, attempts to better understand the complex relationships among plants, insects, and large herbivores is still hampered largely by the interactive effects of plants, insects, and large grazers on each other. In this...

More stereotypes, please! The limits of 'theory of mind' and the need for further studies on the complexity of real world social interactions.

PubMed

Andrews, Kristin

2017-01-01

I suggest that the Stereotype Rationality Hypothesis (Jussim 2012) is only partially right. I agree it is rational to rely on stereotypes, but in the complexity of real world social interactions, most of our individuating information invokes additional stereotypes. Despite assumptions to the contrary, there is reason to think theory of mind is not accurate, and social psychology's denial of stereotype accuracy led us toward mindreading/theory of mind - a less accurate account of how we understand other people.

Emotional contagion and proto-organizing in human interaction dynamics

PubMed Central

Hazy, James K.; Boyatzis, Richard E.

2015-01-01

This paper combines the complexity notions of phase transitions and tipping points with recent advances in cognitive neuroscience to propose a general theory of human proto-organizing. It takes as a premise that a necessary prerequisite for organizing, or “proto-organizing,” occurs through emotional contagion in subpopulations of human interaction dynamics in complex ecosystems. Emotional contagion is posited to engender emotional understanding and identification with others, a social process that acts as a mechanism that enables (or precludes) cooperative responses to opportunities and risks. Propositions are offered and further research is suggested. PMID:26124736

Rational Design of Orthogonal Multipolar Interactions with Fluorine in Protein–Ligand Complexes

DOE PAGES

Pollock, Jonathan; Borkin, Dmitry; Lund, George; ...

2015-08-19

Multipolar interactions involving fluorine and the protein backbone have been frequently observed in protein–ligand complexes. Such fluorine–backbone interactions may substantially contribute to the high affinity of small molecule inhibitors. Here we found that introduction of trifluoromethyl groups into two different sites in the thienopyrimidine class of menin–MLL inhibitors considerably improved their inhibitory activity. In both cases, trifluoromethyl groups are engaged in short interactions with the backbone of menin. In order to understand the effect of fluorine, we synthesized a series of analogues by systematically changing the number of fluorine atoms, and we determined high-resolution crystal structures of the complexes withmore » menin. Here, we found that introduction of fluorine at favorable geometry for interactions with backbone carbonyls may improve the activity of menin–MLL inhibitors as much as 5- to 10-fold. In order to facilitate the design of multipolar fluorine–backbone interactions in protein–ligand complexes, we developed a computational algorithm named FMAP, which calculates fluorophilic sites in proximity to the protein backbone. We demonstrated that FMAP could be used to rationalize improvement in the activity of known protein inhibitors upon introduction of fluorine. Furthermore, FMAP may also represent a valuable tool for designing new fluorine substitutions and support ligand optimization in drug discovery projects. Analysis of the menin–MLL inhibitor complexes revealed that the backbone in secondary structures is particularly accessible to the interactions with fluorine. Lastly, considering that secondary structure elements are frequently exposed at protein interfaces, we postulate that multipolar fluorine–backbone interactions may represent a particularly attractive approach to improve inhibitors of protein–protein interactions.« less

MIiSR: Molecular Interactions in Super-Resolution Imaging Enables the Analysis of Protein Interactions, Dynamics and Formation of Multi-protein Structures.

PubMed

Caetano, Fabiana A; Dirk, Brennan S; Tam, Joshua H K; Cavanagh, P Craig; Goiko, Maria; Ferguson, Stephen S G; Pasternak, Stephen H; Dikeakos, Jimmy D; de Bruyn, John R; Heit, Bryan

2015-12-01

Our current understanding of the molecular mechanisms which regulate cellular processes such as vesicular trafficking has been enabled by conventional biochemical and microscopy techniques. However, these methods often obscure the heterogeneity of the cellular environment, thus precluding a quantitative assessment of the molecular interactions regulating these processes. Herein, we present Molecular Interactions in Super Resolution (MIiSR) software which provides quantitative analysis tools for use with super-resolution images. MIiSR combines multiple tools for analyzing intermolecular interactions, molecular clustering and image segmentation. These tools enable quantification, in the native environment of the cell, of molecular interactions and the formation of higher-order molecular complexes. The capabilities and limitations of these analytical tools are demonstrated using both modeled data and examples derived from the vesicular trafficking system, thereby providing an established and validated experimental workflow capable of quantitatively assessing molecular interactions and molecular complex formation within the heterogeneous environment of the cell.

Interaction Analysis of FABP4 Inhibitors by X-ray Crystallography and Fragment Molecular Orbital Analysis

PubMed Central

2016-01-01

X-ray crystal structural determination of FABP4 in complex with four inhibitors revealed the complex binding modes, and the resulting observations led to improvement of the inhibitory potency of FABP4 inhibitors. However, the detailed structure–activity relationship (SAR) could not be explained from these structural observations. For a more detailed understanding of the interactions between FABP4 and inhibitors, fragment molecular orbital analyses were performed. These analyses revealed that the total interfragment interaction energies of FABP4 and each inhibitor correlated with the ranking of the Ki value for the four inhibitors. Furthermore, interactions between each inhibitor and amino acid residues in FABP4 were identified. The oxygen atom of Lys58 in FABP4 was found to be very important for strong interactions with FABP4. These results might provide useful information for the development of novel potent FABP4 inhibitors. PMID:27096055

Interaction Analysis of FABP4 Inhibitors by X-ray Crystallography and Fragment Molecular Orbital Analysis.

PubMed

Tagami, Uno; Takahashi, Kazutoshi; Igarashi, Shunsuke; Ejima, Chieko; Yoshida, Tomomi; Takeshita, Sen; Miyanaga, Wataru; Sugiki, Masayuki; Tokumasu, Munetaka; Hatanaka, Toshihiro; Kashiwagi, Tatsuki; Ishikawa, Kohki; Miyano, Hiroshi; Mizukoshi, Toshimi

2016-04-14

X-ray crystal structural determination of FABP4 in complex with four inhibitors revealed the complex binding modes, and the resulting observations led to improvement of the inhibitory potency of FABP4 inhibitors. However, the detailed structure-activity relationship (SAR) could not be explained from these structural observations. For a more detailed understanding of the interactions between FABP4 and inhibitors, fragment molecular orbital analyses were performed. These analyses revealed that the total interfragment interaction energies of FABP4 and each inhibitor correlated with the ranking of the K i value for the four inhibitors. Furthermore, interactions between each inhibitor and amino acid residues in FABP4 were identified. The oxygen atom of Lys58 in FABP4 was found to be very important for strong interactions with FABP4. These results might provide useful information for the development of novel potent FABP4 inhibitors.

Dual-Color Click Beetle Luciferase Heteroprotein Fragment Complementation Assays

PubMed Central

Villalobos, Victor; Naik, Snehal; Bruinsma, Monique; Dothager, Robin S.; Pan, Mei-Hsiu; Samrakandi, Mustapha; Moss, Britney; Elhammali, Adnan; Piwnica-Worms, David

2010-01-01

Summary Understanding the functional complexity of protein interactions requires mapping biomolecular complexes within the cellular environment over biologically-relevant time scales. Herein we describe a novel set of reversible, multicolored heteroprotein complementation fragments based on various firefly and click beetle luciferases that utilize the same substrate, D-luciferin. Luciferase heteroprotein fragment complementation systems enabled dual-color quantification of two discreet pairs of interacting proteins simultaneously or two distinct proteins interacting with a third shared protein in live cells. Using real-time analysis of click beetle green and click beetle red luciferase heteroprotein fragment complementation applied to β-TrCP, an E3-ligase common to the regulation of both β-catenin and IκBα, GSK3β was identified as a novel candidate kinase regulating IκBα processing. These dual-color protein interaction switches may enable directed dynamic analysis of a variety of protein interactions in living cells. PMID:20851351

A geovisual analytic approach to understanding geo-social relationships in the international trade network.

PubMed

Luo, Wei; Yin, Peifeng; Di, Qian; Hardisty, Frank; MacEachren, Alan M

2014-01-01

The world has become a complex set of geo-social systems interconnected by networks, including transportation networks, telecommunications, and the internet. Understanding the interactions between spatial and social relationships within such geo-social systems is a challenge. This research aims to address this challenge through the framework of geovisual analytics. We present the GeoSocialApp which implements traditional network analysis methods in the context of explicitly spatial and social representations. We then apply it to an exploration of international trade networks in terms of the complex interactions between spatial and social relationships. This exploration using the GeoSocialApp helps us develop a two-part hypothesis: international trade network clusters with structural equivalence are strongly 'balkanized' (fragmented) according to the geography of trading partners, and the geographical distance weighted by population within each network cluster has a positive relationship with the development level of countries. In addition to demonstrating the potential of visual analytics to provide insight concerning complex geo-social relationships at a global scale, the research also addresses the challenge of validating insights derived through interactive geovisual analytics. We develop two indicators to quantify the observed patterns, and then use a Monte-Carlo approach to support the hypothesis developed above.

Ecophysiology meets conservation: understanding the role of disease in amphibian population declines

PubMed Central

Blaustein, Andrew R.; Gervasi, Stephanie S.; Johnson, Pieter T. J.; Hoverman, Jason T.; Belden, Lisa K.; Bradley, Paul W.; Xie, Gisselle Y.

2012-01-01

Infectious diseases are intimately associated with the dynamics of biodiversity. However, the role that infectious disease plays within ecological communities is complex. The complex effects of infectious disease at the scale of communities and ecosystems are driven by the interaction between host and pathogen. Whether or not a given host–pathogen interaction results in progression from infection to disease is largely dependent on the physiological characteristics of the host within the context of the external environment. Here, we highlight the importance of understanding the outcome of infection and disease in the context of host ecophysiology using amphibians as a model system. Amphibians are ideal for such a discussion because many of their populations are experiencing declines and extinctions, with disease as an important factor implicated in many declines and extinctions. Exposure to pathogens and the host's responses to infection can be influenced by many factors related to physiology such as host life history, immunology, endocrinology, resource acquisition, behaviour and changing climates. In our review, we discuss the relationship between disease and biodiversity. We highlight the dynamics of three amphibian host–pathogen systems that induce different effects on hosts and life stages and illustrate the complexity of amphibian–host–parasite systems. We then review links between environmental stress, endocrine–immune interactions, disease and climate change. PMID:22566676

A Geovisual Analytic Approach to Understanding Geo-Social Relationships in the International Trade Network

PubMed Central

Luo, Wei; Yin, Peifeng; Di, Qian; Hardisty, Frank; MacEachren, Alan M.

2014-01-01

The world has become a complex set of geo-social systems interconnected by networks, including transportation networks, telecommunications, and the internet. Understanding the interactions between spatial and social relationships within such geo-social systems is a challenge. This research aims to address this challenge through the framework of geovisual analytics. We present the GeoSocialApp which implements traditional network analysis methods in the context of explicitly spatial and social representations. We then apply it to an exploration of international trade networks in terms of the complex interactions between spatial and social relationships. This exploration using the GeoSocialApp helps us develop a two-part hypothesis: international trade network clusters with structural equivalence are strongly ‘balkanized’ (fragmented) according to the geography of trading partners, and the geographical distance weighted by population within each network cluster has a positive relationship with the development level of countries. In addition to demonstrating the potential of visual analytics to provide insight concerning complex geo-social relationships at a global scale, the research also addresses the challenge of validating insights derived through interactive geovisual analytics. We develop two indicators to quantify the observed patterns, and then use a Monte-Carlo approach to support the hypothesis developed above. PMID:24558409

Synergisms between microbial pathogens in plant disease complexes: a growing trend

PubMed Central

Lamichhane, Jay Ram; Venturi, Vittorio

2015-01-01

Plant diseases are often thought to be caused by one species or even by a specific strain. Microbes in nature, however, mostly occur as part of complex communities and this has been noted since the time of van Leeuwenhoek. Interestingly, most laboratory studies focus on single microbial strains grown in pure culture; we were therefore unaware of possible interspecies and/or inter-kingdom interactions of pathogenic microbes in the wild. In human and animal infections, it is now being recognized that many diseases are the result of multispecies synergistic interactions. This increases the complexity of the disease and has to be taken into consideration in the development of more effective control measures. On the other hand, there are only a few reports of synergistic pathogen–pathogen interactions in plant diseases and the mechanisms of interactions are currently unknown. Here we review some of these reports of synergism between different plant pathogens and their possible implications in crop health. Finally, we briefly highlight the recent technological advances in diagnostics as these are beginning to provide important insights into the microbial communities associated with complex plant diseases. These examples of synergistic interactions of plant pathogens that lead to disease complexes might prove to be more common than expected and understanding the underlying mechanisms might have important implications in plant disease epidemiology and management. PMID:26074945

Connected Worlds: Connecting the public with complex environmental systems

NASA Astrophysics Data System (ADS)

Uzzo, S. M.; Chen, R. S.; Downs, R. R.

2016-12-01

Among the most important concepts in environmental science learning is the structure and dynamics of coupled human and natural systems (CHANS). But the fundamental epistemology for understanding CHANS requires systems thinking, interdisciplinarity, and complexity. Although the Next Generation Science Standards mandate connecting ideas across disciplines and systems, traditional approaches to education do not provide more than superficial understanding of this concept. Informal science learning institutions have a key role in bridging gaps between the reductive nature of classroom learning and contemporary data-driven science. The New York Hall of Science, in partnership with Design I/O and Columbia University's Center for International Earth Science Information Network, has developed an approach to immerse visitors in complex human nature interactions and provide opportunities for those of all ages to elicit and notice environmental consequences of their actions. Connected Worlds is a nearly 1,000 m2 immersive, playful environment in which students learn about complexity and interconnectedness in ecosystems and how ecosystems might respond to human intervention. It engages students through direct interactions with fanciful flora and fauna within and among six biomes: desert, rainforest, grassland, mountain valley, reservoir, and wetlands, which are interconnected through stocks and flows of water. Through gestures and the manipulation of a dynamic water system, Connected Worlds enables students, teachers, and parents to experience how the ecosystems of planet Earth are connected and to observe relationships between the behavior of Earth's inhabitants and our shared world. It is also a cyberlearning platform to study how visitors notice and scaffold their understanding of complex environmental processes and the responses of these processes to human intervention, to help inform the improvement of education practices in complex environmental science.

Dynamics of Charged Species in Ionic-Neutral Block Copolymer and Surfactant Complexes [Structural Relaxation and Dynamics of Ionic-Neutral Block Copolymer Surfactant Complexes

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

Borreguero, Jose M.; Pincus, Philip A.; Sumpter, Bobby G.

Structure–property relationships of ionic block copolymer (BCP) surfactant complexes are critical toward the progress of favorable engineering design of efficient charge-transport materials. In this paper, molecular dynamics simulations are used to understand the dynamics of charged-neutral BCP and surfactant complexes. The dynamics are examined for two different systems: charged-neutral double-hydrophilic and hydrophobic–hydrophilic block copolymers with oppositely charged surfactant moieties. The dynamics of the surfactant head, tails, and charges are studied for five different BCP volume fractions. We observe that the dynamics of the different species solely depend on the balance between electrostatic and entropic interactions between the charged species andmore » the neutral monomers. The favorable hydrophobic–hydrophobic interactions and the unfavorable hydrophobic–hydrophilic interactions determine the mobilities of the monomers. The dynamical properties of the charge species influence complex formation. Structural relaxations exhibit length-scale dependent behavior, with slower relaxation at the radius of gyration length-scale and faster relaxation at the segmental length-scale, consistent with previous results. The dynamical analysis correlates ion-exchange kinetics to the self-assembly behavior of the complexes.« less

Dynamics of Charged Species in Ionic-Neutral Block Copolymer and Surfactant Complexes [Structural Relaxation and Dynamics of Ionic-Neutral Block Copolymer Surfactant Complexes

DOE PAGES

Borreguero, Jose M.; Pincus, Philip A.; Sumpter, Bobby G.; ...

2017-06-21

Structure–property relationships of ionic block copolymer (BCP) surfactant complexes are critical toward the progress of favorable engineering design of efficient charge-transport materials. In this paper, molecular dynamics simulations are used to understand the dynamics of charged-neutral BCP and surfactant complexes. The dynamics are examined for two different systems: charged-neutral double-hydrophilic and hydrophobic–hydrophilic block copolymers with oppositely charged surfactant moieties. The dynamics of the surfactant head, tails, and charges are studied for five different BCP volume fractions. We observe that the dynamics of the different species solely depend on the balance between electrostatic and entropic interactions between the charged species andmore » the neutral monomers. The favorable hydrophobic–hydrophobic interactions and the unfavorable hydrophobic–hydrophilic interactions determine the mobilities of the monomers. The dynamical properties of the charge species influence complex formation. Structural relaxations exhibit length-scale dependent behavior, with slower relaxation at the radius of gyration length-scale and faster relaxation at the segmental length-scale, consistent with previous results. The dynamical analysis correlates ion-exchange kinetics to the self-assembly behavior of the complexes.« less

nES GEMMA Analysis of Lectins and Their Interactions with Glycoproteins - Separation, Detection, and Sampling of Noncovalent Biospecific Complexes

NASA Astrophysics Data System (ADS)

Engel, Nicole Y.; Weiss, Victor U.; Marchetti-Deschmann, Martina; Allmaier, Günter

2017-01-01

In order to better understand biological events, lectin-glycoprotein interactions are of interest. The possibility to gather more information than the mere positive or negative response for interactions brought mass spectrometry into the center of many research fields. The presented work shows the potential of a nano-electrospray gas-phase electrophoretic mobility molecular analyzer (nES GEMMA) to detect weak, noncovalent, biospecific interactions besides still unbound glycoproteins and unreacted lectins without prior liquid phase separation. First results for Sambucus nigra agglutinin, concanavalin A, and wheat germ agglutinin and their retained noncovalent interactions with glycoproteins in the gas phase are presented. Electrophoretic mobility diameters (EMDs) were obtained by nES GEMMA for all interaction partners correlating very well with molecular masses determined by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) of the individual molecules. Moreover, EMDs measured for the lectin-glycoprotein complexes were in good accordance with theoretically calculated mass values. Special focus was laid on complex formation for different lectin concentrations and binding specificities to evaluate the method with respect to results obtained in the liquid phase. The latter was addressed by capillary electrophoresis on-a-chip (CE-on-a-chip). Of exceptional interest was the fact that the formed complexes could be sampled according to their size onto nitrocellulose membranes after gas-phase separation. Subsequent immunological investigation further proved that the collected complex actually retained its native structure throughout nES GEMMA analysis and sampling.

Docking and free energy simulations to predict conformational domains involved in hCG-LH receptor interactions using recombinant antibodies.

PubMed

Majumdar, Ritankar; Railkar, Reema; Dighe, Rajan R

2011-11-01

Single chain fragment variables (ScFvs) have been extensively employed in studying the protein-protein interactions. ScFvs derived from phage display libraries have an additional advantage of being generated against a native antigen, circumventing loss of information on conformational epitopes. In the present study, an attempt has been made to elucidate human chorionic gonadotropin (hCG)-luteinizing hormone (LH) receptor interactions by using a neutral and two inhibitory ScFvs against hCG. The objective was to dock a computationally derived model of these ScFvs onto the crystal structure of hCG and understand the differential roles of the mapped epitopes in hCG-LH receptor interactions. An anti-hCG ScFv, whose epitope was mapped previously using biochemical tools, served as the positive control for assessing the quality of docking analysis. To evaluate the role of specific side chains at the hCG-ScFv interface, binding free energy as well as residue interaction energies of complexes in solution were calculated using molecular mechanics Poisson-Boltzmann/surface area method after performing the molecular dynamic simulations on the selected hCG-ScFv models and validated using biochemical and SPR analysis. The robustness of these calculations was demonstrated by comparing the theoretically determined binding energies with the experimentally obtained kinetic parameters for hCG-ScFv complexes. Superimposition of hCG-ScFv model onto a model of hCG complexed with the 51-266 residues of LH receptor revealed importance of the residues previously thought to be unimportant for hormone binding and response. This analysis provides an alternate tool for understanding the structure-function analysis of ligand-receptor interactions. Copyright © 2011 Wiley-Liss, Inc.

Understanding social complexity within the wildland urban interface: A new species of human habitation? Environmental Management

Treesearch

Travis B. Paveglio; Pamela J. Jakes; Matthew S. Carroll; Daniel R. Williams

2009-01-01

The lack of knowledge regarding social diversity in the Wildland Urban Interface (WUI) or an in-depth understanding of the ways people living there interact to address common problems is concerning, perhaps even dangerous, given that community action is necessary for successful wildland fire preparedness and natural resource management activities. In this article, we...

Understanding the value of mixed methods research: the Children's Safety Initiative-Emergency Medical Services.

PubMed

Hansen, Matthew; O'Brien, Kerth; Meckler, Garth; Chang, Anna Marie; Guise, Jeanne-Marie

2016-07-01

Mixed methods research has significant potential to broaden the scope of emergency care and specifically emergency medical services investigation. Mixed methods studies involve the coordinated use of qualitative and quantitative research approaches to gain a fuller understanding of practice. By combining what is learnt from multiple methods, these approaches can help to characterise complex healthcare systems, identify the mechanisms of complex problems such as medical errors and understand aspects of human interaction such as communication, behaviour and team performance. Mixed methods approaches may be particularly useful for out-of-hospital care researchers because care is provided in complex systems where equipment, interpersonal interactions, societal norms, environment and other factors influence patient outcomes. The overall objectives of this paper are to (1) introduce the fundamental concepts and approaches of mixed methods research and (2) describe the interrelation and complementary features of the quantitative and qualitative components of mixed methods studies using specific examples from the Children's Safety Initiative-Emergency Medical Services (CSI-EMS), a large National Institutes of Health-funded research project conducted in the USA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Meeting Report: Structural Determination of Environmentally Responsive Proteins

PubMed Central

Reinlib, Leslie

2005-01-01

The three-dimensional structure of gene products continues to be a missing lynchpin between linear genome sequences and our understanding of the normal and abnormal function of proteins and pathways. Enhanced activity in this area is likely to lead to better understanding of how discrete changes in molecular patterns and conformation underlie functional changes in protein complexes and, with it, sensitivity of an individual to an exposure. The National Institute of Environmental Health Sciences convened a workshop of experts in structural determination and environmental health to solicit advice for future research in structural resolution relative to environmentally responsive proteins and pathways. The highest priorities recommended by the workshop were to support studies of structure, analysis, control, and design of conformational and functional states at molecular resolution for environmentally responsive molecules and complexes; promote understanding of dynamics, kinetics, and ligand responses; investigate the mechanisms and steps in posttranslational modifications, protein partnering, impact of genetic polymorphisms on structure/function, and ligand interactions; and encourage integrated experimental and computational approaches. The workshop participants also saw value in improving the throughput and purity of protein samples and macromolecular assemblies; developing optimal processes for design, production, and assembly of macromolecular complexes; encouraging studies on protein–protein and macromolecular interactions; and examining assemblies of individual proteins and their functions in pathways of interest for environmental health. PMID:16263521

Multi-Dimensional Scaling based grouping of known complexes and intelligent protein complex detection.

PubMed

Rehman, Zia Ur; Idris, Adnan; Khan, Asifullah

2018-06-01

Protein-Protein Interactions (PPI) play a vital role in cellular processes and are formed because of thousands of interactions among proteins. Advancements in proteomics technologies have resulted in huge PPI datasets that need to be systematically analyzed. Protein complexes are the locally dense regions in PPI networks, which extend important role in metabolic pathways and gene regulation. In this work, a novel two-phase protein complex detection and grouping mechanism is proposed. In the first phase, topological and biological features are extracted for each complex, and prediction performance is investigated using Bagging based Ensemble classifier (PCD-BEns). Performance evaluation through cross validation shows improvement in comparison to CDIP, MCode, CFinder and PLSMC methods Second phase employs Multi-Dimensional Scaling (MDS) for the grouping of known complexes by exploring inter complex relations. It is experimentally observed that the combination of topological and biological features in the proposed approach has greatly enhanced prediction performance for protein complex detection, which may help to understand various biological processes, whereas application of MDS based exploration may assist in grouping potentially similar complexes. Copyright © 2018 Elsevier Ltd. All rights reserved.

In Silico Analysis for the Study of Botulinum Toxin Structure

NASA Astrophysics Data System (ADS)

Suzuki, Tomonori; Miyazaki, Satoru

2010-01-01

Protein-protein interactions play many important roles in biological function. Knowledge of protein-protein complex structure is required for understanding the function. The determination of protein-protein complex structure by experimental studies remains difficult, therefore computational prediction of protein structures by structure modeling and docking studies is valuable method. In addition, MD simulation is also one of the most popular methods for protein structure modeling and characteristics. Here, we attempt to predict protein-protein complex structure and property using some of bioinformatic methods, and we focus botulinum toxin complex as target structure.

Biomedically relevant chemical and physical properties of coal combustion products.

PubMed Central

Fisher, G L

1983-01-01

The evaluation of the potential public and occupational health hazards of developing and existing combustion processes requires a detailed understanding of the physical and chemical properties of effluents available for human and environmental exposures. These processes produce complex mixtures of gases and aerosols which may interact synergistically or antagonistically with biological systems. Because of the physicochemical complexity of the effluents, the biomedically relevant properties of these materials must be carefully assessed. Subsequent to release from combustion sources, environmental interactions further complicate assessment of the toxicity of combustion products. This report provides an overview of the biomedically relevant physical and chemical properties of coal fly ash. Coal fly ash is presented as a model complex mixture for health and safety evaluation of combustion processes. PMID:6337824

Recent progress toward the identification of anti-viral immune mechanisms in decapod crustaceans.

PubMed

Hauton, Chris

2017-07-01

The sustainable intensification of crustacean aquaculture, which is dominated by the farming of penaeid shrimp species, continues to be beset by viral disease outbreaks. Despite this, reports exist of differential susceptibility to viral infection between different shrimp species and populations, and between shrimp and other decapod crustaceans. These reports have, in part, provided the motivation to identify key mechanisms of antiviral resistance, or refractivity, in commercially-important species. Within the last decade these studies have created significant advances in our understanding of host virus interactions in decapod models. However, at the same time, the complexity of host virus interactions has presented significant challenges for interpretation of anti-viral immune responses. In this short review, recent progress in our understanding of the complexity of host virus interactions are considered, and challenges to the unequivocal identification of anti-viral immunity are highlighted. Special consideration is given to the advances in understanding being created by the use of RNA interference approaches. Based on the 'state of the art', it is concluded that the identification of effective intervention strategies for application at farm scale currently presents an unrealistic target for the aquaculture industry. Future technical developments necessary to support continued progress are also considered. Copyright © 2017 Elsevier Inc. All rights reserved.

Membrane Interaction of Antimicrobial Peptides Using E. coli Lipid Extract as Model Bacterial Cell Membranes and SFG Spectroscopy

PubMed Central

Soblosky, Lauren; Ramamoorthy, Ayyalusamy; Chen, Zhan

2015-01-01

Supported lipid bilayers are used as a convenient model cell membrane system to study biologically important molecule-lipid interactions in situ. However, the lipid bilayer models are often simple and the acquired results with these models may not provide all pertinent information related to a real cell membrane. In this work, we use sum frequency generation (SFG) vibrational spectroscopy to study molecular-level interactions between the antimicrobial peptides (AMPs) MSI-594, ovispirin-1 G18, magainin 2 and a simple 1,2-dipalmitoyl-d62-sn-glycero-3-phosphoglycerol (dDPPG)-1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) bilayer. We compared such interactions to those between the AMPs and a more complex dDPPG/E. coli polar lipid extract bilayer. We show that to fully understand more complex aspects of peptide-bilayer interaction, such as interaction kinetics, a heterogeneous lipid composition is required, such as the E. coli polar lipid extract. The discrepancy in peptide-bilayer interaction is likely due in part to the difference in bilayer charge between the two systems since highly negative charged lipids can promote more favorable electrostatic interactions between the peptide and lipid bilayer. Results presented in this paper indicate that more complex model bilayers are needed to accurately analyze peptide-cell membrane interactions and demonstrates the importance of using an appropriate lipid composition to study AMP interaction properties. PMID:25707312

Predator diversity and environmental change modify the strengths of trophic and nontrophic interactions.

PubMed

Sentis, Arnaud; Gémard, Charlène; Jaugeon, Baptiste; Boukal, David S

2017-07-01

Understanding the dependence of species interaction strengths on environmental factors and species diversity is crucial to predict community dynamics and persistence in a rapidly changing world. Nontrophic (e.g. predator interference) and trophic components together determine species interaction strengths, but the effects of environmental factors on these two components remain largely unknown. This impedes our ability to fully understand the links between environmental drivers and species interactions. Here, we used a dynamical modelling framework based on measured predator functional responses to investigate the effects of predator diversity, prey density, and temperature on trophic and nontrophic interaction strengths within a freshwater food web. We found that (i) species interaction strengths cannot be predicted from trophic interactions alone, (ii) nontrophic interaction strengths vary strongly among predator assemblages, (iii) temperature has opposite effects on trophic and nontrophic interaction strengths, and (iv) trophic interaction strengths decrease with prey density, whereas the dependence of nontrophic interaction strengths on prey density is concave up. Interestingly, the qualitative impacts of temperature and prey density on the strengths of trophic and nontrophic interactions were independent of predator identity, suggesting a general pattern. Our results indicate that taking multiple environmental factors and the nonlinearity of density-dependent species interactions into account is an important step towards a better understanding of the effects of environmental variations on complex ecological communities. The functional response approach used in this study opens new avenues for (i) the quantification of the relative importance of the trophic and nontrophic components in species interactions and (ii) a better understanding how environmental factors affect these interactions and the dynamics of ecological communities. © 2016 John Wiley & Sons Ltd.

Structural Evidence for the Tetrameric Assembly of Chemokine CCL11 and the Glycosaminoglycan Arixtra™

PubMed Central

Dykstra, Andrew B.; Sweeney, Matt D.; Leary, Julie A.

2013-01-01

Understanding chemokine interactions with glycosaminoglycans (GAG) is critical as these interactions have been linked to a number of inflammatory medical conditions, such as arthritis and asthma. To better characterize in vivo protein function, comprehensive knowledge of multimeric species, formed by chemokines under native conditions, is necessary. Herein is the first report of a tetrameric assembly of the human chemokine CCL11, which was shown bound to the GAG Arixtra™. Isothermal titration calorimetry data indicated that CCL11 interacts with Arixtra, and ion mobility mass spectrometry (IM-MS) was used to identify ions corresponding to the CCL11 tetrameric species bound to Arixtra. Collisional cross sections (CCS) of the CCL11 tetramer-Arixtra noncovalent complex were compared to theoretical CCS values calculated using a preliminary structure of the complex deduced using X-ray crystallography. Experimental CCS values were in agreement with theoretical values, strengthening the IM-MS evidence for the formation of the noncovalent complex. Tandem mass spectrometry data of the complex indicated that the tetramer-GAG complex dissociates into a monomer and a trimer-GAG species, suggesting that two CC-like dimers are bridged by Arixtra. As development of chemokine inhibitors is of utmost importance to treatment of medical inflammatory conditions, these results provide vital insights into chemokine-GAG interactions. PMID:24970196

Structural Evidence for the Tetrameric Assembly of Chemokine CCL11 and the Glycosaminoglycan Arixtra™.

PubMed

Dykstra, Andrew B; Sweeney, Matt D; Leary, Julie A

2013-11-06

Understanding chemokine interactions with glycosaminoglycans (GAG) is critical as these interactions have been linked to a number of inflammatory medical conditions, such as arthritis and asthma. To better characterize in vivo protein function, comprehensive knowledge of multimeric species, formed by chemokines under native conditions, is necessary. Herein is the first report of a tetrameric assembly of the human chemokine CCL11, which was shown bound to the GAG Arixtra™. Isothermal titration calorimetry data indicated that CCL11 interacts with Arixtra, and ion mobility mass spectrometry (IM-MS) was used to identify ions corresponding to the CCL11 tetrameric species bound to Arixtra. Collisional cross sections (CCS) of the CCL11 tetramer-Arixtra noncovalent complex were compared to theoretical CCS values calculated using a preliminary structure of the complex deduced using X-ray crystallography. Experimental CCS values were in agreement with theoretical values, strengthening the IM-MS evidence for the formation of the noncovalent complex. Tandem mass spectrometry data of the complex indicated that the tetramer-GAG complex dissociates into a monomer and a trimer-GAG species, suggesting that two CC-like dimers are bridged by Arixtra. As development of chemokine inhibitors is of utmost importance to treatment of medical inflammatory conditions, these results provide vital insights into chemokine-GAG interactions.

Analysis of DNA interactions using single-molecule force spectroscopy.

PubMed

Ritzefeld, Markus; Walhorn, Volker; Anselmetti, Dario; Sewald, Norbert

2013-06-01

Protein-DNA interactions are involved in many biochemical pathways and determine the fate of the corresponding cell. Qualitative and quantitative investigations on these recognition and binding processes are of key importance for an improved understanding of biochemical processes and also for systems biology. This review article focusses on atomic force microscopy (AFM)-based single-molecule force spectroscopy and its application to the quantification of forces and binding mechanisms that lead to the formation of protein-DNA complexes. AFM and dynamic force spectroscopy are exciting tools that allow for quantitative analysis of biomolecular interactions. Besides an overview on the method and the most important immobilization approaches, the physical basics of the data evaluation is described. Recent applications of AFM-based force spectroscopy to investigate DNA intercalation, complexes involving DNA aptamers and peptide- and protein-DNA interactions are given.

Correlative nanoscale imaging of actin filaments and their complexes

NASA Astrophysics Data System (ADS)

Sharma, Shivani; Zhu, Huanqi; Grintsevich, Elena E.; Reisler, Emil; Gimzewski, James K.

2013-06-01

Actin remodeling is an area of interest in biology in which correlative microscopy can bring a new way to analyze protein complexes at the nanoscale. Advances in EM, X-ray diffraction, fluorescence, and single molecule techniques have provided a wealth of information about the modulation of the F-actin structure and its regulation by actin binding proteins (ABPs). Yet, there are technological limitations of these approaches to achieving quantitative molecular level information on the structural and biophysical changes resulting from ABPs interaction with F-actin. Fundamental questions about the actin structure and dynamics and how these determine the function of ABPs remain unanswered. Specifically, how local and long-range structural and conformational changes result in ABPs induced remodeling of F-actin needs to be addressed at the single filament level. Advanced, sensitive and accurate experimental tools for detailed understanding of ABP-actin interactions are much needed. This article discusses the current understanding of nanoscale structural and mechanical modulation of F-actin by ABPs at the single filament level using several correlative microscopic techniques, focusing mainly on results obtained by Atomic Force Microscopy (AFM) analysis of ABP-actin complexes.

Understanding Nucleic Acid–Ion Interactions

PubMed Central

Lipfert, Jan; Doniach, Sebastian; Das, Rhiju; Herschlag, Daniel

2015-01-01

Ions surround nucleic acids in what is referred to as an ion atmosphere. As a result, the folding and dynamics of RNA and DNA and their complexes with proteins and with each other cannot be understood without a reasonably sophisticated appreciation of these ions’ electrostatic interactions. However, the underlying behavior of the ion atmosphere follows physical rules that are distinct from the rules of site binding that biochemists are most familiar and comfortable with. The main goal of this review is to familiarize nucleic acid experimentalists with the physical concepts that underlie nucleic acid–ion interactions. Throughout, we provide practical strategies for interpreting and analyzing nucleic acid experiments that avoid pitfalls from oversimplified or incorrect models. We briefly review the status of theories that predict or simulate nucleic acid–ion interactions and experiments that test these theories. Finally, we describe opportunities for going beyond phenomenological fits to a next-generation, truly predictive understanding of nucleic acid–ion interactions. PMID:24606136

Structure-Function Based Molecular Relationships in Ewing's Sarcoma

PubMed Central

2015-01-01

Ewing's Sarcoma Oncogene (ews) on chromosome 22q12 is encoding a ubiquitously expressed RNA-binding protein (EWS) with unknown function that is target of tumor-specific chromosomal translocations in Ewing's sarcoma family of tumors. A model of transcription complex was proposed in which the heterodimer Rpb4/7 binds to EAD, connecting it to Core RNA Pol II. The DNA-binding domain, provided by EFP, is bound to the promoter. Rpb4/7 binds RNA, stabilizing the transcription complex. The complex Rpb4/7 can stabilize the preinitiation complexes by converting the conformation of RNA Pol II. EWS may change its conformation, so that NTD becomes accessible. Two different mechanisms of interaction between EWS and RNA Pol II are proposed: (I) an intermolecular EWS-EWS interaction between two molecules, pushing conformation from “closed” to “open” state, or (II) an intramolecular interaction inside the molecule of EWS, pushing conformation of the molecule from “closed” to “open” state. The modified forms of EWS may interact with Pol II subunits hsRpb5 and hsRpb7. The EWS and EFPs binding partners are described schematically in a model, an attempt to link the transcription with the splicing. The proposed model helps to understand the functional molecular interactions in cancer, to find new partners and ways to treat cancer. PMID:25688366

Moving college students to a better understanding of substrate specificity of enzymes through utilizing multimedia pre-training and an interactive enzyme model

NASA Astrophysics Data System (ADS)

Saleh, Mounir R.

Scientists' progress in understanding enzyme specificity uncovered a complex natural phenomenon. However, not all of the currently available biology textbooks seem to be up to date on this progress. Students' understanding of how enzymes work is a core requirement in biochemistry and biology tertiary education. Nevertheless, current pre-college science education does not provide students with enough biochemical background to enable them to understand complex material such as this. To bridge this gap, a multimedia pre-training presentation was prepared to fuel the learner's prior knowledge with discrete facts necessary to understand the presented concept. This treatment is also known to manage intrinsic cognitive load during the learning process. An interactive instructional enzyme model was also built to motivate students to learn about substrate specificity of enzymes. Upon testing the effect of this combined treatment on 111 college students, desirable learning outcomes were found in terms of cognitive load, motivation, and achievement. The multimedia pre-training group reported significantly less intrinsic cognitive load, higher motivation, and demonstrated higher transfer performance than the control and post-training groups. In this study, a statistical mediation model is also proposed to explain how cognitive load and motivation work in concert to foster learning from multimedia pre-training. This type of research goes beyond simple forms of "what works" to a deeper understanding of "how it works", thus enabling informed decisions for multimedia instructional design. Multimedia learning plays multiple roles in science education. Therefore, science learners would be some of the first to benefit from improving multimedia instructional design. Accordingly, complex scientific phenomena can be introduced to college students in a motivating, informative, and cognitively efficient learning environment.

Contribution of parenting to complex syntax development in preschool children with developmental delays or typical development.

PubMed

Moody, C T; Baker, B L; Blacher, J

2018-05-10

Despite studies of how parent-child interactions relate to early child language development, few have examined the continued contribution of parenting to more complex language skills through the preschool years. The current study explored how positive and negative parenting behaviours relate to growth in complex syntax learning from child age 3 to age 4 years, for children with typical development or developmental delays (DDs). Participants were children with or without DD (N = 60) participating in a longitudinal study of development. Parent-child interactions were transcribed and coded for parenting domains and child language. Multiple regression analyses were used to identify the contribution of parenting to complex syntax growth in children with typical development or DD. Analyses supported a final model, F(9,50) = 11.90, P < .001, including a significant three-way interaction between positive parenting behaviours, negative parenting behaviours and child delay status. This model explained 68.16% of the variance in children's complex syntax at age 4. Simple two-way interactions indicated differing effects of parenting variables for children with or without DD. Results have implications for understanding of complex syntax acquisition in young children, as well as implications for interventions. © 2018 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Affinity purification combined with mass spectrometry to identify herpes simplex virus protein-protein interactions.

PubMed

Meckes, David G

2014-01-01

The identification and characterization of herpes simplex virus protein interaction complexes are fundamental to understanding the molecular mechanisms governing the replication and pathogenesis of the virus. Recent advances in affinity-based methods, mass spectrometry configurations, and bioinformatics tools have greatly increased the quantity and quality of protein-protein interaction datasets. In this chapter, detailed and reliable methods that can easily be implemented are presented for the identification of protein-protein interactions using cryogenic cell lysis, affinity purification, trypsin digestion, and mass spectrometry.

Mapping protein-DNA and protein-protein interactions of ATP-dependent chromatin remodelers.

PubMed

Hota, Swetansu K; Dechassa, Mekonnen Lemma; Prasad, Punit; Bartholomew, Blaine

2012-01-01

Chromatin plays a key regulatory role in several DNA-dependent processes as it regulates DNA access to different protein factors. Several multisubunit protein complexes interact, modify, or mobilize nucleosomes: the basic unit of chromatin, from its original location in an ATP-dependent manner to facilitate processes, such as transcription, replication, repair, and recombination. Knowledge of the interactions of chromatin remodelers with nucleosomes is a crucial requirement to understand the mechanism of chromatin remodeling. Here, we describe several methods to analyze the interactions of multisubunit chromatin-remodeling enzymes with nucleosomes.

Crystallographic study of FABP5 as an intracellular endocannabinoid transporter

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

Sanson, Benoît; Wang, Tao; Sun, Jing

2014-02-01

FABP5 was recently found to intracellularly transport endocannabinoid signaling lipids. The structures of FABP5 complexed with two endocannabinoids and an inhibitor were solved. Human FABP5 was found to dimerize via a domain-swapping mechanism. This work will help in the development of inhibitors to raise endocannabinoid levels. In addition to binding intracellular fatty acids, fatty-acid-binding proteins (FABPs) have recently been reported to also transport the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG), arachidonic acid derivatives that function as neurotransmitters and mediate a diverse set of physiological and psychological processes. To understand how the endocannabinoids bind to FABPs, the crystal structures of FABP5more » in complex with AEA, 2-AG and the inhibitor BMS-309403 were determined. These ligands are shown to interact primarily with the substrate-binding pocket via hydrophobic interactions as well as a common hydrogen bond to the Tyr131 residue. This work advances our understanding of FABP5–endocannabinoid interactions and may be useful for future efforts in the development of small-molecule inhibitors to raise endocannabinoid levels.« less

Effect of Methyl Substitution on the N-H···O Interaction in Complexes of Pyrrole with Water, Methanol, and Dimethyl Ether: Matrix Isolation Infrared Spectroscopy and ab Initio Computational Studies.

PubMed

Sarkar, Shubhra; Ramanathan, N; Sundararajan, K

2018-03-08

Hydrogen-bonded interactions of pyrrole with water and methanol have been studied using matrix isolation infrared spectroscopy and compared with the calculation performed on dimethyl ether. Computations carried out at MP2/aug-cc-pVDZ level of theory yielded two minima for the pyrrole-water and pyrrole-methanol complexes. The global and local minima correspond to the N-H···O and O-H···π complexes, respectively, where the N-H group of pyrrole interacts with oxygen of water/methanol and O-H of water and methanol interacts with the π cloud of pyrrole. Computations performed on the pyrrole-dimethyl ether gave only N-H···O type complex. From the experimental vibrational wavenumber shifts in the N-H stretching and N-H bending modes of pyrrole, as well as in the O-H stretching modes of water and methanol, the 1:1 N-H···O complexes were discerned. The strength of the N-H···O hydrogen bond and the corresponding shift in the N-H stretching vibrational wavenumbers increases in the order pyrrole-water < pyrrole-methanol < pyrrole-dimethyl ether, where a proton is successively replaced by a methyl group. Apart from the 1:1 complexes, higher clusters of 2:1 and 1:2 pyrrole-water and pyrrole-methanol complexes were also generated in N 2 matrix. Atoms in molecules and natural bond orbital analyses were carried out at the MP2/aug-cc-pVDZ level to understand the nature of interaction in the 1:1 pyrrole-water, pyrrole-methanol and pyrrole-dimethyl ether complexes.

Molecular details of the yeast frataxin-Isu1 interaction during mitochondrial Fe-S cluster assembly

PubMed Central

Cook, Jeremy D.; Kondapalli, Kalyan C.; Rawat, Swati; Childs, William C.; Murugesan, Yogapriya; Dancis, Andrew; Stemmler, Timothy L.

2010-01-01

Frataxin, a conserved nuclear encoded mitochondrial protein, plays a direct role in iron-sulfur cluster biosynthesis within the ISC assembly pathway. Humans with frataxin deficiency have Friedreich’s ataxia, a neurodegenerative disorder characterized by mitochondrial iron overload and disruption in Fe-S cluster synthesis. Biochemical and genetic studies have shown frataxin interacts with the iron-sulfur cluster assembly scaffold protein (in yeast, there are two: Isu1 and Isu2), indicating frataxin plays a direct role in cluster assembly, possibly by serving as an iron chaperone n the assembly pathway. Here we provide molecular details of how yeast frataxin (Yfh1) interacts with Isu1 as a structural module to better understand the multiprotein complex assembly that completes Fe-S cluster assembly; this complex also includes the cysteine desulfurase (Nfs1 in yeast) and the accessory protein (Isd11), together in the mitochondria. Thermodynamic binding parameters for protein partner and iron binding were measured for the yeast orthologs using isothermal titration calorimetry (ITC). Nuclear magnetic resonance spectroscopy was used to provide the molecular details to understand how Yfh1 interacts with Isu1. X-ray absorption studies were used to electronically and structurally characterize how iron is transferred to Isu1 and then incorporated into a Fe-S cluster. These results were combined with previously published data to generate a structural model for how the Fe-S cluster protein assembly complex can come together to accomplish Fe-S cluster assembly. PMID:20815377

Molecular Details of the Yeast Frataxin-Isu1 Interaction during Mitochondrial Fe-S Cluster Assembly

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

Cook, J.; Kondapalli, K; Rawat, S

2010-01-01

Frataxin, a conserved nuclear-encoded mitochondrial protein, plays a direct role in iron-sulfur cluster biosynthesis within the ISC assembly pathway. Humans with frataxin deficiency have Friedreich's ataxia, a neurodegenerative disorder characterized by mitochondrial iron overload and disruption in Fe-S cluster synthesis. Biochemical and genetic studies have shown frataxin interacts with the iron-sulfur cluster assembly scaffold protein (in yeast, there are two, Isu1 and Isu2), indicating frataxin plays a direct role in cluster assembly, possibly by serving as an iron chaperone in the assembly pathway. Here we provide molecular details of how yeast frataxin (Yfh1) interacts with Isu1 as a structural modulemore » to improve our understanding of the multiprotein complex assembly that completes Fe-S cluster assembly; this complex also includes the cysteine desulfurase (Nfs1 in yeast) and the accessory protein (Isd11), together in the mitochondria. Thermodynamic binding parameters for protein partner and iron binding were measured for the yeast orthologs using isothermal titration calorimetry. Nuclear magnetic resonance spectroscopy was used to provide the molecular details to understand how Yfh1 interacts with Isu1. X-ray absorption studies were used to electronically and structurally characterize how iron is transferred to Isu1 and then incorporated into an Fe-S cluster. These results were combined with previously published data to generate a structural model for how the Fe-S cluster protein assembly complex can come together to accomplish Fe-S cluster assembly.« less

Molecular details of the yeast frataxin-Isu1 interaction during mitochondrial Fe-S cluster assembly.

PubMed

Cook, Jeremy D; Kondapalli, Kalyan C; Rawat, Swati; Childs, William C; Murugesan, Yogapriya; Dancis, Andrew; Stemmler, Timothy L

2010-10-12

Frataxin, a conserved nuclear-encoded mitochondrial protein, plays a direct role in iron-sulfur cluster biosynthesis within the ISC assembly pathway. Humans with frataxin deficiency have Friedreich's ataxia, a neurodegenerative disorder characterized by mitochondrial iron overload and disruption in Fe-S cluster synthesis. Biochemical and genetic studies have shown frataxin interacts with the iron-sulfur cluster assembly scaffold protein (in yeast, there are two, Isu1 and Isu2), indicating frataxin plays a direct role in cluster assembly, possibly by serving as an iron chaperone in the assembly pathway. Here we provide molecular details of how yeast frataxin (Yfh1) interacts with Isu1 as a structural module to improve our understanding of the multiprotein complex assembly that completes Fe-S cluster assembly; this complex also includes the cysteine desulfurase (Nfs1 in yeast) and the accessory protein (Isd11), together in the mitochondria. Thermodynamic binding parameters for protein partner and iron binding were measured for the yeast orthologs using isothermal titration calorimetry. Nuclear magnetic resonance spectroscopy was used to provide the molecular details to understand how Yfh1 interacts with Isu1. X-ray absorption studies were used to electronically and structurally characterize how iron is transferred to Isu1 and then incorporated into an Fe-S cluster. These results were combined with previously published data to generate a structural model for how the Fe-S cluster protein assembly complex can come together to accomplish Fe-S cluster assembly.

Identifying protein complexes in PPI network using non-cooperative sequential game.

PubMed

Maulik, Ujjwal; Basu, Srinka; Ray, Sumanta

2017-08-21

Identifying protein complexes from protein-protein interaction (PPI) network is an important and challenging task in computational biology as it helps in better understanding of cellular mechanisms in various organisms. In this paper we propose a noncooperative sequential game based model for protein complex detection from PPI network. The key hypothesis is that protein complex formation is driven by mechanism that eventually optimizes the number of interactions within the complex leading to dense subgraph. The hypothesis is drawn from the observed network property named small world. The proposed multi-player game model translates the hypothesis into the game strategies. The Nash equilibrium of the game corresponds to a network partition where each protein either belong to a complex or form a singleton cluster. We further propose an algorithm to find the Nash equilibrium of the sequential game. The exhaustive experiment on synthetic benchmark and real life yeast networks evaluates the structural as well as biological significance of the network partitions.

Helminths and the microbiota: parts of the hygiene hypothesis

PubMed Central

Loke, P’ng; Lim, Yvonne A.L.

2015-01-01

In modern societies, diseases that are driven by dysregulated immune responses are increasing at an alarming pace, such as inflammatory bowel diseases and diabetes. There is an urgent need to understand these epidemiological trends, which are likely to be driven by the changing environment of the last few decades. There are complex interactions between human genetic factors and this changing environment that is leading to the increasing prevalence of metabolic and inflammatory diseases. Alterations to human gut bacterial communities (the microbiota) and lowered prevalence of helminth infections are potential environmental factors contributing to immune dysregulation. Helminths have co-evolved with the gut microbiota and their mammalian hosts. This three-way interaction is beginning to be characterized and the knowledge gained may enable the design of new therapeutic strategies to treat metabolic and inflammatory diseases. However, these complex interactions need to be carefully investigated in the context of host genetic backgrounds in order to identify optimal treatment strategies. The complex nature of these interactions raises the possibility that only with highly personalized treatment, with knowledge of individual genetic and microbiota communities, will therapeutic interventions be successful for a majority of the individuals suffering from these complex diseases of immune dysregulation. PMID:25869420

Weak conservation of structural features in the interfaces of homologous transient protein–protein complexes

PubMed Central

Sudha, Govindarajan; Singh, Prashant; Swapna, Lakshmipuram S; Srinivasan, Narayanaswamy

2015-01-01

Residue types at the interface of protein–protein complexes (PPCs) are known to be reasonably well conserved. However, we show, using a dataset of known 3-D structures of homologous transient PPCs, that the 3-D location of interfacial residues and their interaction patterns are only moderately and poorly conserved, respectively. Another surprising observation is that a residue at the interface that is conserved is not necessarily in the interface in the homolog. Such differences in homologous complexes are manifested by substitution of the residues that are spatially proximal to the conserved residue and structural differences at the interfaces as well as differences in spatial orientations of the interacting proteins. Conservation of interface location and the interaction pattern at the core of the interfaces is higher than at the periphery of the interface patch. Extents of variability of various structural features reported here for homologous transient PPCs are higher than the variation in homologous permanent homomers. Our findings suggest that straightforward extrapolation of interfacial nature and inter-residue interaction patterns from template to target could lead to serious errors in the modeled complex structure. Understanding the evolution of interfaces provides insights to improve comparative modeling of PPC structures. PMID:26311309

Helminths and the microbiota: parts of the hygiene hypothesis.

PubMed

Loke, P; Lim, Y A L

2015-06-01

In modern societies, diseases that are driven by dysregulated immune responses are increasing at an alarming pace, such as inflammatory bowel diseases and diabetes. There is an urgent need to understand these epidemiological trends, which are likely to be driven by the changing environment of the last few decades. There are complex interactions between human genetic factors and this changing environment that is leading to the increasing prevalence of metabolic and inflammatory diseases. Alterations to human gut bacterial communities (the microbiota) and lowered prevalence of helminth infections are potential environmental factors contributing to immune dysregulation. Helminths have co-evolved with the gut microbiota and their mammalian hosts. This three-way interaction is beginning to be characterized, and the knowledge gained may enable the design of new therapeutic strategies to treat metabolic and inflammatory diseases. However, these complex interactions need to be carefully investigated in the context of host genetic backgrounds to identify optimal treatment strategies. The complex nature of these interactions raises the possibility that only with highly personalized treatment, with knowledge of individual genetic and microbiota communities, will therapeutic interventions be successful for a majority of the individuals suffering from these complex diseases of immune dysregulation. © 2015 John Wiley & Sons Ltd.

Toy models and stylized realities

NASA Astrophysics Data System (ADS)

Marsili, M.

2007-01-01

I discuss the role of toy models as theoretical tools for understanding complex systems of interacting agents. I review some concrete examples, in order to illustrate how this approach is able to capture, though in an admittedly stylized way, the interactions and non-linearities which are responsible for the rich phenomenology observed in reality. This allows one to interpret the system's behavior in terms of phase transitions and critical phenomena.

Interactive modelling with stakeholders in two cases in flood management

NASA Astrophysics Data System (ADS)

Leskens, Johannes; Brugnach, Marcela

2013-04-01

New policies on flood management called Multi-Level Safety (MLS), demand for an integral and collaborative approach. The goal of MLS is to minimize flood risks by a coherent package of protection measures, crisis management and flood resilience measures. To achieve this, various stakeholders, such as water boards, municipalities and provinces, have to collaborate in composing these measures. Besides the many advances this integral and collaborative approach gives, the decision-making environment becomes also more complex. Participants have to consider more criteria than they used to do and have to take a wide network of participants into account, all with specific perspectives, cultures and preferences. In response, sophisticated models are developed to support decision-makers in grasping this complexity. These models provide predictions of flood events and offer the opportunity to test the effectiveness of various measures under different criteria. Recent model advances in computation speed and model flexibility allow stakeholders to directly interact with a hydrological hydraulic model during meetings. Besides a better understanding of the decision content, these interactive models are supposed to support the incorporation of stakeholder knowledge in modelling and to support mutual understanding of different perspectives of stakeholders To explore the support of interactive modelling in integral and collaborate policies, such as MLS, we tested a prototype of an interactive flood model (3Di) with respect to a conventional model (Sobek) in two cases. The two cases included the designing of flood protection measures in Amsterdam and a flood event exercise in Delft. These case studies yielded two main results. First, we observed that in the exploration phase of a decision-making process, stakeholders participated actively in interactive modelling sessions. This increased the technical understanding of complex problems and the insight in the effectiveness of various integral measures. Second, when measures became more concrete, the model played a minor role, as stakeholders were still bounded to goals, responsibilities and budgets of their own organization. Model results in this phase are mainly used in a political way to maximize the goals of particular organizations.

Graphical Understanding of Simple Feedback Systems.

ERIC Educational Resources Information Center

Janvier, Claude; Garancon, Maurice

1989-01-01

Shows that graphs can reveal much about feedback systems that formula conceal, especially as microcomputers can provide complex graphs presented as animations and allow students to interact easily with them. Describes feedback systems, evolution of the system, and phase diagram. (YP)

Charge-transfer interaction of drug quinidine with quinol, picric acid and DDQ: Spectroscopic characterization and biological activity studies towards understanding the drug-receptor mechanism.

PubMed

Eldaroti, Hala H; Gadir, Suad A; Refat, Moamen S; Adam, Abdel Majid A

2014-04-01

Investigation of charge-transfer (CT) complexes of drugs has been recognized as an important phenomenon in understanding of the drug-receptor binding mechanism. Structural, thermal, morphological and biological behavior of CT complexes formed between drug quinidine (Qui) as a donor and quinol (QL), picric acid (PA) or dichlorodicyanobenzoquinone (DDQ) as acceptors were reported. The newly synthesized CT complexes have been spectroscopically characterized via elemental analysis; infrared (IR), Raman, 1 H NMR and electronic absorption spectroscopy; powder X-ray diffraction (PXRD); thermogravimetric (TG) analysis and scanning electron microscopy (SEM). It was found that the obtained complexes are nanoscale, semi-crystalline particles, thermally stable and spontaneous. The molecular composition of the obtained complexes was determined using spectrophotometric titration method and was found to be 1:1 ratios (donor:acceptor). Finally, the biological activities of the obtained CT complexes were tested for their antibacterial activities. The results obtained herein are satisfactory for estimation of drug Qui in the pharmaceutical form.

Two-dimensional blue native/SDS-PAGE analysis of whole cell lysate protein complexes of rice in response to salt stress.

PubMed

Hashemi, Amenehsadat; Gharechahi, Javad; Nematzadeh, Ghorbanali; Shekari, Faezeh; Hosseini, Seyed Abdollah; Salekdeh, Ghasem Hosseini

2016-08-01

To understand the biology of a plant in response to stress, insight into protein-protein interactions, which almost define cell behavior, is thought to be crucial. Here, we provide a comparative complexomics analysis of leaf whole cell lysate of two rice genotypes with contrasting responses to salt using two-dimensional blue native/SDS-PAGE (2D-BN/SDS-PAGE). We aimed to identify changes in subunit composition and stoichiometry of protein complexes elicited by salt. Using mild detergent for protein complex solubilization, we were able to identify 9 protein assemblies as hetero-oligomeric and 30 as homo-oligomeric complexes. A total of 20 proteins were identified as monomers in the 2D-BN/SDS-PAGE gels. In addition to identifying known protein complexes that confirm the technical validity of our analysis, we were also able to discover novel protein-protein interactions. Interestingly, an interaction was detected for glycolytic enzymes enolase (ENO1) and triosephosphate isomerase (TPI) and also for a chlorophyll a-b binding protein and RuBisCo small subunit. To show changes in subunit composition and stoichiometry of protein assemblies during salt stress, the differential abundance of interacting proteins was compared between salt-treated and control plants. A detailed exploration of some of the protein complexes provided novel insight into the function, composition, stoichiometry and dynamics of known and previously uncharacterized protein complexes in response to salt stress. Copyright © 2016 Elsevier GmbH. All rights reserved.

Dendrimer Interactions with Lipid Bilayer: Comparison of Force Field and Effect of Implicit vs Explicit Solvation.

PubMed

Kanchi, Subbarao; Gosika, Mounika; Ayappa, K G; Maiti, Prabal K

2018-06-13

The understanding of dendrimer interactions with cell membranes has great importance in drug/gene delivery based therapeutics. Although molecular simulations have been used to understand the nature of dendrimer interactions with lipid membranes, its dependency on available force field parameters is poorly understood. In this study, we have carried out fully atomistic molecular dynamics (MD) simulations of a protonated G3 poly(amido amine) (PAMAM) dendrimer-dimyristoylphosphatidylcholine (DMPC) lipid bilayer complex using three different force fields (FFs) namely, CHARMM, GAFF, and GROMOS in the presence of explicit water to understand the structure of the lipid-dendrimer complex and nature of their interaction. CHARMM and GAFF dendrimers initially in contact with the lipid head groups were found to move away from the lipid bilayer during the course of simulation; however, the dendrimer remained strongly bound to the lipid head groups with the GROMOS FF. Potential of the mean force (PMF) computations of the dendrimer along the bilayer normal showed a repulsive barrier (∼20 kcal/mol) between dendrimer and lipid bilayer in the case of CHARMM and GAFF force fields. In contrast, an attractive interaction (∼40 kcal/mol) is obtained with the GROMOS force field, consistent with experimental observations of membrane binding observed with lower generation G3 PAMAM dendrimers. This difference with the GROMOS dendrimer is attributed to the strong dendrimer-lipid interaction and lowered surface hydration of the dendrimer. Assessing the role of solvent, we find that the CHARMM and GAFF dendrimers strongly bind to the lipid bilayer with an implicit solvent (Generalized Born) model, whereas binding is not observed with explicit water (TIP3P). The opposing nature of dendrimer-membrane interactions in the presence of explicit and implicit solvents demonstrates that hydration effects play an important role in modulating the dendrimer-lipid interaction warranting a case for refinement of the existing dendrimer/lipid force fields.

PAMPs, PRRs, effectors and R-genes associated with citrus-pathogen interactions.

PubMed

Dalio, Ronaldo J D; Magalhães, Diogo M; Rodrigues, Carolina M; Arena, Gabriella D; Oliveira, Tiago S; Souza-Neto, Reinaldo R; Picchi, Simone C; Martins, Paula M M; Santos, Paulo J C; Maximo, Heros J; Pacheco, Inaiara S; De Souza, Alessandra A; Machado, Marcos A

2017-03-01

Recent application of molecular-based technologies has considerably advanced our understanding of complex processes in plant-pathogen interactions and their key components such as PAMPs, PRRs, effectors and R-genes. To develop novel control strategies for disease prevention in citrus, it is essential to expand and consolidate our knowledge of the molecular interaction of citrus plants with their pathogens. This review provides an overview of our understanding of citrus plant immunity, focusing on the molecular mechanisms involved in the interactions with viruses, bacteria, fungi, oomycetes and vectors related to the following diseases: tristeza, psorosis, citrus variegated chlorosis, citrus canker, huanglongbing, brown spot, post-bloom, anthracnose, gummosis and citrus root rot. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Discrete structural features among interface residue-level classes.

PubMed

Sowmya, Gopichandran; Ranganathan, Shoba

2015-01-01

Protein-protein interaction (PPI) is essential for molecular functions in biological cells. Investigation on protein interfaces of known complexes is an important step towards deciphering the driving forces of PPIs. Each PPI complex is specific, sensitive and selective to binding. Therefore, we have estimated the relative difference in percentage of polar residues between surface and the interface for each complex in a non-redundant heterodimer dataset of 278 complexes to understand the predominant forces driving binding. Our analysis showed ~60% of protein complexes with surface polarity greater than interface polarity (designated as class A). However, a considerable number of complexes (~40%) have interface polarity greater than surface polarity, (designated as class B), with a significantly different p-value of 1.66E-45 from class A. Comprehensive analyses of protein complexes show that interface features such as interface area, interface polarity abundance, solvation free energy gain upon interface formation, binding energy and the percentage of interface charged residue abundance distinguish among class A and class B complexes, while electrostatic visualization maps also help differentiate interface classes among complexes. Class A complexes are classical with abundant non-polar interactions at the interface; however class B complexes have abundant polar interactions at the interface, similar to protein surface characteristics. Five physicochemical interface features analyzed from the protein heterodimer dataset are discriminatory among the interface residue-level classes. These novel observations find application in developing residue-level models for protein-protein binding prediction, protein-protein docking studies and interface inhibitor design as drugs.

Discrete structural features among interface residue-level classes

PubMed Central

2015-01-01

Background Protein-protein interaction (PPI) is essential for molecular functions in biological cells. Investigation on protein interfaces of known complexes is an important step towards deciphering the driving forces of PPIs. Each PPI complex is specific, sensitive and selective to binding. Therefore, we have estimated the relative difference in percentage of polar residues between surface and the interface for each complex in a non-redundant heterodimer dataset of 278 complexes to understand the predominant forces driving binding. Results Our analysis showed ~60% of protein complexes with surface polarity greater than interface polarity (designated as class A). However, a considerable number of complexes (~40%) have interface polarity greater than surface polarity, (designated as class B), with a significantly different p-value of 1.66E-45 from class A. Comprehensive analyses of protein complexes show that interface features such as interface area, interface polarity abundance, solvation free energy gain upon interface formation, binding energy and the percentage of interface charged residue abundance distinguish among class A and class B complexes, while electrostatic visualization maps also help differentiate interface classes among complexes. Conclusions Class A complexes are classical with abundant non-polar interactions at the interface; however class B complexes have abundant polar interactions at the interface, similar to protein surface characteristics. Five physicochemical interface features analyzed from the protein heterodimer dataset are discriminatory among the interface residue-level classes. These novel observations find application in developing residue-level models for protein-protein binding prediction, protein-protein docking studies and interface inhibitor design as drugs. PMID:26679043

Taxonomy for complexity theory in the context of maternity care.

PubMed

Nieuwenhuijze, Marianne; Downe, Soo; Gottfreðsdóttir, Helga; Rijnders, Marlies; du Preez, Antoinette; Vaz Rebelo, Piedade

2015-09-01

The linear focus of 'normal science' is unable to adequately take account of the complex interactions that direct health care systems. There is a turn towards complexity theory as a more appropriate framework for understanding system behaviour. However, a comprehensive taxonomy for complexity theory in the context of health care is lacking. This paper aims to build a taxonomy based on the key complexity theory components that have been used in publications on complexity theory and health care, and to explore their explanatory power for health care system behaviour, specifically for maternity care. A search strategy was devised in PubMed and 31 papers were identified as relevant for the taxonomy. The final taxonomy for complexity theory included and defined 11 components. The use of waterbirth and the impact of the Term Breech trial showed that each of the components of our taxonomy has utility in helping to understand how these techniques became widely adopted. It is not just the components themselves that characterise a complex system but also the dynamics between them. Copyright © 2015 Elsevier Ltd. All rights reserved.

Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens.

PubMed

Pan, Joshua; Meyers, Robin M; Michel, Brittany C; Mashtalir, Nazar; Sizemore, Ann E; Wells, Jonathan N; Cassel, Seth H; Vazquez, Francisca; Weir, Barbara A; Hahn, William C; Marsh, Joseph A; Tsherniak, Aviad; Kadoch, Cigall

2018-05-23

Protein complexes are assemblies of subunits that have co-evolved to execute one or many coordinated functions in the cellular environment. Functional annotation of mammalian protein complexes is critical to understanding biological processes, as well as disease mechanisms. Here, we used genetic co-essentiality derived from genome-scale RNAi- and CRISPR-Cas9-based fitness screens performed across hundreds of human cancer cell lines to assign measures of functional similarity. From these measures, we systematically built and characterized functional similarity networks that recapitulate known structural and functional features of well-studied protein complexes and resolve novel functional modules within complexes lacking structural resolution, such as the mammalian SWI/SNF complex. Finally, by integrating functional networks with large protein-protein interaction networks, we discovered novel protein complexes involving recently evolved genes of unknown function. Taken together, these findings demonstrate the utility of genetic perturbation screens alone, and in combination with large-scale biophysical data, to enhance our understanding of mammalian protein complexes in normal and disease states. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Toward a more complete understanding of noncovalent interactions involving aromatic rings.

PubMed

Wheeler, Steven E; Bloom, Jacob W G

2014-08-14

Noncovalent interactions involving aromatic rings, which include π-stacking interactions, anion-π interactions, and XH-π interactions, among others, are ubiquitous in chemical and biochemical systems. Despite dramatic advances in our understanding of these interactions over the past decade, many aspects of these noncovalent interactions have only recently been uncovered, with many questions remaining. We summarize our computational studies aimed at understanding the impact of substituents and heteroatoms on these noncovalent interactions. In particular, we discuss our local, direct interaction model of substituent effects in π-stacking interactions. In this model, substituent effects are dominated by electrostatic interactions of the local dipoles associated with the substituents and the electric field of the other ring. The implications of the local nature of substituent effects on π-stacking interactions in larger systems are discussed, with examples given for complexes with carbon nanotubes and a small graphene model, as well as model stacked discotic systems. We also discuss related issues involving the interpretation of electrostatic potential (ESP) maps. Although ESP maps are widely used in discussions of noncovalent interactions, they are often misinterpreted. Next, we provide an alternative explanation for the origin of anion-π interactions involving substituted benzenes and N-heterocycles, and show that these interactions are well-described by simple models based solely on charge-dipole interactions. Finally, we summarize our recent work on the physical nature of substituent effects in XH-π interactions. Together, these results paint a more complete picture of noncovalent interactions involving aromatic rings and provide a firm conceptual foundation for the rational exploitation of these interactions in a myriad of chemical contexts.

The architecture of the DNA replication origin recognition complex in Saccharomyces cerevisiae

PubMed Central

Chen, Zhiqiang; Speck, Christian; Wendel, Patricia; Tang, Chunyan; Stillman, Bruce; Li, Huilin

2008-01-01

The origin recognition complex (ORC) is conserved in all eukaryotes. The six proteins of the Saccharomyces cerevisiae ORC that form a stable complex bind to origins of DNA replication and recruit prereplicative complex (pre-RC) proteins, one of which is Cdc6. To further understand the function of ORC we recently determined by single-particle reconstruction of electron micrographs a low-resolution, 3D structure of S. cerevisiae ORC and the ORC–Cdc6 complex. In this article, the spatial arrangement of the ORC subunits within the ORC structure is described. In one approach, a maltose binding protein (MBP) was systematically fused to the N or the C termini of the five largest ORC subunits, one subunit at a time, generating 10 MBP-fused ORCs, and the MBP density was localized in the averaged, 2D EM images of the MBP-fused ORC particles. Determining the Orc1–5 structure and comparing it with the native ORC structure localized the Orc6 subunit near Orc2 and Orc3. Finally, subunit–subunit interactions were determined by immunoprecipitation of ORC subunits synthesized in vitro. Based on the derived ORC architecture and existing structures of archaeal Orc1–DNA structures, we propose a model for ORC and suggest how ORC interacts with origin DNA and Cdc6. The studies provide a basis for understanding the overall structure of the pre-RC. PMID:18647841

Beyond the G-spot: clitourethrovaginal complex anatomy in female orgasm.

PubMed

Jannini, Emmanuele A; Buisson, Odile; Rubio-Casillas, Alberto

2014-09-01

The search for the legendary, highly erogenous vaginal region, the Gräfenberg spot (G-spot), has produced important data, substantially improving understanding of the complex anatomy and physiology of sexual responses in women. Modern imaging techniques have enabled visualization of dynamic interactions of female genitals during self-sexual stimulation or coitus. Although no single structure consistent with a distinct G-spot has been identified, the vagina is not a passive organ but a highly dynamic structure with an active role in sexual arousal and intercourse. The anatomical relationships and dynamic interactions between the clitoris, urethra, and anterior vaginal wall have led to the concept of a clitourethrovaginal (CUV) complex, defining a variable, multifaceted morphofunctional area that, when properly stimulated during penetration, could induce orgasmic responses. Knowledge of the anatomy and physiology of the CUV complex might help to avoid damage to its neural, muscular, and vascular components during urological and gynaecological surgical procedures.

Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium

PubMed Central

Hill, David R; Huang, Sha; Nagy, Melinda S; Yadagiri, Veda K; Fields, Courtney; Mukherjee, Dishari; Bons, Brooke; Dedhia, Priya H; Chin, Alana M; Tsai, Yu-Hwai; Thodla, Shrikar; Schmidt, Thomas M; Walk, Seth

2017-01-01

The human gastrointestinal tract is immature at birth, yet must adapt to dramatic changes such as oral nutrition and microbial colonization. The confluence of these factors can lead to severe inflammatory disease in premature infants; however, investigating complex environment-host interactions is difficult due to limited access to immature human tissue. Here, we demonstrate that the epithelium of human pluripotent stem-cell-derived human intestinal organoids is globally similar to the immature human epithelium and we utilize HIOs to investigate complex host-microbe interactions in this naive epithelium. Our findings demonstrate that the immature epithelium is intrinsically capable of establishing a stable host-microbe symbiosis. Microbial colonization leads to complex contact and hypoxia driven responses resulting in increased antimicrobial peptide production, maturation of the mucus layer, and improved barrier function. These studies lay the groundwork for an improved mechanistic understanding of how colonization influences development of the immature human intestine. PMID:29110754

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

Borreguero, Jose M.; Pincus, Philip A.; Sumpter, Bobby G.

Structure–property relationships of ionic block copolymer (BCP) surfactant complexes are critical toward the progress of favorable engineering design of efficient charge-transport materials. In this paper, molecular dynamics simulations are used to understand the dynamics of charged-neutral BCP and surfactant complexes. The dynamics are examined for two different systems: charged-neutral double-hydrophilic and hydrophobic–hydrophilic block copolymers with oppositely charged surfactant moieties. The dynamics of the surfactant head, tails, and charges are studied for five different BCP volume fractions. We observe that the dynamics of the different species solely depend on the balance between electrostatic and entropic interactions between the charged species andmore » the neutral monomers. The favorable hydrophobic–hydrophobic interactions and the unfavorable hydrophobic–hydrophilic interactions determine the mobilities of the monomers. The dynamical properties of the charge species influence complex formation. Structural relaxations exhibit length-scale dependent behavior, with slower relaxation at the radius of gyration length-scale and faster relaxation at the segmental length-scale, consistent with previous results. The dynamical analysis correlates ion-exchange kinetics to the self-assembly behavior of the complexes.« less

Experimental and Theoretical Approaches for the Surface Interaction between Copper and Activated Sludge Microorganisms at Molecular Scale

NASA Astrophysics Data System (ADS)

Luo, Hong-Wei; Chen, Jie-Jie; Sheng, Guo-Ping; Su, Ji-Hu; Wei, Shi-Qiang; Yu, Han-Qing

2014-11-01

Interactions between metals and activated sludge microorganisms substantially affect the speciation, immobilization, transport, and bioavailability of trace heavy metals in biological wastewater treatment plants. In this study, the interaction of Cu(II), a typical heavy metal, onto activated sludge microorganisms was studied in-depth using a multi-technique approach. The complexing structure of Cu(II) on microbial surface was revealed by X-ray absorption fine structure (XAFS) and electron paramagnetic resonance (EPR) analysis. EPR spectra indicated that Cu(II) was held in inner-sphere surface complexes of octahedral coordination with tetragonal distortion of axial elongation. XAFS analysis further suggested that the surface complexation between Cu(II) and microbial cells was the distorted inner-sphere coordinated octahedra containing four short equatorial bonds and two elongated axial bonds. To further validate the results obtained from the XAFS and EPR analysis, density functional theory calculations were carried out to explore the structural geometry of the Cu complexes. These results are useful to better understand the speciation, immobilization, transport, and bioavailability of metals in biological wastewater treatment plants.

Spatial Characterization of Riparian Buffer Effects on Sediment Loads from Watershed Systems

EPA Science Inventory

Understanding all watershed systems and their interactions is a complex, but critical, undertaking when developing practices designed to reduce topsoil loss and chemical/nutrient transport from agricultural fields. The presence of riparian buffer vegetation in agricultural lands...

MIMO: an efficient tool for molecular interaction maps overlap

PubMed Central

2013-01-01

Background Molecular pathways represent an ensemble of interactions occurring among molecules within the cell and between cells. The identification of similarities between molecular pathways across organisms and functions has a critical role in understanding complex biological processes. For the inference of such novel information, the comparison of molecular pathways requires to account for imperfect matches (flexibility) and to efficiently handle complex network topologies. To date, these characteristics are only partially available in tools designed to compare molecular interaction maps. Results Our approach MIMO (Molecular Interaction Maps Overlap) addresses the first problem by allowing the introduction of gaps and mismatches between query and template pathways and permits -when necessary- supervised queries incorporating a priori biological information. It then addresses the second issue by relying directly on the rich graph topology described in the Systems Biology Markup Language (SBML) standard, and uses multidigraphs to efficiently handle multiple queries on biological graph databases. The algorithm has been here successfully used to highlight the contact point between various human pathways in the Reactome database. Conclusions MIMO offers a flexible and efficient graph-matching tool for comparing complex biological pathways. PMID:23672344

Synthetic microbial ecology and the dynamic interplay between microbial genotypes.

PubMed

Dolinšek, Jan; Goldschmidt, Felix; Johnson, David R

2016-11-01

Assemblages of microbial genotypes growing together can display surprisingly complex and unexpected dynamics and result in community-level functions and behaviors that are not readily expected from analyzing each genotype in isolation. This complexity has, at least in part, inspired a discipline of synthetic microbial ecology. Synthetic microbial ecology focuses on designing, building and analyzing the dynamic behavior of ‘ecological circuits’ (i.e. a set of interacting microbial genotypes) and understanding how community-level properties emerge as a consequence of those interactions. In this review, we discuss typical objectives of synthetic microbial ecology and the main advantages and rationales of using synthetic microbial assemblages. We then summarize recent findings of current synthetic microbial ecology investigations. In particular, we focus on the causes and consequences of the interplay between different microbial genotypes and illustrate how simple interactions can create complex dynamics and promote unexpected community-level properties. We finally propose that distinguishing between active and passive interactions and accounting for the pervasiveness of competition can improve existing frameworks for designing and predicting the dynamics of microbial assemblages.

Co-operative intra-protein structural response due to protein-protein complexation revealed through thermodynamic quantification: study of MDM2-p53 binding

NASA Astrophysics Data System (ADS)

Samanta, Sudipta; Mukherjee, Sanchita

2017-10-01

The p53 protein activation protects the organism from propagation of cells with damaged DNA having oncogenic mutations. In normal cells, activity of p53 is controlled by interaction with MDM2. The well understood p53-MDM2 interaction facilitates design of ligands that could potentially disrupt or prevent the complexation owing to its emergence as an important objective for cancer therapy. However, thermodynamic quantification of the p53-peptide induced structural changes of the MDM2-protein remains an area to be explored. This study attempts to understand the conformational free energy and entropy costs due to this complex formation from the histograms of dihedral angles generated from molecular dynamics simulations. Residue-specific quantification illustrates that, hydrophobic residues of the protein contribute maximum to the conformational thermodynamic changes. Thermodynamic quantification of structural changes of the protein unfold the fact that, p53 binding provides a source of inter-element cooperativity among the protein secondary structural elements, where the highest affected structural elements (α2 and α4) found at the binding site of the protein affects faraway structural elements (β1 and Loop1) of the protein. The communication perhaps involves water mediated hydrogen bonded network formation. Further, we infer that in inhibitory F19A mutation of P53, though Phe19 is important in the recognition process, it has less prominent contribution in the stability of the complex. Collectively, this study provides vivid microscopic understanding of the interaction within the protein complex along with exploring mutation sites, which will contribute further to engineer the protein function and binding affinity.

Interpreting three-dimensional structures from two-dimensional images: a web-based interactive 3D teaching model of surgical liver anatomy

PubMed Central

Crossingham, Jodi L; Jenkinson, Jodie; Woolridge, Nick; Gallinger, Steven; Tait, Gordon A; Moulton, Carol-Anne E

2009-01-01

Background: Given the increasing number of indications for liver surgery and the growing complexity of operations, many trainees in surgical, imaging and related subspecialties require a good working knowledge of the complex intrahepatic anatomy. Computed tomography (CT), the most commonly used liver imaging modality, enhances our understanding of liver anatomy, but comprises a two-dimensional (2D) representation of a complex 3D organ. It is challenging for trainees to acquire the necessary skills for converting these 2D images into 3D mental reconstructions because learning opportunities are limited and internal hepatic anatomy is complicated, asymmetrical and variable. We have created a website that uses interactive 3D models of the liver to assist trainees in understanding the complex spatial anatomy of the liver and to help them create a 3D mental interpretation of this anatomy when viewing CT scans. Methods: Computed tomography scans were imported into DICOM imaging software (OsiriX™) to obtain 3D surface renderings of the liver and its internal structures. Using these 3D renderings as a reference, 3D models of the liver surface and the intrahepatic structures, portal veins, hepatic veins, hepatic arteries and the biliary system were created using 3D modelling software (Cinema 4D™). Results: Using current best practices for creating multimedia tools, a unique, freely available, online learning resource has been developed, entitled Visual Interactive Resource for Teaching, Understanding And Learning Liver Anatomy (VIRTUAL Liver) (http://pie.med.utoronto.ca/VLiver). This website uses interactive 3D models to provide trainees with a constructive resource for learning common liver anatomy and liver segmentation, and facilitates the development of the skills required to mentally reconstruct a 3D version of this anatomy from 2D CT scans. Discussion: Although the intended audience for VIRTUAL Liver consists of residents in various medical and surgical specialties, the website will also be useful for other health care professionals (i.e. radiologists, nurses, hepatologists, radiation oncologists, family doctors) and educators because it provides a comprehensive resource for teaching liver anatomy. PMID:19816618

Study on the interaction of a copper(II) complex containing the artificial sweetener aspartame with human serum albumin.

PubMed

Shahabadi, Nahid; Khodaei, Mohammad Mehdi; Kashanian, Soheila; Kheirdoosh, Fahimeh; Filli, Soraya Moradi

2014-05-01

A copper(II) complex containing aspartame (APM) as ligand, Cu(APM)2Cl2·2H2O, was synthesized and characterized. In vitro binding interaction of this complex with human serum albumin (HSA) was studied at physiological pH. Binding studies of this complex with HSA are useful for understanding the Cu(APM)2Cl2·2H2O-HSA interaction mechanism and providing guidance for the application and design of new and more efficient artificial sweeteners drive. The interaction was investigated by spectrophotometric, spectrofluorometric, competition experiment and circular dichroism. Hyperchromicity observed in UV absorption band of Cu(APM)2Cl2·2H2O. A strong fluorescence quenching reaction of HSA to Cu(APM)2Cl2·2H2O was observed and the binding constant (Kf) and corresponding numbers of binding sites (n) were calculated at different temperatures. Thermodynamic parameters, enthalpy change (∆H) and entropy change (∆S) were calculated to be -458.67 kJ mol(-1) and -1,339 J mol(-1 )K(-1) respectively. According to the van't Hoff equation, the reaction is predominantly enthalpically driven. In conformity with experimental results, we suggest that Cu(APM)2Cl2·2H2O interacts with HSA. In comparison with previous study, it is found that the Cu(II) complex binds stronger than aspartame.

Understanding a Complex World: Why an Emphasis on Empathy Could Better Enable Army Leaders to Win

DTIC Science & Technology

2016-06-10

complexity and speed of human interactions. Through the analysis of case studies involving General Stanley McChrystal and Colonel Michael Steele , this...Future; Win; Dilemma; Leadership; McChrystal, Stanley; Steele , Michael 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF...Stanley McChrystal and Colonel Michael Steele , this thesis describes how each individual’s empathetic mindset resulted in both favorable and

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

Deng, Ye; Zhang, Ping; Qin, Yujia

When trying to discern network interactions among different species/populations in microbial communities interests have been evoked in recent years, but little information is available about temporal dynamics of microbial network interactions in response to environmental perturbations. We modified the random matrix theory-based network approach to discern network succession in groundwater microbial communities in response to emulsified vegetable oil (EVO) amendment for uranium bioremediation. Groundwater microbial communities from one control and seven monitor wells were analysed with a functional gene array (GeoChip 3.0), and functional molecular ecological networks (fMENs) at different time points were reconstructed. Our results showed that the networkmore » interactions were dramatically altered by EVO amendment. Dynamic and resilient succession was evident: fairly simple at the initial stage (Day 0), increasingly complex at the middle period (Days 4, 17, 31), most complex at Day 80, and then decreasingly complex at a later stage (140–269 days). Unlike previous studies in other habitats, negative interactions predominated in a time-series fMEN, suggesting strong competition among different microbial species in the groundwater systems after EVO injection. In particular, several keystone sulfate-reducing bacteria showed strong negative interactions with their network neighbours. These results provide mechanistic understanding of the decreased phylogenetic diversity during environmental perturbations.« less

Structural Characterisation of Fenchone and its Complexes with Ethanol by Broadband Rotational Spectroscopy

NASA Astrophysics Data System (ADS)

Loru, Donatella; Sanz, M. Eugenia

2016-06-01

Although significant advances in understanding the human olfactory system have taken place over the last two decades, detailed information on how the interactions between odorants and olfactory receptors occur at the molecular level is still lacking. To achieve a better understanding on the molecular mechanisms involved in olfaction, we are investigating several odorants and their interactions with mimics of amino acid residues in olfactory receptors. We present here the structural characterisation of fenchone (C10H16O) and its complexes with ethanol (to mimic the side chain of serine) using a 2-8 GHz chirped-pulse Fourier transform microwave spectrometer built at King's College London. The rotational spectrum of the parent species and all the 13C and 18O isotopologues of fenchone was observed, and from the experimental rotational constants the substitution (r0) and effective (rs) structures of fenchone were determined. The rotational spectrum of fenchone-ethanol was observed by adding ethanol to the carrier gas and passing the mixture through a receptacle with fenchone. Several 1:1 complexes of fenchone-ethanol have been identified in the rotational spectrum. In all the complexes the ethanol molecule binds to the carbonyl group through an O-H· · · O hydrogen bond.

Genome-centric resolution of microbial diversity, metabolism and interactions in anaerobic digestion.

PubMed

Vanwonterghem, Inka; Jensen, Paul D; Rabaey, Korneel; Tyson, Gene W

2016-09-01

Our understanding of the complex interconnected processes performed by microbial communities is hindered by our inability to culture the vast majority of microorganisms. Metagenomics provides a way to bypass this cultivation bottleneck and recent advances in this field now allow us to recover a growing number of genomes representing previously uncultured populations from increasingly complex environments. In this study, a temporal genome-centric metagenomic analysis was performed of lab-scale anaerobic digesters that host complex microbial communities fulfilling a series of interlinked metabolic processes to enable the conversion of cellulose to methane. In total, 101 population genomes that were moderate to near-complete were recovered based primarily on differential coverage binning. These populations span 19 phyla, represent mostly novel species and expand the genomic coverage of several rare phyla. Classification into functional guilds based on their metabolic potential revealed metabolic networks with a high level of functional redundancy as well as niche specialization, and allowed us to identify potential roles such as hydrolytic specialists for several rare, uncultured populations. Genome-centric analyses of complex microbial communities across diverse environments provide the key to understanding the phylogenetic and metabolic diversity of these interactive communities. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

The Role of Shape Complementarity in the Protein-Protein Interactions

PubMed Central

Li, Ye; Zhang, Xianren; Cao, Dapeng

2013-01-01

We use a dissipative particle dynamic simulation to investigate the effects of shape complementarity on the protein-protein interactions. By monitoring different kinds of protein shape-complementarity modes, we gave a clear mechanism to reveal the role of the shape complementarity in the protein-protein interactions, i.e., when the two proteins with shape complementarity approach each other, the conformation of lipid chains between two proteins would be restricted significantly. The lipid molecules tend to leave the gap formed by two proteins to maximize the configuration entropy, and therefore yield an effective entropy-induced protein-protein attraction, which enhances the protein aggregation. In short, this work provides an insight into understanding the importance of the shape complementarity in the protein-protein interactions especially for protein aggregation and antibody–antigen complexes. Definitely, the shape complementarity is the third key factor affecting protein aggregation and complex, besides the electrostatic-complementarity and hydrophobic complementarity. PMID:24253561

The Role of Shape Complementarity in the Protein-Protein Interactions

NASA Astrophysics Data System (ADS)

Li, Ye; Zhang, Xianren; Cao, Dapeng

2013-11-01

We use a dissipative particle dynamic simulation to investigate the effects of shape complementarity on the protein-protein interactions. By monitoring different kinds of protein shape-complementarity modes, we gave a clear mechanism to reveal the role of the shape complementarity in the protein-protein interactions, i.e., when the two proteins with shape complementarity approach each other, the conformation of lipid chains between two proteins would be restricted significantly. The lipid molecules tend to leave the gap formed by two proteins to maximize the configuration entropy, and therefore yield an effective entropy-induced protein-protein attraction, which enhances the protein aggregation. In short, this work provides an insight into understanding the importance of the shape complementarity in the protein-protein interactions especially for protein aggregation and antibody-antigen complexes. Definitely, the shape complementarity is the third key factor affecting protein aggregation and complex, besides the electrostatic-complementarity and hydrophobic complementarity.

Nanoscale Structure and Interaction of Compact Assemblies of Carbon Nano-Materials

NASA Astrophysics Data System (ADS)

Timsina, Raju; Qiu, Xiangyun

Carbon-based nano-materials (CNM) are a diverse family of multi-functional materials under research and development world wide. Our work is further motivated by the predictive power of the physical understanding of the underlying structure-interaction-function relationships. Here we present results form recent studies of the condensed phases of several model CNMs in complexation with biologically derived molecules. Specifically, we employ X-ray diffraction (XRD) to determine nanoscale structures and use the osmotic stress method to quantify their interactions. The systems under investigation are dsDNA-dispersed carbon nanotubes (dsDNA-CNT), bile-salt-dispersed carbon nanotubes, and surfactant-assisted assemblies of graphene oxides. We found that salt and molecular crowding are both effective in condensing CNMs but the resultant structures show disparate phase behaviors. The molecular interactions driving the condensation/assembly sensitively depend on the nature of CNM complex surface chemistry and range from hydrophobic to electrostatic to entropic forces.

Host cell interactome of PA protein of H5N1 influenza A virus in chicken cells.

PubMed

Wang, Qiao; Li, Qinghe; Liu, Ranran; Zheng, Maiqing; Wen, Jie; Zhao, Guiping

2016-03-16

Influenza A virus (IAV) heavily depends on viral-host protein interactions in order to replicate and spread. Identification of host factors that interact with viral proteins plays crucial roles in understanding the mechanism of IAV infection. Here we report the interaction landscape of H5N1 IAV PA protein in chicken cells through the use of affinity purification and mass spectrometry. PA protein was expressed in chicken cells and PA interacting complexes were captured by co-immunoprecipitation and analyzed by mass spectrometry. A total of 134 proteins were identified as PA-host interacting factors. Protein complexes including the minichromosome maintenance complex (MCM), 26S proteasome and the coat protein I (COPI) complex associated with PA in chicken cells, indicating the essential roles of these functional protein complexes during the course of IAV infection. Gene Ontology and pathway enrichment analysis both showed strong enrichment of PA interacting proteins in the category of DNA replication, covering genes such as PCNA, MCM2, MCM3, MCM4, MCM5 and MCM7. This study has uncovered the comprehensive interactome of H5N1 IAV PA protein in its chicken host and helps to establish the foundation for further investigation into the newly identified viral-host interactions. Influenza A virus (IAV) is a great threat to public health and avian production. However, the manner in which avian IAV recruits the host cellular machinery for replication and how the host antagonizes the IAV infection was previously poorly understood. Here we present the viral-host interactome of the H5N1 IAV PA protein and reveal the comprehensive association of host factors with PA. Copyright © 2016 Elsevier B.V. All rights reserved.

Concerted action of Nrf2-ARE pathway, MRN complex, HMGB1 and inflammatory cytokines - Implication in modification of radiation damage

PubMed Central

Anuranjani; Bala, Madhu

2014-01-01

Whole body exposure to low linear energy transfer (LET) ionizing radiations (IRs) damages vital intracellular bio-molecules leading to multiple cellular and tissue injuries as well as pathophysiologies such as inflammation, immunosuppression etc. Nearly 70% of damage is caused indirectly by radiolysis of intracellular water leading to formation of reactive oxygen species (ROS) and free radicals and producing a state of oxidative stress. The damage is also caused by direct ionization of biomolecules. The type of radiation injuries is dependent on the absorbed radiation dose. Sub-lethal IR dose produces more of DNA base damages, whereas higher doses produce more DNA single strand break (SSBs), and double strand breaks (DSBs). The Nrf2-ARE pathway is an important oxidative stress regulating pathway. The DNA DSBs repair regulated by MRN complex, immunomodulation and inflammation regulated by HMGB1 and various types of cytokines are some of the key pathways which interact with each other in a complex manner and modify the radiation response. Because the majority of radiation damage is via oxidative stress, it is essential to gain in depth understanding of the mechanisms of Nrf2-ARE pathway and understand its interactions with MRN complex, HMGB1 and cytokines to increase our understanding on the radiation responses. Such information is of tremendous help in development of medical radiation countermeasures, radioprotective drugs and therapeutics. Till date no approved and safe countermeasure is available for human use. This study reviews the Nrf2-ARE pathway and its crosstalk with MRN-complex, HMGB1 and cytokines (TNF-a, IL-6, IFN-? etc.). An attempt is also made to review the modification of some of these pathways in presence of selected antioxidant radioprotective compounds or herbal extracts. PMID:25009785

Toward understanding of the mechanisms of Mediator function in vivo: Focus on the preinitiation complex assembly.

PubMed

Eychenne, Thomas; Werner, Michel; Soutourina, Julie

2017-01-01

Mediator is a multisubunit complex conserved in eukaryotes that plays an essential coregulator role in RNA polymerase (Pol) II transcription. Despite intensive studies of the Mediator complex, the molecular mechanisms of its function in vivo remain to be fully defined. In this review, we will discuss the different aspects of Mediator function starting with its interactions with specific transcription factors, its recruitment to chromatin and how, as a coregulator, it contributes to the assembly of transcription machinery components within the preinitiation complex (PIC) in vivo and beyond the PIC formation.

Hierarchy and Interactions in Environmental Interfaces Regarded as Biophysical Complex Systems

NASA Astrophysics Data System (ADS)

Mihailovic, Dragutin T.; Balaz, Igor

The field of environmental sciences is abundant with various interfaces and is the right place for the application of new fundamental approaches leading towards a better understanding of environmental phenomena. For example, following the definition of environmental interface by Mihailovic and Balaž [23], such interface can be placed between: human or animal bodies and surrounding air, aquatic species and water and air around them, and natural or artificially built surfaces (vegetation, ice, snow, barren soil, water, urban communities) and the atmosphere. Complex environmental interface systems are open and hierarchically organised, interactions between their constituent parts are nonlinear, and the interaction with the surrounding environment is noisy. These systems are therefore very sensitive to initial conditions, deterministic external perturbations and random fluctuations always present in nature. The study of noisy non-equilibrium processes is fundamental for modelling the dynamics of environmental interface systems and for understanding the mechanisms of spatio-temporal pattern formation in contemporary environmental sciences, particularly in environmental fluid mechanics. In modelling complex biophysical systems one of the main tasks is to successfully create an operative interface with the external environment. It should provide a robust and prompt translation of the vast diversity of external physical and/or chemical changes into a set of signals, which are "understandable" for an organism. Although the establishment of organisation in any system is of crucial importance for its functioning, it should not be forgotten that in biophysical systems we deal with real-life problems where a number of other conditions should be reached in order to put the system to work. One of them is the proper supply of the system by the energy. Therefore, we will investigate an aspect of dynamics of energy flow based on the energy balance equation. The energy as well as the exchange of biological, chemical and other physical quantities between interacting environmental interfaces can be represented by coupled maps. In this chapter we will address only two illustrative issues important for the modelling of interacting environmental interfaces regarded as complex systems. These are (i) use of algebra for modelling the autonomous establishment of local hierarchies in biophysical systems and (ii) numerical investigation of coupled maps representing exchange of energy, chemical and other relevant biophysical quantities between biophysical entities in their surrounding environment.

The role of TREX in gene expression and disease

PubMed Central

Heath, Catherine G.; Viphakone, Nicolas; Wilson, Stuart A.

2016-01-01

TRanscription and EXport (TREX) is a conserved multisubunit complex essential for embryogenesis, organogenesis and cellular differentiation throughout life. By linking transcription, mRNA processing and export together, it exerts a physiologically vital role in the gene expression pathway. In addition, this complex prevents DNA damage and regulates the cell cycle by ensuring optimal gene expression. As the extent of TREX activity in viral infections, amyotrophic lateral sclerosis and cancer emerges, the need for a greater understanding of TREX function becomes evident. A complete elucidation of the composition, function and interactions of the complex will provide the framework for understanding the molecular basis for a variety of diseases. This review details the known composition of TREX, how it is regulated and its cellular functions with an emphasis on mammalian systems. PMID:27679854

Uranium plume persistence impacted by hydrologic and geochemical heterogeneity in the groundwater and river water interaction zone of Hanford site

NASA Astrophysics Data System (ADS)

Chen, X.; Zachara, J. M.; Vermeul, V. R.; Freshley, M.; Hammond, G. E.

2015-12-01

The behavior of a persistent uranium plume in an extended groundwater- river water (GW-SW) interaction zone at the DOE Hanford site is dominantly controlled by river stage fluctuations in the adjacent Columbia River. The plume behavior is further complicated by substantial heterogeneity in physical and geochemical properties of the host aquifer sediments. Multi-scale field and laboratory experiments and reactive transport modeling were integrated to understand the complex plume behavior influenced by highly variable hydrologic and geochemical conditions in time and space. In this presentation we (1) describe multiple data sets from field-scale uranium adsorption and desorption experiments performed at our experimental well-field, (2) develop a reactive transport model that incorporates hydrologic and geochemical heterogeneities characterized from multi-scale and multi-type datasets and a surface complexation reaction network based on laboratory studies, and (3) compare the modeling and observation results to provide insights on how to refine the conceptual model and reduce prediction uncertainties. The experimental results revealed significant spatial variability in uranium adsorption/desorption behavior, while modeling demonstrated that ambient hydrologic and geochemical conditions and heterogeneities in sediment physical and chemical properties both contributed to complex plume behavior and its persistence. Our analysis provides important insights into the characterization, understanding, modeling, and remediation of groundwater contaminant plumes influenced by surface water and groundwater interactions.

Membrane interaction of antimicrobial peptides using E. coli lipid extract as model bacterial cell membranes and SFG spectroscopy.

PubMed

Soblosky, Lauren; Ramamoorthy, Ayyalusamy; Chen, Zhan

2015-04-01

Supported lipid bilayers are used as a convenient model cell membrane system to study biologically important molecule-lipid interactions in situ. However, the lipid bilayer models are often simple and the acquired results with these models may not provide all pertinent information related to a real cell membrane. In this work, we use sum frequency generation (SFG) vibrational spectroscopy to study molecular-level interactions between the antimicrobial peptides (AMPs) MSI-594, ovispirin-1 G18, magainin 2 and a simple 1,2-dipalmitoyl-d62-sn-glycero-3-phosphoglycerol (dDPPG)/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) bilayer. We compared such interactions to those between the AMPs and a more complex dDPPG/Escherichia coli (E. coli) polar lipid extract bilayer. We show that to fully understand more complex aspects of peptide-bilayer interaction, such as interaction kinetics, a heterogeneous lipid composition is required, such as the E. coli polar lipid extract. The discrepancy in peptide-bilayer interaction is likely due in part to the difference in bilayer charge between the two systems since highly negative charged lipids can promote more favorable electrostatic interactions between the peptide and lipid bilayer. Results presented in this paper indicate that more complex model bilayers are needed to accurately analyze peptide-cell membrane interactions and demonstrates the importance of using an appropriate lipid composition to study AMP interaction properties. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Identifying behaviour patterns of construction safety using system archetypes.

PubMed

Guo, Brian H W; Yiu, Tak Wing; González, Vicente A

2015-07-01

Construction safety management involves complex issues (e.g., different trades, multi-organizational project structure, constantly changing work environment, and transient workforce). Systems thinking is widely considered as an effective approach to understanding and managing the complexity. This paper aims to better understand dynamic complexity of construction safety management by exploring archetypes of construction safety. To achieve this, this paper adopted the ground theory method (GTM) and 22 interviews were conducted with participants in various positions (government safety inspector, client, health and safety manager, safety consultant, safety auditor, and safety researcher). Eight archetypes were emerged from the collected data: (1) safety regulations, (2) incentive programs, (3) procurement and safety, (4) safety management in small businesses (5) production and safety, (6) workers' conflicting goals, (7) blame on workers, and (8) reactive and proactive learning. These archetypes capture the interactions between a wide range of factors within various hierarchical levels and subsystems. As a free-standing tool, they advance the understanding of dynamic complexity of construction safety management and provide systemic insights into dealing with the complexity. They also can facilitate system dynamics modelling of construction safety process. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization of the Interaction Between Pancreatic Trypsin and an Enteric Copolymer as a Tool for Several Biotechnological Applications.

PubMed

Braia, Mauricio Javier; Loureiro, Dana Belén; Tubio, Gisela; Romanini, Diana

2015-12-01

Protein-polyelectrolyte complexes are very interesting systems since they can be applied in many long-established and emerging areas of biotechnology. From nanotechnology to industrial processing, these complexes are used for many purposes: to build multilayer particles for biosensors; to entrap and deliver proteins for pharmaceutical applications; to isolate and immobilize proteins. The enteric copolymer poly(methacrylic acid-co-methyl methacrylate) 1:2 (MMA) has been designed for drug delivery although its chemical properties allow to use it for other applications. Understanding the interaction between trypsin and this polymer is very important in order to optimize the mechanism of formation of this complex for different biotechnological applications.The formation of the trypsin-MMA complex was studied by spectroscopy and isothermal titration calorimetry. Structural analysis of trypsin was carried out by catalytic activity assays, circular dichroism and differential scanning calorimetry. Isothermal titration calorimetry experiments showed that the insoluble complex contains 12 trypsin molecules per MMA molecule at pH 5 and they interact with high affinity to form insoluble complexes. Both electrostatic and hydrophobic forces are involved in the formation of the complex. The structure of trypsin is not affected by the presence of MMA, although it interacts with some domains of trypsin affecting its thermal denaturation as seen in the differential scanning calorimetry experiments. Its catalytic activity is not altered. Dynamic light scattering demonstrated the presence of a soluble trypsin-copolymer complex at pH 5 and 8. Turbidimetric assays show that the insoluble complex can be dissolved by low ionic strength and/or pH in order to obtain free native trypsin. Copyright © 2015 Elsevier B.V. All rights reserved.

Theoretical study of X⁻ · 1 · YF (1 = triazine, X = Cl, Br and I, Y = H, Cl, Br, I, PH₂ and AsH₂): noncovalently electron-withdrawing effects on anion-arene interactions.

PubMed

Chen, Yishan; Yao, Lifeng

2014-01-01

The ternary complexes X(-) · 1 · YF (1 = triazine, X = Cl, Br and I, Y = H, Cl, Br, I, PH2 and AsH2) have been investigated by MP2 calculations to understand the noncovalently electron-withdrawing effects on anion-arene interactions. The results indicate that in binary complexes (1 · X(-)), both weak σ-type and anion-π complexes can be formed for Cl(-) and Br(-), but only anion-π complex can be formed for I(-). Moreover, the hydrogen-bonding complex is the global minimum for all three halides in binary complexes. However, in ternary complexes, anion-π complex become unstable and only σ complex can retain in many cases for Cl(-) and Br(-). Anion-π complex keeps stable only when YF = HF. In contrast with binary complexes, σ complex become the global minimum for Cl(-) and Br(-) in ternary complexes. These changes in binding mode and strength are consistent with the results of covalently electron-withdrawing effects. However, in contrast with the covalently electron-withdrawing substituents, Cl(-) and Br(-) can attack the aromatic carbon atom to form a strong σ complex when the noncovalently electron-withdrawing effect is induced by halogen bonding. The binding behavior for I(-) is different from that for Cl(-) and Br(-) in two aspects. First, the anion-π complex for I(-) can also keep stable when the noncovalent interaction is halogen bonding. Second, the anion-π complex for I(-) is the global minimum when it can retain as a stable structure.

Towards understanding the dynamic behaviour of floodplains as human-water systems

NASA Astrophysics Data System (ADS)

Di Baldassarre, G.; Kooy, M.; Kemerink, J. S.; Brandimarte, L.

2013-03-01

This paper offers a conceptual approach to explore the complex dynamics of floodplains as fully coupled human-water systems. A number of hydrologists have recently investigated the impact of human activities (such as flood control measures, land-use changes, and settlement patterns) on the frequency and severity of floods. Meanwhile, social scientists have shown how interactions between society and waters in floodplain areas, including the frequency and severity of floods, have an impact on the ways in which social relations unfold (in terms of governance processes, policies, and institutions) and societies are organised (spatially, politically, and socially). However, we argue that the interactions and associated feedback mechanisms between hydrological and social processes remain largely unexplored and poorly understood. Thus, there is a need to better understand how the institutions and governance processes interact with hydrological processes in floodplains to influence the frequency and severity of floods, while (in turn) hydrological processes co-constitute the social realm and make a difference for how social relations unfold to shape governance processes and institutions. Our research goal, therefore, is not in identifying one or the other side of the cycle (hydrological or social), but in explaining the relationship between them: how, when, where, and why they interact, and to what result for both social relations and hydrological processes? We argue that long time series of hydrological and social data, along with remote sensing data, can be used to observe floodplain dynamics from unconventional approaches, and understand the complex interactions between water and human systems taking place in floodplain areas, across scales and levels of human impacts, and within different hydro-climatic conditions, socio-cultural settings, and modes of governance.

Towards understanding the dynamic behaviour of floodplains as human-water systems

NASA Astrophysics Data System (ADS)

Di Baldassarre, G.; Kooy, M.; Kemerink, J. S.; Brandimarte, L.

2013-08-01

This paper offers a conceptual approach to explore the complex dynamics of floodplains as fully coupled human-water systems. A number of hydrologists have recently investigated the impact of human activities (such as flood control measures, land-use changes, and settlement patterns) on the frequency and severity of floods. Meanwhile, social scientists have shown how interactions between society and waters in deltas and floodplain areas, including the frequency and severity of floods, have an impact on the ways in which social relations unfold (in terms of governance processes, policies, and institutions) and societies are organised (spatially, politically, and socially). However, we argue that the interactions and associated feedback mechanisms between hydrological and social processes remain largely unexplored and poorly understood. Thus, there is a need to better understand how the institutions and governance processes interact with hydrological processes in deltas and floodplains to influence the frequency and severity of floods, while (in turn) hydrological processes co-constitute the social realm and make a difference for how social relations unfold to shape governance processes and institutions. Our research goal, therefore, is not in identifying one or the other side of the cycle (hydrological or social), but in explaining the relationship between them: how, when, where, and why they interact, and to what result for both social relations and hydrological processes? We argue that long time series of hydrological and social data, along with remote sensing data, can be used to observe floodplain dynamics from unconventional approaches, and understand the complex interactions between water and human systems taking place in floodplain areas, across scales and levels of human impacts, and within different hydro-climatic conditions, socio-cultural settings, and modes of governance.

A computational interactome for prioritizing genes associated with complex agronomic traits in rice (Oryza sativa).

PubMed

Liu, Shiwei; Liu, Yihui; Zhao, Jiawei; Cai, Shitao; Qian, Hongmei; Zuo, Kaijing; Zhao, Lingxia; Zhang, Lida

2017-04-01

Rice (Oryza sativa) is one of the most important staple foods for more than half of the global population. Many rice traits are quantitative, complex and controlled by multiple interacting genes. Thus, a full understanding of genetic relationships will be critical to systematically identify genes controlling agronomic traits. We developed a genome-wide rice protein-protein interaction network (RicePPINet, http://netbio.sjtu.edu.cn/riceppinet) using machine learning with structural relationship and functional information. RicePPINet contained 708 819 predicted interactions for 16 895 non-transposable element related proteins. The power of the network for discovering novel protein interactions was demonstrated through comparison with other publicly available protein-protein interaction (PPI) prediction methods, and by experimentally determined PPI data sets. Furthermore, global analysis of domain-mediated interactions revealed RicePPINet accurately reflects PPIs at the domain level. Our studies showed the efficiency of the RicePPINet-based method in prioritizing candidate genes involved in complex agronomic traits, such as disease resistance and drought tolerance, was approximately 2-11 times better than random prediction. RicePPINet provides an expanded landscape of computational interactome for the genetic dissection of agronomically important traits in rice. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Recovery of an HMWP/hmwBP (pUL48/pUL47) complex from virions of human cytomegalovirus: subunit interactions, oligomer composition, and deubiquitylase activity.

PubMed

Tullman, Jennifer A; Harmon, Mary-Elizabeth; Delannoy, Michael; Gibson, Wade

2014-08-01

We report that the human cytomegalovirus (HCMV) high-molecular-weight tegument protein (HMWP, pUL48; 253 kDa) and the HMWP-binding protein (hmwBP, pUL47; 110 kDa) can be recovered as a complex from virions disrupted by treatment with 50 mM Tris (pH 7.5), 0.5 M NaCl, 0.5% NP-40, and 10 mM dithiothreitol [DTT]. The subunit ratio of the complex approximates 1:1, with a shape and structure consistent with an elongated heterodimer. The HMWP/hmwBP complex was corroborated by reciprocal coimmunoprecipitation experiments using antipeptide antibodies and lysates from both infected cells and disrupted virus particles. An interaction of the amino end of pUL48 (amino acids [aa] 322 to 754) with the carboxyl end of pUL47 (aa 693 to 982) was identified by fragment coimmunoprecipitation experiments, and a head-to-tail self-interaction of hmwBP was also observed. The deubiquitylating activity of pUL48 is retained in the isolated complex, which cleaves K11, K48, and K63 ubiquitin isopeptide linkages. Human cytomegalovirus (HCMV, or human herpesvirus 5 [HHV-5]) is a large DNA-containing virus that belongs to the betaherpesvirus subfamily and is a clinically important pathogen. Defining the constituent elements of its mature form, their organization within the particle, and the assembly process by which it is produced are fundamental to understanding the mechanisms of herpesvirus infection and developing drugs and vaccines against them. In this study, we report isolating a complex of two large proteins encoded by HCMV open reading frames (ORFs) UL47 and UL48 and identifying the binding domains responsible for their interaction with each other and of pUL47 with itself. Our calculations indicate that the complex is a rod-shaped heterodimer. Additionally, we determined that the ubiquitin-specific protease activity of the ORF UL48 protein was functional in the complex, cleaving K11-, K48-, and K63-linked ubiquitin dimers. This information builds on and extends our understanding of the HCMV tegument protein network that is required to interface the HCMV envelope and capsid. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Polycomb purification by in vivo biotinylation tagging reveals cohesin and Trithorax group proteins as interaction partners

PubMed Central

Strübbe, Gero; Popp, Christian; Schmidt, Alexander; Pauli, Andrea; Ringrose, Leonie; Beisel, Christian; Paro, Renato

2011-01-01

The maintenance of specific gene expression patterns during cellular proliferation is crucial for the identity of every cell type and the development of tissues in multicellular organisms. Such a cellular memory function is conveyed by the complex interplay of the Polycomb and Trithorax groups of proteins (PcG/TrxG). These proteins exert their function at the level of chromatin by establishing and maintaining repressed (PcG) and active (TrxG) chromatin domains. Past studies indicated that a core PcG protein complex is potentially associated with cell type or even cell stage-specific sets of accessory proteins. In order to better understand the dynamic aspects underlying PcG composition and function we have established an inducible version of the biotinylation tagging approach to purify Polycomb and associated factors from Drosophila embryos. This system enabled fast and efficient isolation of Polycomb containing complexes under near physiological conditions, thereby preserving substoichiometric interactions. Novel interacting proteins were identified by highly sensitive mass spectrometric analysis. We found many TrxG related proteins, suggesting a previously unrecognized extent of molecular interaction of the two counteracting chromatin regulatory protein groups. Furthermore, our analysis revealed an association of PcG protein complexes with the cohesin complex and showed that Polycomb-dependent silencing of a transgenic reporter depends on cohesin function. PMID:21415365

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

Scott, F.; Stec, B; Pop, C

The death inducing signalling complex (DISC) formed by Fas receptor, FADD (Fas-associated death domain protein) and caspase 8 is a pivotal trigger of apoptosis1, 2, 3. The Fas-FADD DISC represents a receptor platform, which once assembled initiates the induction of programmed cell death. A highly oligomeric network of homotypic protein interactions comprised of the death domains of Fas and FADD is at the centre of DISC formation4, 5. Thus, characterizing the mechanistic basis for the Fas-FADD interaction is crucial for understanding DISC signalling but has remained unclear largely because of a lack of structural data. We have successfully formed andmore » isolated the human Fas-FADD death domain complex and report the 2.7 A crystal structure. The complex shows a tetrameric arrangement of four FADD death domains bound to four Fas death domains. We show that an opening of the Fas death domain exposes the FADD binding site and simultaneously generates a Fas-Fas bridge. The result is a regulatory Fas-FADD complex bridge governed by weak protein-protein interactions revealing a model where the complex itself functions as a mechanistic switch. This switch prevents accidental DISC assembly, yet allows for highly processive DISC formation and clustering upon a sufficient stimulus. In addition to depicting a previously unknown mode of death domain interactions, these results further uncover a mechanism for receptor signalling solely by oligomerization and clustering events.« less

[Molecular dynamics of immune complex of photoadduct-containing DNA with Fab-Anti-DNA antibody fragment].

PubMed

Akberova, N I; Zhmurov, A A; Nevzorova, T A; Litvinov, R I

2016-01-01

Antibodies to DNA play an important role in the pathogenesis of autoimmune diseases. The elucidation of structural mechanisms of both the antigen recognition and the interaction of anti-DNA antibodies with DNA will help to understand the role of DNA-containing immune complexes in various pathologies and can provide a basis for new treatment modalities. Moreover, the DNA-antibody complex is an analog of specific intracellular DNA-protein interactions. In this work, we used in silico molecular dynamic simulations of bimolecular complexes of the dsDNA segment containing the Fab fragment of an anti-DNA antibody to obtain the detailed thermodynamic and structural characteristics of dynamic intermolecular interactions. Using computationally modified crystal structure of the Fab-DNA complex (PDB ID: 3VW3), we studied the equilibrium molecular dynamics of the 64M-5 antibody Fab fragment associated with the dsDNA fragment containing the thymine dimer, the product of DNA photodamage. Amino acid residues that constitute paratopes and the complementary nucleotide epitopes for the Fab-DNA construct were identified. Stacking and electrostatic interactions were found to play the main role in mediating the most specific antibody-dsDNA contacts, while hydrogen bonds were less significant. These findings may shed light on the formation and properties of pathogenic anti-DNA antibodies in autoimmune diseases, such as systemic lupus erythematosus associated with skin photosensitivity and DNA photodamage.

The role of future scenarios to understand deep uncertainty

EPA Science Inventory

The environment and its interaction with human systems(economic, social and political) is complex and dynamic. Key drivers may disrupt system dynamics in unforeseen ways, making it difficult to predict future conditions precisely. This kind of deep uncertainty presents a challe...

Climate metrics and aviation : analysis of current understanding and uncertainties

DOT National Transportation Integrated Search

2008-01-22

The impact of climate-altering agents on the atmospheric system is a result of a complex system : of interactions and feedbacks within the atmosphere, and with the oceans, the land surface, the : biosphere and the cryosphere. Climate metrics are used...

Games and Simulation.

ERIC Educational Resources Information Center

Abt, Clark C.

Educational games present the complex realities of simultaneous interactive processes more accurately and effectively than serial processes such as lecturing and reading. Objectives of educational gaming are to motivate students by presenting relevant and realistic problems and to induce more efficient and active understanding of information.…

Statistical Accounting for Uncertainty in Modeling Transport in Environmental Systems

EPA Science Inventory

Models frequently are used to predict the future extent of ground-water contamination, given estimates of their input parameters and forcing functions. Although models have a well established scientific basis for understanding the interactions between complex phenomena and for g...

Microbial Adhesion and Biofilm Formation on Microfiltration Membranes: A Detailed Characterization Using Model Organisms with Increasing Complexity

PubMed Central

Vanysacker, L.; Denis, C.; Declerck, P.; Piasecka, A.; Vankelecom, I. F. J.

2013-01-01

Since many years, membrane biofouling has been described as the Achilles heel of membrane fouling. In the present study, an ecological assay was performed using model systems with increasing complexity: a monospecies assay using Pseudomonas aeruginosa or Escherichia coli separately, a duospecies assay using both microorganisms, and a multispecies assay using activated sludge with or without spiked P. aeruginosa. The microbial adhesion and biofilm formation were evaluated in terms of bacterial cell densities, species richness, and bacterial community composition on polyvinyldifluoride, polyethylene, and polysulfone membranes. The data show that biofouling formation was strongly influenced by the kind of microorganism, the interactions between the organisms, and the changes in environmental conditions whereas the membrane effect was less important. The findings obtained in this study suggest that more knowledge in species composition and microbial interactions is needed in order to understand the complex biofouling process. This is the first report describing the microbial interactions with a membrane during the biofouling development. PMID:23986906

Label-Free Discovery Array Platform for the Characterization of Glycan Binding Proteins and Glycoproteins.

PubMed

Gray, Christopher J; Sánchez-Ruíz, Antonio; Šardzíková, Ivana; Ahmed, Yassir A; Miller, Rebecca L; Reyes Martinez, Juana E; Pallister, Edward; Huang, Kun; Both, Peter; Hartmann, Mirja; Roberts, Hannah N; Šardzík, Robert; Mandal, Santanu; Turnbull, Jerry E; Eyers, Claire E; Flitsch, Sabine L

2017-04-18

The identification of carbohydrate-protein interactions is central to our understanding of the roles of cell-surface carbohydrates (the glycocalyx), fundamental for cell-recognition events. Therefore, there is a need for fast high-throughput biochemical tools to capture the complexity of these biological interactions. Here, we describe a rapid method for qualitative label-free detection of carbohydrate-protein interactions on arrays of simple synthetic glycans, more complex natural glycosaminoglycans (GAG), and lectins/carbohydrate binding proteins using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The platform can unequivocally identify proteins that are captured from either purified or complex sample mixtures, including biofluids. Identification of proteins bound to the functionalized array is achieved by analyzing either the intact protein mass or, after on-chip proteolytic digestion, the peptide mass fingerprint and/or tandem mass spectrometry of selected peptides, which can yield highly diagnostic sequence information. The platform described here should be a valuable addition to the limited analytical toolbox that is currently available for glycomics.

Interaction of gold nanoparticles with free radicals and their role in enhancing the scavenging activity of ascorbic acid.

PubMed

Razzaq, Humaira; Saira, Farhat; Yaqub, Azra; Qureshi, Rumana; Mumtaz, Misbah; Saleemi, Samia

2016-08-01

The present study investigates the interaction of citrate stabilized gold nanoparticles (12±1.5nm) (GNPs) with free radicals; 1,1-diphenyl-2-picrylhydrazyl (DPPH) stable and electrochemically generated superoxide, O2(-). Different experiments were designed to understand the interaction between GNPs and DPPH by employing cyclic voltammetry, UV-vis spectroscopy and computational chemistry using 6-311G basis set. The increase in heterogeneous rate constant, ksh, of DPPH upon addition of GNPs pointed towards possible complex formation, DPPH-GNPs which were further explained by a model assuming surface adsorption of DPPH on GNPs. Further, the model was validated by studying interaction of GNPs with a biologically important free radical, O2(-). Exciting result in terms of disappearance of anodic peak after GNPs addition confirmed that gold nanoparticles interacted with stable as well as unstable free radicals. Also, the stoichiometry of the most stable complex GNP-DPPH was determined from UV-vis spectroscopy by applying Job's method. The GNP-DPPH complex was found to be active with 46.0% reduction of the IC50 value of standard antioxidant, ascorbic acid (AA), indicating its role in enhancing antioxidant activity. Hence, this study presents a simple and potential approach to enhance the efficiency of natural antioxidants without modifying their structure, or involving the complex functionalization of GNPs with antioxidants. Copyright © 2016. Published by Elsevier B.V.

Saponin Interactions with Model Membrane Systems - Langmuir Monolayer Studies, Hemolysis and Formation of ISCOMs.

PubMed

de Groot, Carolin; Müller-Goymann, Christel C

2016-12-01

Saponins are used in medicine due to their pharmacological and immunological effects. To better understand interactions of saponins with model membranes and natural membranes of, for example, erythrocytes, Langmuir film balance experiments are well established. For most saponins, a strong interaction with cholesterol was demonstrated in dependence of both the aglycone part and the sugar moieties and is suggested to be correlated with a strong hemolytic activity, high toxicity, and high surface activity, as was demonstrated for the steroid saponin digitonin. In general, changes in the sugar chain or in substituents of the aglycone result in a modification of the saponin properties. A promising saponin with regard to fairly low hemolytic activity and high adjuvant effect is α -tomatine, which still shows a high affinity for cholesterol. An interaction with cholesterol and lipids has also been proven for the Quillaja saponin from the bark of Quillaja saponaria Molina. This triterpene saponin was approved in marketed vaccines as an adjuvant due to the formation of immunostimulating complexes. Immunostimulating complexes consist of a Quillaja saponin, cholesterol, phospholipids, and a corresponding antigen. Recently, another saponin from Quillaja brasiliensis was successfully tested in immunostimulating complexes, too. Based on the results of interaction studies, the formation of drug delivery systems such as immunostimulating complexes or similar self-assembled colloids is postulated for a variety of saponins. Georg Thieme Verlag KG Stuttgart · New York.

Effect of PDGF-B aptamer on PDGFRβ/PDGF-B interaction: Molecular dynamics study.

PubMed

Vu, Cong Quang; Rotkrua, Pichayanoot; Soontornworajit, Boonchoy; Tantirungrotechai, Yuthana

2018-06-01

PDGFRβ/PDGF-B interaction plays a role in angiogenesis, and is mandatory in wound healing and cancer treatment. It has been reported that the PDGF-B aptamer was able to bind to PDGF-B, thus regulating the angiogenesis. However, the binding interaction between the aptamer and the growth factor, including the binding sites, has not been well investigated. This study applied a molecular dynamics (MD) simulation to investigate the aptamer-growth factor interaction in the presence or absence of a receptor (PDGFRβ). Characterization of the structure of an aptamer-growth factor complex revealed binding sites from each section in the complex. Upon the complex formation, PDGF-B and its aptamer exhibited less flexibility in their molecular movement, as indicated by the minimum values of RMSD, RMSF, loop-to-loop distance, and the summation of PCA eigenvalues. Our study of residue pairwise interaction demonstrated that the binding interaction was mainly contributed by electrostatic interaction between the positively-charged amino acid and the negatively-charged phosphate backbone. The role of the PDGF-B aptamer in PDGFRβ/PDGF-B interaction was also investigated. We demonstrated that the stability of the Apt-PDGF-B complex could prevent the presence of a competitor, of PDGFRβ, interrupting the binding process. Because the aptamer was capable of binding with PDGF-B, and blocking the growth factor from the PDGFRβ, it could down regulate the consequent signaling pathway. We provide evidence that the PDGF-BB aptamer is a promising molecule for regulation of angiogenesis. The MD study provides a molecular understanding to modification of the aptamer binding interaction, which could be used in a number of medical applications. Copyright © 2018 Elsevier Inc. All rights reserved.

Crystallographic study of FABP5 as an intracellular endocannabinoid transporter

PubMed Central

Sanson, Benoît; Wang, Tao; Sun, Jing; Wang, Liqun; Kaczocha, Martin; Ojima, Iwao; Deutsch, Dale; Li, Huilin

2014-01-01

In addition to binding intracellular fatty acids, fatty-acid-binding proteins (FABPs) have recently been reported to also transport the endocannabinoids anandamide (AEA) and 2-­arachidonoylglycerol (2-AG), arachidonic acid derivatives that function as neurotransmitters and mediate a diverse set of physiological and psychological processes. To understand how the endocannabinoids bind to FABPs, the crystal structures of FABP5 in complex with AEA, 2-AG and the inhibitor BMS-309403 were determined. These ligands are shown to interact primarily with the substrate-binding pocket via hydrophobic interactions as well as a common hydrogen bond to the Tyr131 residue. This work advances our understanding of FABP5–endocannabinoid interactions and may be useful for future efforts in the development of small-molecule inhibitors to raise endocannabinoid levels. PMID:24531463

Aspergillus fumigatus morphology and dynamic host interactions.

PubMed

van de Veerdonk, Frank L; Gresnigt, Mark S; Romani, Luigina; Netea, Mihai G; Latgé, Jean-Paul

2017-11-01

Aspergillus fumigatus is an environmental filamentous fungus that can cause life-threatening disease in immunocompromised individuals. The interactions between A. fumigatus and the host environment are dynamic and complex. The host immune system needs to recognize the distinct morphological forms of A. fumigatus to control fungal growth and prevent tissue invasion, whereas the fungus requires nutrients and needs to adapt to the hostile environment by escaping immune recognition and counteracting host responses. Understanding these highly dynamic interactions is necessary to fully understand the pathogenesis of aspergillosis and to facilitate the design of new therapeutics to overcome the morbidity and mortality caused by A. fumigatus. In this Review, we describe how A. fumigatus adapts to environmental change, the mechanisms of host defence, and our current knowledge of the interplay between the host immune response and the fungus.

3D microvascular model recapitulates the diffuse large B-cell lymphoma tumor microenvironment in vitro.

PubMed

Mannino, Robert G; Santiago-Miranda, Adriana N; Pradhan, Pallab; Qiu, Yongzhi; Mejias, Joscelyn C; Neelapu, Sattva S; Roy, Krishnendu; Lam, Wilbur A

2017-01-31

Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer that affects ∼22 000 people in the United States yearly. Understanding the complex cellular interactions of the tumor microenvironment is critical to the success and development of DLBCL treatment strategies. In vitro platforms that successfully model the complex tumor microenvironment without introducing the variability of in vivo systems are vital for understanding these interactions. To date, no such in vitro model exists that can accurately recapitulate the interactions that occur between immune cells, cancer cells, and endothelial cells in the tumor microenvironment of DLBCL. To that end, we developed a lymphoma-on-chip model consisting of a hydrogel based tumor model traversed by a vascularized, perfusable, round microchannel that successfully recapitulates key complexities and interactions of the in vivo tumor microenvironment in vitro. We have shown that the perfusion capabilities of this technique allow us to study targeted treatment strategies, as well as to model the diffusion of infused reagents spatiotemporally. Furthermore, this model employs a novel fabrication technique that utilizes common laboratory materials, and allows for the microfabrication of multiplex microvascular environments without the need for advanced microfabrication facilities. Through our facile microfabrication process, we are able to achieve micro vessels within a tumor model that are highly reliable and precise over the length of the vessel. Overall, we have developed a tool that enables researchers from many diverse disciplines to study previously inaccessible aspects of the DLBCL tumor microenvironment, with profound implications for drug delivery and design.

3D microvascular model recapitulates the diffuse large B-cell lymphoma tumor microenvironment in vitro

PubMed Central

Mannino, Robert G.; Santiago-Miranda, Adriana N.; Pradhan, Pallab; Qiu, Yongzhi; Mejias, Joscelyn C.; Neelapu, Sattva S.; Roy, Krishnendu; Lam, Wilbur A.

2017-01-01

Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer that affects ~22,000 people in the United States yearly. Understanding the complex cellular interactions of the tumor microenvironment is critical to the success and development of DLBCL treatment strategies. In vitro platforms that successfully model the complex tumor microenvironment without introducing the variability of in vivo systems are vital for understanding these interactions. To date, no such in vitro model exists that can accurately recapitulate the interactions that occur between immune cells, cancer cells, and endothelial cells in the tumor microenvironment of DLBCL. To that end, we developed a lymphoma-on-chip model consisting of a hydrogel based tumor model traversed by a vascularized, perfusable, round microchannel that successfully recapitulates key complexities and interactions of the in vivo tumor microenvironment in vitro. We have shown that the perfusion capabilities of this technique allow us to study targeted treatment strategies, as well as to model the diffusion of infused reagents spatiotemporally. Furthermore, this model employs a novel fabrication technique that utilizes common laboratory materials, and allows for the microfabrication of multiplex microvascular environments without the need for advanced microfabrication facilities. Through our facile microfabrication process, we are able to achieve micro vessels within a tumor model that are highly reliable and precise over the length of the vessel. Overall, we have developed a tool that enables researchers from many diverse disciplines to study previously inaccessible aspects of the DLBCL tumor microenvironment, with profound implications for drug delivery and design. PMID:28054086

A Nonlinear Model for Gene-Based Gene-Environment Interaction.

PubMed

Sa, Jian; Liu, Xu; He, Tao; Liu, Guifen; Cui, Yuehua

2016-06-04

A vast amount of literature has confirmed the role of gene-environment (G×E) interaction in the etiology of complex human diseases. Traditional methods are predominantly focused on the analysis of interaction between a single nucleotide polymorphism (SNP) and an environmental variable. Given that genes are the functional units, it is crucial to understand how gene effects (rather than single SNP effects) are influenced by an environmental variable to affect disease risk. Motivated by the increasing awareness of the power of gene-based association analysis over single variant based approach, in this work, we proposed a sparse principle component regression (sPCR) model to understand the gene-based G×E interaction effect on complex disease. We first extracted the sparse principal components for SNPs in a gene, then the effect of each principal component was modeled by a varying-coefficient (VC) model. The model can jointly model variants in a gene in which their effects are nonlinearly influenced by an environmental variable. In addition, the varying-coefficient sPCR (VC-sPCR) model has nice interpretation property since the sparsity on the principal component loadings can tell the relative importance of the corresponding SNPs in each component. We applied our method to a human birth weight dataset in Thai population. We analyzed 12,005 genes across 22 chromosomes and found one significant interaction effect using the Bonferroni correction method and one suggestive interaction. The model performance was further evaluated through simulation studies. Our model provides a system approach to evaluate gene-based G×E interaction.

Exploring Market State and Stock Interactions on the Minute Timescale

PubMed Central

Tan, Lei; Chen, Jun-Jie; Zheng, Bo; Ouyang, Fang-Yan

2016-01-01

A stock market is a non-stationary complex system. The stock interactions are important for understanding the state of the market. However, our knowledge on the stock interactions on the minute timescale is limited. Here we apply the random matrix theory and methods in complex networks to study the stock interactions and sector interactions. Further, we construct a new kind of cross-correlation matrix to investigate the correlation between the stock interactions at different minutes within one trading day. Based on 50 million minute-to-minute price data in the Shanghai stock market, we discover that the market states in the morning and afternoon are significantly different. The differences mainly exist in three aspects, i.e. the co-movement of stock prices, interactions of sectors and correlation between the stock interactions at different minutes. In the afternoon, the component stocks of sectors are more robust and the structure of sectors is firmer. Therefore, the market state in the afternoon is more stable. Furthermore, we reveal that the information of the sector interactions can indicate the financial crisis in the market, and the indicator based on the empirical data in the afternoon is more effective. PMID:26900948

Exploring Market State and Stock Interactions on the Minute Timescale.

PubMed

Tan, Lei; Chen, Jun-Jie; Zheng, Bo; Ouyang, Fang-Yan

2016-01-01

A stock market is a non-stationary complex system. The stock interactions are important for understanding the state of the market. However, our knowledge on the stock interactions on the minute timescale is limited. Here we apply the random matrix theory and methods in complex networks to study the stock interactions and sector interactions. Further, we construct a new kind of cross-correlation matrix to investigate the correlation between the stock interactions at different minutes within one trading day. Based on 50 million minute-to-minute price data in the Shanghai stock market, we discover that the market states in the morning and afternoon are significantly different. The differences mainly exist in three aspects, i.e. the co-movement of stock prices, interactions of sectors and correlation between the stock interactions at different minutes. In the afternoon, the component stocks of sectors are more robust and the structure of sectors is firmer. Therefore, the market state in the afternoon is more stable. Furthermore, we reveal that the information of the sector interactions can indicate the financial crisis in the market, and the indicator based on the empirical data in the afternoon is more effective.

Peripheral stator of the yeast V-ATPase: stoichiometry and specificity of interaction between the EG complex and subunits C and H.

PubMed

Féthière, James; Venzke, David; Madden, Dean R; Böttcher, Bettina

2005-12-06

V-ATPases are multisubunit membrane protein complexes that use the energy provided by ATP hydrolysis to generate a proton gradient across various intracellular and plasma membranes. In doing so, they maintain an acidic pH in the lumen of intracellular organelles and acidify extracellular milieu to support specific cellular functions. V-ATPases are structurally similar to the F1F0-ATP synthase, with an intrinsic membrane domain (V0) and an extrinsic peripheral domain (V1) joined by several connecting elements. To gain a clear functional understanding of the catalytic mechanism, and of the stability requirements for regulatory processes in the enzyme, a clear topology of the enzyme has to be established. In particular, the composition and arrangement of the peripheral stator subunits must be firmly settled, as these play specific roles in catalysis and regulation. We have designed a strategy allowing us to coexpress different combinations of these subunits to delineate specific interactions. In this study, we report the interaction between the peripheral stator EG complex and subunits C and H of the V-ATPase from the yeast Saccharomyces cerevisae. A combination of analytical gel filtration, native gel electrophoresis, and ultracentrifugation analysis allowed us to ascertain the homogeneity and molar mass of the purified EGC complex as well as of the EG complex, supporting the formation of 1:1(:1) stoichiometric complexes. The EGC complex can be formed in vitro by combining equimolar amounts of subunit C and the EG subcomplex and results most likely from the initial interaction between subunits E and C.

Biotic interactions as drivers of algal origin and evolution.

PubMed

Brodie, Juliet; Ball, Steven G; Bouget, François-Yves; Chan, Cheong Xin; De Clerck, Olivier; Cock, J Mark; Gachon, Claire; Grossman, Arthur R; Mock, Thomas; Raven, John A; Saha, Mahasweta; Smith, Alison G; Vardi, Assaf; Yoon, Hwan Su; Bhattacharya, Debashish

2017-11-01

Contents 670 I. 671 II. 671 III. 676 IV. 678 678 References 678 SUMMARY: Biotic interactions underlie life's diversity and are the lynchpin to understanding its complexity and resilience within an ecological niche. Algal biologists have embraced this paradigm, and studies building on the explosive growth in omics and cell biology methods have facilitated the in-depth analysis of nonmodel organisms and communities from a variety of ecosystems. In turn, these advances have enabled a major revision of our understanding of the origin and evolution of photosynthesis in eukaryotes, bacterial-algal interactions, control of massive algal blooms in the ocean, and the maintenance and degradation of coral reefs. Here, we review some of the most exciting developments in the field of algal biotic interactions and identify challenges for scientists in the coming years. We foresee the development of an algal knowledgebase that integrates ecosystem-wide omics data and the development of molecular tools/resources to perform functional analyses of individuals in isolation and in populations. These assets will allow us to move beyond mechanistic studies of a single species towards understanding the interactions amongst algae and other organisms in both the laboratory and the field. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Plant Phenotyping through the Eyes of Complex Systems: Theoretical Considerations

NASA Astrophysics Data System (ADS)

Kim, J.

2017-12-01

Plant phenotyping is an emerging transdisciplinary research which necessitates not only the communication and collaboration of scientists from different disciplines but also the paradigm shift to a holistic approach. Complex system is defined as a system having a large number of interacting parts (or particles, agents), whose interactions give rise to non-trivial properties like self-organization and emergence. Plant ecosystems are complex systems which are continually morphing dynamical systems, i.e. self-organizing hierarchical open systems. Such systems are composed of many subunits/subsystems with nonlinear interactions and feedback. The throughput such as the flow of energy, matter and information is the key control parameter in complex systems. Information theoretic approaches can be used to understand and identify such interactions, structures and dynamics through reductions in uncertainty (i.e. entropy). The theoretical considerations based on network and thermodynamic thinking and exemplary analyses (e.g. dynamic process network, spectral entropy) of the throughput time series will be presented. These can be used as a framework to develop more discipline-specific fundamental approaches to provide tools for the transferability of traits between measurement scales in plant phenotyping. Acknowledgment: This work was funded by the Weather Information Service Engine Program of the Korea Meteorological Administration under Grant KMIPA-2012-0001.

Emotional valence and context of social influences on drug abuse-related behavior in animal models of social stress and prosocial interaction.

PubMed

Neisewander, J L; Peartree, N A; Pentkowski, N S

2012-11-01

Social factors are important determinants of drug dependence and relapse. We reviewed pre-clinical literature examining the role of social experiences from early life through the development of drug dependence and relapse, emphasizing two aspects of these experiences: (1) whether the social interaction is appetitive or aversive and (2) whether the social interaction occurs within or outside of the drug-taking context. The models reviewed include neonatal care, isolation, social defeat, chronic subordination, and prosocial interactions. We review results from these models in regard to effects on self-administration and conditioned place preference established with alcohol, psychostimulants, and opiates. We suggest that in general, when the interactions occur outside of the drug-taking context, prosocial interactions are protective against drug abuse-related behaviors, whereas social stressors facilitate these behaviors. By contrast, positive or negative social interactions occurring within the drug-taking context may interact with other risk factors to enhance or inhibit these behaviors. Despite differences in the nature and complexity of human social behavior compared to other species, the evolving animal literature provides useful models for understanding social influences on drug abuse-related behavior that will allow for research on the behavioral and biological mechanisms involved. The models have contributed to understanding social influences on initiation and maintenance of drug use, but more research is needed to understand social influences on drug relapse.

Combustion and Magnetohydrodynamic Processes in Advanced Pulse Detonation Rocket Engines

DTIC Science & Technology

2012-10-01

use of high-order numerical methods can also be a powerful tool in the analysis of such complex flows, but we need to understand the interaction of...computational physics, 43(2):357372, 1981. [47] B. Einfeldt. On godunov-type methods for gas dynamics . SIAM Journal on Numerical Analysis , pages 294...dimensional effects with complex reaction kinetics, the simple one-dimensional detonation structure provides a rich spectrum of dynamical features which are

Data Science in the Research Domain Criteria Era: Relevance of Machine Learning to the Study of Stress Pathology, Recovery, and Resilience

PubMed Central

Galatzer-Levy, Isaac R.; Ruggles, Kelly; Chen, Zhe

2017-01-01

Diverse environmental and biological systems interact to influence individual differences in response to environmental stress. Understanding the nature of these complex relationships can enhance the development of methods to: (1) identify risk, (2) classify individuals as healthy or ill, (3) understand mechanisms of change, and (4) develop effective treatments. The Research Domain Criteria (RDoC) initiative provides a theoretical framework to understand health and illness as the product of multiple inter-related systems but does not provide a framework to characterize or statistically evaluate such complex relationships. Characterizing and statistically evaluating models that integrate multiple levels (e.g. synapses, genes, environmental factors) as they relate to outcomes that a free from prior diagnostic benchmarks represents a challenge requiring new computational tools that are capable to capture complex relationships and identify clinically relevant populations. In the current review, we will summarize machine learning methods that can achieve these goals. PMID:29527592

Investigation of Stimulation-Response Relationships for Complex Fracture Systems in Enhanced Geothermal Reservoirs

DOE Data Explorer

Fu, Pengcheng; Johnson, Scott M.; Carrigan, Charles R.

2011-01-01

Hydraulic fracturing is currently the primary method for stimulating low-permeability geothermal reservoirs and creating Enhanced (or Engineered) Geothermal Systems (EGS) with improved permeability and heat production efficiency. Complex natural fracture systems usually exist in the formations to be stimulated and it is therefore critical to understand the interactions between existing fractures and newly created fractures before optimal stimulation strategies can be developed. Our study aims to improve the understanding of EGS stimulation-response relationships by developing and applying computer-based models that can effectively reflect the key mechanisms governing interactions between complex existing fracture networks and newly created hydraulic fractures. In this paper, we first briefly describe the key modules of our methodology, namely a geomechanics solver, a discrete fracture flow solver, a rock joint response model, an adaptive remeshing module, and most importantly their effective coupling. After verifying the numerical model against classical closed-form solutions, we investigate responses of reservoirs with different preexisting natural fractures to a variety of stimulation strategies. The factors investigated include: the in situ stress states (orientation of the principal stresses and the degree of stress anisotropy), pumping pressure, and stimulation sequences of multiple wells.

A complex adaptive systems perspective of health information technology implementation.

PubMed

Keshavjee, Karim; Kuziemsky, Craig; Vassanji, Karim; Ghany, Ahmad

2013-01-01

Implementing health information technology (HIT) is a challenge because of the complexity and multiple interactions that define HIT implementation. Much of the research on HIT implementation is descriptive in nature and has focused on distinct processes such as order entry or decision support. These studies fail to take into account the underlying complexity of the processes, people and settings that are typical of HIT implementations. Complex adaptive systems (CAS) is a promising field that could elucidate the complexity and non-linear interacting issues that are typical in HIT implementation. Initially we sought new models that would enable us to better understand the complex nature of HIT implementation, to proactively identify problem issues that could be a precursor to unintended consequences and to develop new models and new approaches to successful HIT implementations. Our investigation demonstrates that CAS does not provide prediction, but forces us to rethink our HIT implementation paradigms and question what we think we know. CAS provides new ways to conceptualize HIT implementation and suggests new approaches to increasing HIT implementation successes.

Proteomic analysis of a model fish species exposed to individual pesticides and a binary mixture

EPA Science Inventory

Aquatic organisms are often exposed to multiple pesticides simultaneously. Due to the relatively poor characterization of mixture constituent interactions and the potential for highly complex exposure scenarios, there is considerable uncertainty in understanding the toxicity of m...

The role of future scenarios to understand deep uncertainty in air quality management

EPA Science Inventory

The environment and it’s interaction with human systems (economic, social and political) is complex and dynamic. Key drivers may disrupt system dynamics in unforeseen ways, making it difficult to predict future conditions precisely. This kind of deep uncertainty presents ...

The role of future scenarios to understand deep uncertainty for air quality management.

EPA Science Inventory

The environment and its interaction with human systems (economic, social and political) is complex and dynamic. Key drivers may disrupt systemdynamics in unforeseen ways, making it difficult to predict future conditions precisely. This kind of deep uncertainty presents a challeng...

Hydrological modeling in forested systems

Treesearch

H.E. Golden; G.R. Evenson; S. Tian; Devendra Amatya; Ge Sun

2015-01-01

Characterizing and quantifying interactions among components of the forest hydrological cycle is complex and usually requires a combination of field monitoring and modelling approaches (Weiler and McDonnell, 2004; National Research Council, 2008). Models are important tools for testing hypotheses, understanding hydrological processes and synthesizing experimental data...

The physiology of stress and effects on immune health in ruminants

USDA-ARS?s Scientific Manuscript database

As researchers have continued to explore the complex interactions among stress and production parameters such as growth, feed efficiency, and health, multidisciplinary efforts have emerged leading to a greater understanding of homeostatic regulation. The immune system can be regulated by several dif...

UNDERSTANDING PLANT-SOIL RELATIONSHIPS USING CONTROLLED ENVIRONMENT FACILITIES

EPA Science Inventory

Although soil is a component of terrestrial ecosystems, it is comprised of a complex web of interacting organisms, and therefore, can be considered itself as an ecosystem. Soil microflora and fauna derive energy from plants and plant residues and serve important functions in mai...

The Potentiality of Gaming-Simulation in Architecture.

ERIC Educational Resources Information Center

May, Hayden Barkley

1979-01-01

Gaming-simulation in professional practice, education, and research is discussed. Simulation assists in exploring and resolving incongruent values and interests of clients, users, and architects; conveys complex interactive systems students are trying to understand; and elicits responses to alternative actions and contributes to theory development…

The Social Organization of Schooling

ERIC Educational Resources Information Center

Hedges, Larry V., Ed.; Schneider, Barbara, Ed.

2005-01-01

Schools are complex social settings where students, teachers, administrators, and parents interact to shape a child's educational experience. Any effort to improve educational outcomes for America's children requires a dynamic understanding of the environments in which children learn. In "The Social Organization of Schooling", editors Larry Hedges…

Compatibility between Legumes and Rhizobia for the Establishment of a Successful Nitrogen-Fixing Symbiosis

PubMed Central

Clúa, Joaquín; Roda, Carla

2018-01-01

The root nodule symbiosis established between legumes and rhizobia is an exquisite biological interaction responsible for fixing a significant amount of nitrogen in terrestrial ecosystems. The success of this interaction depends on the recognition of the right partner by the plant within the richest microbial ecosystems on Earth, the soil. Recent metagenomic studies of the soil biome have revealed its complexity, which includes microorganisms that affect plant fitness and growth in a beneficial, harmful, or neutral manner. In this complex scenario, understanding the molecular mechanisms by which legumes recognize and discriminate rhizobia from pathogens, but also between distinct rhizobia species and strains that differ in their symbiotic performance, is a considerable challenge. In this work, we will review how plants are able to recognize and select symbiotic partners from a vast diversity of surrounding bacteria. We will also analyze recent advances that contribute to understand changes in plant gene expression associated with the outcome of the symbiotic interaction. These aspects of nitrogen-fixing symbiosis should contribute to translate the knowledge generated in basic laboratory research into biotechnological advances to improve the efficiency of the nitrogen-fixing symbiosis in agronomic systems. PMID:29495432

The microbiome at the pulmonary alveolar niche and its role in Mycobacterium tuberculosis infection.

PubMed

Adami, Alexander J; Cervantes, Jorge L

2015-12-01

Advances in next generation sequencing (NGS) technology have provided the tools to comprehensively and accurately characterize the microbial community in the respiratory tract in health and disease. The presence of commensal and pathogenic bacteria has been found to have important effects on the lung immune system. Until relatively recently, the lung has received less attention compared to other body sites in terms of microbiome characterization, and its study carries special technological difficulties related to obtaining reliable samples as compared to other body niches. Additionally, the complexity of the alveolar immune system, and its interactions with the lung microbiome, are only just beginning to be understood. Amidst this complexity sits Mycobacterium tuberculosis (Mtb), one of humanity's oldest nemeses and a significant public health concern, with millions of individuals infected with Mtb worldwide. The intricate interactions between Mtb, the lung microbiome, and the alveolar immune system are beginning to be understood, and it is increasingly apparent that improved treatment of Mtb will only come through deep understanding of the interplay between these three forces. In this review, we summarize our current understanding of the lung microbiome, alveolar immunity, and the interaction of each with Mtb. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multiparametric Imaging of Organ System Interfaces

PubMed Central

Vandoorne, Katrien; Nahrendorf, Matthias

2017-01-01

Cardiovascular diseases are a consequence of genetic and environmental risk factors that together generate arterial wall and cardiac pathologies. Blood vessels connect multiple systems throughout the entire body and allow organs to interact via circulating messengers. These same interactions facilitate nervous and metabolic system influence on cardiovascular health. Multiparametric imaging offers the opportunity to study these interfacing systems’ distinct processes, to quantify their interactions and to explore how these contribute to cardiovascular disease. Noninvasive multiparametric imaging techniques are emerging tools that can further our understanding of this complex and dynamic interplay. PET/MRI and multichannel optical imaging are particularly promising because they can simultaneously sample multiple biomarkers. Preclinical multiparametric diagnostics could help discover clinically relevant biomarker combinations pivotal for understanding cardiovascular disease. Interfacing systems important to cardiovascular disease include the immune, nervous and hematopoietic systems. These systems connect with ‘classical’ cardiovascular organs, like the heart and vasculature, and with the brain. The dynamic interplay between these systems and organs enables processes such as hemostasis, inflammation, angiogenesis, matrix remodeling, metabolism and fibrosis. As the opportunities provided by imaging expand, mapping interconnected systems will help us decipher the complexity of cardiovascular disease and monitor novel therapeutic strategies. PMID:28360260

A taxonomy of visualization tasks for the analysis of biological pathway data.

PubMed

Murray, Paul; McGee, Fintan; Forbes, Angus G

2017-02-15

Understanding complicated networks of interactions and chemical components is essential to solving contemporary problems in modern biology, especially in domains such as cancer and systems research. In these domains, biological pathway data is used to represent chains of interactions that occur within a given biological process. Visual representations can help researchers understand, interact with, and reason about these complex pathways in a number of ways. At the same time, these datasets offer unique challenges for visualization, due to their complexity and heterogeneity. Here, we present taxonomy of tasks that are regularly performed by researchers who work with biological pathway data. The generation of these tasks was done in conjunction with interviews with several domain experts in biology. These tasks require further classification than is provided by existing taxonomies. We also examine existing visualization techniques that support each task, and we discuss gaps in the existing visualization space revealed by our taxonomy. Our taxonomy is designed to support the development and design of future biological pathway visualization applications. We conclude by suggesting future research directions based on our taxonomy and motivated by the comments received by our domain experts.

Experimental Models to Study the Role of Microbes in Host-Parasite Interactions.

PubMed

Hahn, Megan A; Dheilly, Nolwenn M

2016-01-01

Until recently, parasitic infections have been primarily studied as interactions between the parasite and the host, leaving out crucial players: microbes. The recent realization that microbes play key roles in the biology of all living organisms is not only challenging our understanding of host-parasite evolution, but it also provides new clues to develop new therapies and remediation strategies. In this paper we provide a review of promising and advanced experimental organismal systems to examine the dynamic of host-parasite-microbe interactions. We address the benefits of developing new experimental models appropriate to this new research area and identify systems that offer the best promises considering the nature of the interactions among hosts, parasites, and microbes. Based on these systems, we identify key criteria for selecting experimental models to elucidate the fundamental principles of these complex webs of interactions. It appears that no model is ideal and that complementary studies should be performed on different systems in order to understand the driving roles of microbes in host and parasite evolution.

Nanodiamond decorated liposomes as highly biocompatible delivery vehicles and a comparison with carbon nanotubes and graphene oxide.

PubMed

Wang, Feng; Liu, Juewen

2013-12-21

Studying interactions between nano-carbons and lipid membranes is important for multiplexed drug delivery, device fabrication and for understanding toxicity. Herein, we report that nanodiamond (ND, sp(3) carbon) forms a complex with highly biocompatible zwitterionic liposomes based on hydrogen bonding, which is confirmed by pH-dependent and urea-dependent assays. Despite such weak interaction, the complex is highly stable. Comparisons were made with two sp(2) carbons: nanoscale graphene oxide (NGO) and carbon nanotubes (CNTs), where CNT adsorption is the weakest. Adsorption of the nano-carbons does not induce liposome leakage or affect lipid phase transition temperature. Therefore, the potential toxicity of nano-carbons is unlikely to be related to direct membrane damage. ND facilitates cellular uptake of liposomes and co-delivery of negatively charged calcein and positively charged doxorubicin has been demonstrated. ND has the lowest toxicity, while CNTs and NGO are slightly more toxic. The effect of introducing fusogenic lipids and cholesterol was further studied to understand the effect of lipid formulation.

Integrating Epigenomics into the Understanding of Biomedical Insight.

PubMed

Han, Yixing; He, Ximiao

2016-01-01

Epigenetics is one of the most rapidly expanding fields in biomedical research, and the popularity of the high-throughput next-generation sequencing (NGS) highlights the accelerating speed of epigenomics discovery over the past decade. Epigenetics studies the heritable phenotypes resulting from chromatin changes but without alteration on DNA sequence. Epigenetic factors and their interactive network regulate almost all of the fundamental biological procedures, and incorrect epigenetic information may lead to complex diseases. A comprehensive understanding of epigenetic mechanisms, their interactions, and alterations in health and diseases genome widely has become a priority in biological research. Bioinformatics is expected to make a remarkable contribution for this purpose, especially in processing and interpreting the large-scale NGS datasets. In this review, we introduce the epigenetics pioneering achievements in health status and complex diseases; next, we give a systematic review of the epigenomics data generation, summarize public resources and integrative analysis approaches, and finally outline the challenges and future directions in computational epigenomics.

Integrating Epigenomics into the Understanding of Biomedical Insight

PubMed Central

Han, Yixing; He, Ximiao

2016-01-01

Epigenetics is one of the most rapidly expanding fields in biomedical research, and the popularity of the high-throughput next-generation sequencing (NGS) highlights the accelerating speed of epigenomics discovery over the past decade. Epigenetics studies the heritable phenotypes resulting from chromatin changes but without alteration on DNA sequence. Epigenetic factors and their interactive network regulate almost all of the fundamental biological procedures, and incorrect epigenetic information may lead to complex diseases. A comprehensive understanding of epigenetic mechanisms, their interactions, and alterations in health and diseases genome widely has become a priority in biological research. Bioinformatics is expected to make a remarkable contribution for this purpose, especially in processing and interpreting the large-scale NGS datasets. In this review, we introduce the epigenetics pioneering achievements in health status and complex diseases; next, we give a systematic review of the epigenomics data generation, summarize public resources and integrative analysis approaches, and finally outline the challenges and future directions in computational epigenomics. PMID:27980397

New insights into saline water evaporation from porous media: Complex interaction between evaporation rates, precipitation, and surface temperature

NASA Astrophysics Data System (ADS)

Shokri-Kuehni, Salomé M. S.; Vetter, Thomas; Webb, Colin; Shokri, Nima

2017-06-01

Understanding salt transport and deposition patterns during evaporation from porous media is important in many engineering and hydrological processes such as soil salinization, ecosystem functioning, and land-atmosphere interaction. As evaporation proceeds, salt concentration increases until it exceeds solubility limits, locally, and crystals precipitate. The interplay between transport processes, crystallization, and evaporation influences where crystallization occurs. During early stages, the precipitated salt creates an evolving porous structure affecting the evaporation kinetics. We conducted a comprehensive series of experiments to investigate how the salt concentration and precipitation influence evaporation dynamics. Our results illustrate the contribution of the evolving salt crust to the evaporative mass losses. High-resolution thermal imaging enabled us to investigate the complex temperature dynamics at the surface of precipitated salt, providing further confirmation of salt crust contribution to the evaporation. We identify different phases of saline water evaporation from porous media with the corresponding dominant mechanisms in each phase and extend the physical understanding of such processes.

New approaches in agent-based modeling of complex financial systems

NASA Astrophysics Data System (ADS)

Chen, Ting-Ting; Zheng, Bo; Li, Yan; Jiang, Xiong-Fei

2017-12-01

Agent-based modeling is a powerful simulation technique to understand the collective behavior and microscopic interaction in complex financial systems. Recently, the concept for determining the key parameters of agent-based models from empirical data instead of setting them artificially was suggested. We first review several agent-based models and the new approaches to determine the key model parameters from historical market data. Based on the agents' behaviors with heterogeneous personal preferences and interactions, these models are successful in explaining the microscopic origination of the temporal and spatial correlations of financial markets. We then present a novel paradigm combining big-data analysis with agent-based modeling. Specifically, from internet query and stock market data, we extract the information driving forces and develop an agent-based model to simulate the dynamic behaviors of complex financial systems.

Corolla Is a Novel Protein That Contributes to the Architecture of the Synaptonemal Complex of Drosophila

PubMed Central

Collins, Kimberly A.; Unruh, Jay R.; Slaughter, Brian D.; Yu, Zulin; Lake, Cathleen M.; Nielsen, Rachel J.; Box, Kimberly S.; Miller, Danny E.; Blumenstiel, Justin P.; Perera, Anoja G.; Malanowski, Kathryn E.; Hawley, R. Scott

2014-01-01

In most organisms the synaptonemal complex (SC) connects paired homologs along their entire length during much of meiotic prophase. To better understand the structure of the SC, we aim to identify its components and to determine how each of these components contributes to SC function. Here, we report the identification of a novel SC component in Drosophila melanogaster female oocytes, which we have named Corolla. Using structured illumination microscopy, we demonstrate that Corolla is a component of the central region of the SC. Consistent with its localization, we show by yeast two-hybrid analysis that Corolla strongly interacts with Cona, a central element protein, demonstrating the first direct interaction between two inner-synaptonemal complex proteins in Drosophila. These observations help provide a more complete model of SC structure and function in Drosophila females. PMID:24913682

Symmetry blockade and its breakdown in energy equipartition of square graphene resonators

NASA Astrophysics Data System (ADS)

Wang, Yisen; Zhu, Zhigang; Zhang, Yong; Huang, Liang

2018-03-01

The interaction between flexural modes due to nonlinear potentials is critical to heat conductivity and mechanical vibration of two dimensional materials such as graphene. Much effort has been devoted to understanding the underlying mechanism. In this paper, we examine solely the out-of-plane flexural modes and identify their energy flow pathway during the equipartition process. In particular, the modes are grouped into four classes by their distinct symmetries. The couplings are significantly larger within a class than between classes, forming symmetry blockades. As a result, the energy first flows to the modes in the same symmetry class. Breakdown of the symmetry blockade, i.e., inter-class energy flow, starts when the displacement profile becomes complex and the inter-class couplings bear nonneglectable values. The equipartition time follows the stretched exponential law and survives in the thermodynamic limit. These results bring fundamental understandings to the Fermi-Pasta-Ulam problem in two dimensional systems with complex potentials and reveal clearly the physical picture of dynamical interactions between the flexural modes, which will be crucial to the understanding of their contribution in high thermal conductivity and mechanism of energy dissipation that may intrinsically limit the quality factor of the resonator.

Taking Systems Medicine to Heart.

PubMed

Trachana, Kalliopi; Bargaje, Rhishikesh; Glusman, Gustavo; Price, Nathan D; Huang, Sui; Hood, Leroy E

2018-04-27

Systems medicine is a holistic approach to deciphering the complexity of human physiology in health and disease. In essence, a living body is constituted of networks of dynamically interacting units (molecules, cells, organs, etc) that underlie its collective functions. Declining resilience because of aging and other chronic environmental exposures drives the system to transition from a health state to a disease state; these transitions, triggered by acute perturbations or chronic disturbance, manifest as qualitative shifts in the interactions and dynamics of the disease-perturbed networks. Understanding health-to-disease transitions poses a high-dimensional nonlinear reconstruction problem that requires deep understanding of biology and innovation in study design, technology, and data analysis. With a focus on the principles of systems medicine, this Review discusses approaches for deciphering this biological complexity from a novel perspective, namely, understanding how disease-perturbed networks function; their study provides insights into fundamental disease mechanisms. The immediate goals for systems medicine are to identify early transitions to cardiovascular (and other chronic) diseases and to accelerate the translation of new preventive, diagnostic, or therapeutic targets into clinical practice, a critical step in the development of personalized, predictive, preventive, and participatory (P4) medicine. © 2018 American Heart Association, Inc.

Applying principles from the game theory to acute stroke care: Learning from the prisoner's dilemma, stag-hunt, and other strategies.

PubMed

Saposnik, Gustavo; Johnston, S Claiborne

2016-04-01

Acute stroke care represents a challenge for decision makers. Decisions based on erroneous assessments may generate false expectations of patients and their family members, and potentially inappropriate medical advice. Game theory is the analysis of interactions between individuals to study how conflict and cooperation affect our decisions. We reviewed principles of game theory that could be applied to medical decisions under uncertainty. Medical decisions in acute stroke care are usually made under constrains: short period of time, with imperfect clinical information, limit understanding about patients and families' values and beliefs. Game theory brings some strategies to help us manage complex medical situations under uncertainty. For example, it offers a different perspective by encouraging the consideration of different alternatives through the understanding of patients' preferences and the careful evaluation of cognitive distortions when applying 'real-world' data. The stag-hunt game teaches us the importance of trust to strength cooperation for a successful patient-physician interaction that is beyond a good or poor clinical outcome. The application of game theory to stroke care may improve our understanding of complex medical situations and help clinicians make practical decisions under uncertainty. © 2016 World Stroke Organization.

What is microbial community ecology?

PubMed

Konopka, Allan

2009-11-01

The activities of complex communities of microbes affect biogeochemical transformations in natural, managed and engineered ecosystems. Meaningfully defining what constitutes a community of interacting microbial populations is not trivial, but is important for rigorous progress in the field. Important elements of research in microbial community ecology include the analysis of functional pathways for nutrient resource and energy flows, mechanistic understanding of interactions between microbial populations and their environment, and the emergent properties of the complex community. Some emergent properties mirror those analyzed by community ecologists who study plants and animals: biological diversity, functional redundancy and system stability. However, because microbes possess mechanisms for the horizontal transfer of genetic information, the metagenome may also be considered as a community property.

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

Konopka, Allan

The activities of complex communities of microbes affect biogeochemical transformations in natural, managed and engineered ecosystems. Meaningfully defining what constitutes a community of interacting microbial populations is not trivial, but is important for rigorous progress in the field. Important elements of research in microbial community ecology include the analysis of functional pathways for nutrient resource and energy flows, mechanistic understanding of interactions between microbial populations and their environment, and the emergent properties of the complex community. Some emergent properties mirror those analyzed by community ecologists who study plants and animals: biological diversity, functional redundancy and system stability. However, because microbesmore » possess mechanisms for the horizontal transfer of genetic information, the metagenome may also be considered a community property.« less

Life history determines genetic structure and evolutionary potential of host–parasite interactions

PubMed Central

Barrett, Luke G.; Thrall, Peter H.; Burdon, Jeremy J.; Linde, Celeste C.

2009-01-01

Measures of population genetic structure and diversity of disease-causing organisms are commonly used to draw inferences regarding their evolutionary history and potential to generate new variation in traits that determine interactions with their hosts. Parasite species exhibit a range of population structures and life-history strategies, including different transmission modes, life-cycle complexity, off-host survival mechanisms and dispersal ability. These are important determinants of the frequency and predictability of interactions with host species. Yet the complex causal relationships between spatial structure, life history and the evolutionary dynamics of parasite populations are not well understood. We demonstrate that a clear picture of the evolutionary potential of parasitic organisms and their demographic and evolutionary histories can only come from understanding the role of life history and spatial structure in influencing population dynamics and epidemiological patterns. PMID:18947899

Life history determines genetic structure and evolutionary potential of host-parasite interactions.

PubMed

Barrett, Luke G; Thrall, Peter H; Burdon, Jeremy J; Linde, Celeste C

2008-12-01

Measures of population genetic structure and diversity of disease-causing organisms are commonly used to draw inferences regarding their evolutionary history and potential to generate new variation in traits that determine interactions with their hosts. Parasite species exhibit a range of population structures and life-history strategies, including different transmission modes, life-cycle complexity, off-host survival mechanisms and dispersal ability. These are important determinants of the frequency and predictability of interactions with host species. Yet the complex causal relationships between spatial structure, life history and the evolutionary dynamics of parasite populations are not well understood. We demonstrate that a clear picture of the evolutionary potential of parasitic organisms and their demographic and evolutionary histories can only come from understanding the role of life history and spatial structure in influencing population dynamics and epidemiological patterns.

A divalent interaction between HPS1 and HPS4 is required for the formation of the biogenesis of lysosome-related organelle complex-3 (BLOC-3).

PubMed

Carmona-Rivera, Carmelo; Simeonov, Dimitre R; Cardillo, Nicholas D; Gahl, William A; Cadilla, Carmen L

2013-03-01

Hermansky-Pudlak syndrome (HPS) is a group of rare autosomal recessive disorders characterized by oculocutaneous albinism, a bleeding tendency, and sporadic pulmonary fibrosis, granulomatous colitis or infections. Nine HPS-causing genes have been identified in humans. HPS-1 is the most severe subtype with a prevalence of ~1/1800 in northwest Puerto Rico due to a founder mutation in the HPS1 gene. Mutations in HPS genes affect the biogenesis of lysosome-related organelles such as melanosomes in melanocytes and platelet dense granules. Two of these genes (HPS1 and HPS4) encode the HPS1 and HPS4 proteins, which assemble to form a complex known as Biogenesis of Lysosome-related Organelle Complex 3 (BLOC-3). We report the identification of the interacting regions in HPS1 and HPS4 required for the formation of this complex. Two regions in HPS1, spanning amino acids 1-249 and 506-700 are required for binding to HPS4; the middle portion of HPS1 (residues 250-505) is not required for this interaction. Further interaction studies showed that the N-termini of HPS1 and HPS4 interact with each other and that a discrete region of HPS4 (residues 340-528) interacts with both the N- and C-termini of the HPS1 protein. Several missense mutations found in HPS-1 patients did not affect interaction with HPS4, but some mutations involving regions interacting with HPS4 caused instability of HPS1. These observations extend our understanding of BLOC-3 assembly and represent an important first step in the identification of domains responsible for the biogenesis of lysosome-related organelles. Copyright © 2012 Elsevier B.V. All rights reserved.

Linking market interaction intensity of 3D Ising type financial model with market volatility

NASA Astrophysics Data System (ADS)

Fang, Wen; Ke, Jinchuan; Wang, Jun; Feng, Ling

2016-11-01

Microscopic interaction models in physics have been used to investigate the complex phenomena of economic systems. The simple interactions involved can lead to complex behaviors and help the understanding of mechanisms in the financial market at a systemic level. This article aims to develop a financial time series model through 3D (three-dimensional) Ising dynamic system which is widely used as an interacting spins model to explain the ferromagnetism in physics. Through Monte Carlo simulations of the financial model and numerical analysis for both the simulation return time series and historical return data of Hushen 300 (HS300) index in Chinese stock market, we show that despite its simplicity, this model displays stylized facts similar to that seen in real financial market. We demonstrate a possible underlying link between volatility fluctuations of real stock market and the change in interaction strengths of market participants in the financial model. In particular, our stochastic interaction strength in our model demonstrates that the real market may be consistently operating near the critical point of the system.

Synergistic Interactions of Sugars/Polyols and Monovalent Salts with Phospholipids Depend upon Sugar/Polyol Complexity and Anion Identity.

PubMed

Clark, Ginevra A; Henderson, J Michael; Heffern, Charles; Akgün, Bülent; Majewski, Jaroslaw; Lee, Ka Yee C

2015-11-24

We found that interactions of dipalmitoylphosphatidylcholine (DPPC) lipid monolayers with sugars are influenced by addition of NaCl. This work is of general importance in understanding how sugar-lipid-salt interactions impact biological systems. Using Langmuir isothermal compressions, fluorescence microscopy, atomic force microscopy, and neutron reflectometry, we examined DPPC monolayers upon addition of sugars/polyols and/or monovalent salts. Sugar-lipid interactions in the presence of NaCl increased with increasing complexity of the sugar/polyol in the order glycerol ≪ glucose < trehalose. When the anion was altered in the series NaF, NaCl, and NaBr, only minor differences were observed. When comparing LiCl, NaCl, and KCl, sodium chloride had the greatest influence on glucose and trehalose interactions with DPPC. We propose that heterogeneity created by cation binding allows for sugars to bind the lipid headgroups. While cation binding increases in the order K(+) < Na(+) < Li(+), lithium ions may also compete with glucose for binding sites. Thus, both cooperative and competitive factors contribute to the overall influence of salts on sugar-lipid interactions.

Structure of the Mtb CarD/RNAP β-lobes complex reveals the molecular basis of interaction and presents a distinct DNA-binding domain for Mtb CarD.

PubMed

Gulten, Gulcin; Sacchettini, James C

2013-10-08

CarD from Mycobacterium tuberculosis (Mtb) is an essential protein shown to be involved in stringent response through downregulation of rRNA and ribosomal protein genes. CarD interacts with the β-subunit of RNAP and this interaction is vital for Mtb's survival during the persistent infection state. We have determined the crystal structure of CarD in complex with the RNAP β-subunit β1 and β2 domains at 2.1 Å resolution. The structure reveals the molecular basis of CarD/RNAP interaction, providing a basis to further our understanding of RNAP regulation by CarD. The structural fold of the CarD N-terminal domain is conserved in RNAP interacting proteins such as TRCF-RID and CdnL, and displays similar interactions to the predicted homology model based on the TRCF/RNAP β1 structure. Interestingly, the structure of the C-terminal domain, which is required for complete CarD function in vivo, represents a distinct DNA-binding fold. Copyright © 2013 Elsevier Ltd. All rights reserved.

Metal nanoparticle-graphene oxide composites: Photophysical properties and sensing applications

NASA Astrophysics Data System (ADS)

Murphy, Sean J.

Composite nanomaterials allow for attractive properties of multiple functional components to be combined. Fundamental understanding of the interaction between different nanomaterials, their surroundings, and nearby molecular species is pertinent for implementation into devices. Metal nanoparticles have been used for their optical properties in many applications including stained glass, cancer therapy, solar steam generation, surface enhanced Raman spectroscopy (SERS), and catalysis. Carbon-based nanomaterials such as graphene and carbon nanotubes show potential for a wide variety of applications including solar energy harvesting, chemical sensors, and electronics. Combining useful and in some cases new properties of composite nanomaterials offers exciting opportunities in fundamental science and device development. In this dissertation, I aim to address understanding photoinduced interaction between porphyrin and silver nanoparticles, inter-sheet interaction between stacked graphene oxide (GO) sheets in thin films, complexation of reduced GO with Raman active target molecule in SERS applications, and efficacy of graphene-metal nanoparticle composites for sensing applications. Molecule-metal nanoparticle composite material made up of photoactive porphyrin and silver nanoparticles was studied using various spectroscopic tools. UV-visible absorption and surface enhanced Raman spectroscopic results suggest formation of a charge-transfer complex for porphyrin-silver nanoparticle composite. Ultrafast transient absorption and fluorescence upconversion spectroscopies further corroborate electronic interaction by providing evidence for excited state electron transfer between porphyrin and silver nanoparticles. Understanding electronic interaction between adsorbed photoactive molecules and metal nanoparticles may be of use for applications in photocatalysis or light-energy harvesting. Graphene oxide (GO) thin films have been prepared and studied using transient absorption microscopy (TAM). Transient absorption microscopy correlated with atomic force microscope allows for the morphological properties of GO thin film to be related to optical properties, namely dynamics of photoexcited carriers in GO. Results suggest short-timescale (ps -- ˜1 ns) dynamics of charge carriers in GO are affected very little by interaction with the glass substrate on which GO is placed. Also, the stack thickness or number of stacked GO sheets does not play a large role in the short-timescale dynamics of GO charge carriers. GO or reduced GO (RGO)-silver nanoparticles composites were produced using different methods: (1) chemical reduction of silver ion precursor and (2) photocatalytic reduction of GO and silver ion using TiO2 nanoparticles. Optical and morphological properties of composites were studied using spectroscopy and electron microscopy revealing a degree of control in metal nanoparticle growth and loading on the surface of RGO. Nanocomposites were shown to be capable of complexing with or adsorbing target molecular species. Complexation and adsorption are corroborated with demonstration that the composite nanomaterials act as effective SERRS sensors taking advantage of localized surface plasmon resonance of metal nanoparticles and the ability of RGO to interact with molecular and ionic species.

Exploring the Human-Nipah Virus Protein-Protein Interactome

PubMed Central

Vera-Velasco, Natalia M.; Mingarro, Ismael

2017-01-01

ABSTRACT Nipah virus is an emerging, highly pathogenic, zoonotic virus of the Paramyxoviridae family. Human transmission occurs by close contact with infected animals, the consumption of contaminated food, or, occasionally, via other infected individuals. Currently, we lack therapeutic or prophylactic treatments for Nipah virus. To develop these agents we must now improve our understanding of the host-virus interactions that underpin a productive infection. This aim led us to perform the present work, in which we identified 101 human-Nipah virus protein-protein interactions (PPIs), most of which (88) are novel. This data set provides a comprehensive view of the host complexes that are manipulated by viral proteins. Host targets include the PRP19 complex and the microRNA (miRNA) processing machinery. Furthermore, we explored the biologic consequences of the interaction with the PRP19 complex and found that the Nipah virus W protein is capable of altering p53 control and gene expression. We anticipate that these data will help in guiding the development of novel interventional strategies to counter this emerging viral threat. IMPORTANCE Nipah virus is a recently discovered virus that infects a wide range of mammals, including humans. Since its discovery there have been yearly outbreaks, and in some of them the mortality rate has reached 100% of the confirmed cases. However, the study of Nipah virus has been largely neglected, and currently we lack treatments for this infection. To develop these agents we must now improve our understanding of the host-virus interactions that underpin a productive infection. In the present work, we identified 101 human-Nipah virus protein-protein interactions using an affinity purification approach coupled with mass spectrometry. Additionally, we explored the cellular consequences of some of these interactions. Globally, this data set offers a comprehensive and detailed view of the host machinery's contribution to the Nipah virus's life cycle. Furthermore, our data present a large number of putative drug targets that could be exploited for the treatment of this infection. PMID:28904190

Exploring the Human-Nipah Virus Protein-Protein Interactome.

PubMed

Martinez-Gil, Luis; Vera-Velasco, Natalia M; Mingarro, Ismael

2017-12-01

Nipah virus is an emerging, highly pathogenic, zoonotic virus of the Paramyxoviridae family. Human transmission occurs by close contact with infected animals, the consumption of contaminated food, or, occasionally, via other infected individuals. Currently, we lack therapeutic or prophylactic treatments for Nipah virus. To develop these agents we must now improve our understanding of the host-virus interactions that underpin a productive infection. This aim led us to perform the present work, in which we identified 101 human-Nipah virus protein-protein interactions (PPIs), most of which (88) are novel. This data set provides a comprehensive view of the host complexes that are manipulated by viral proteins. Host targets include the PRP19 complex and the microRNA (miRNA) processing machinery. Furthermore, we explored the biologic consequences of the interaction with the PRP19 complex and found that the Nipah virus W protein is capable of altering p53 control and gene expression. We anticipate that these data will help in guiding the development of novel interventional strategies to counter this emerging viral threat. IMPORTANCE Nipah virus is a recently discovered virus that infects a wide range of mammals, including humans. Since its discovery there have been yearly outbreaks, and in some of them the mortality rate has reached 100% of the confirmed cases. However, the study of Nipah virus has been largely neglected, and currently we lack treatments for this infection. To develop these agents we must now improve our understanding of the host-virus interactions that underpin a productive infection. In the present work, we identified 101 human-Nipah virus protein-protein interactions using an affinity purification approach coupled with mass spectrometry. Additionally, we explored the cellular consequences of some of these interactions. Globally, this data set offers a comprehensive and detailed view of the host machinery's contribution to the Nipah virus's life cycle. Furthermore, our data present a large number of putative drug targets that could be exploited for the treatment of this infection. Copyright © 2017 American Society for Microbiology.

An anti-DNA antibody prefers damaged dsDNA over native.

PubMed

Akberova, N I; Zhmurov, A A; Nevzorova, T A; Litvinov, R I

2017-01-01

DNA-protein interactions, including DNA-antibody complexes, have both fundamental and practical significance. In particular, antibodies against double-stranded DNA play an important role in the pathogenesis of autoimmune diseases. Elucidation of structural mechanisms of an antigen recognition and interaction of anti-DNA antibodies provides a basis for understanding the role of DNA-containing immune complexes in human pathologies and for new treatments. Here we used Molecular Dynamic simulations of bimolecular complexes of a segment of dsDNA with a monoclonal anti-DNA antibody's Fab-fragment to obtain detailed structural and physical characteristics of the dynamic intermolecular interactions. Using a computationally modified crystal structure of a Fab-DNA complex (PDB: 3VW3), we studied in silico equilibrium Molecular Dynamics of the Fab-fragment associated with two homologous dsDNA fragments, containing or not containing dimerized thymine, a product of DNA photodamage. The Fab-fragment interactions with the thymine dimer-containing DNA was thermodynamically more stable than with the native DNA. The amino acid residues constituting a paratope and the complementary nucleotide epitopes for both Fab-DNA constructs were identified. Stacking and electrostatic interactions were shown to play the main role in the antibody-dsDNA contacts, while hydrogen bonds were less significant. The aggregate of data show that the chemically modified dsDNA (containing a covalent thymine dimer) has a higher affinity toward the antibody and forms a stronger immune complex. These findings provide a mechanistic insight into formation and properties of the pathogenic anti-DNA antibodies in autoimmune diseases, such as systemic lupus erythematosus, associated with skin photosensibilization and DNA photodamage.

In Vitro Identification of Histatin 5 Salivary Complexes

PubMed Central

Moffa, Eduardo B.; Machado, Maria A. A. M.; Mussi, Maria C. M.; Xiao, Yizhi; Garrido, Saulo S.; Giampaolo, Eunice T.; Siqueira, Walter L.

2015-01-01

With recent progress in the analysis of the salivary proteome, the number of salivary proteins identified has increased dramatically. However, the physiological functions of many of the newly discovered proteins remain unclear. Closely related to the study of a protein’s function is the identification of its interaction partners. Although in saliva some proteins may act primarily as single monomeric units, a significant percentage of all salivary proteins, if not the majority, appear to act in complexes with partners to execute their diverse functions. Coimmunoprecipitation (Co-IP) and pull-down assays were used to identify the heterotypic complexes between histatin 5, a potent natural antifungal protein, and other salivary proteins in saliva. Classical protein–protein interaction methods in combination with high-throughput mass spectrometric techniques were carried out. Co-IP using protein G magnetic Sepharose TM beads suspension was able to capture salivary complexes formed between histatin 5 and its salivary protein partners. Pull-down assay was used to confirm histatin 5 protein partners. A total of 52 different proteins were identified to interact with histatin 5. The present study used proteomic approaches in conjunction with classical biochemical methods to investigate protein–protein interaction in human saliva. Our study demonstrated that when histatin 5 is complexed with salivary amylase, one of the 52 proteins identified as a histatin 5 partner, the antifungal activity of histatin 5 is reduced. We expected that our proteomic approach could serve as a basis for future studies on the mechanism and structural-characterization of those salivary protein interactions to understand their clinical significance. PMID:26544073

Dynamical minimalism: why less is more in psychology.

PubMed

Nowak, Andrzej

2004-01-01

The principle of parsimony, embraced in all areas of science, states that simple explanations are preferable to complex explanations in theory construction. Parsimony, however, can necessitate a trade-off with depth and richness in understanding. The approach of dynamical minimalism avoids this trade-off. The goal of this approach is to identify the simplest mechanisms and fewest variables capable of producing the phenomenon in question. A dynamical model in which change is produced by simple rules repetitively interacting with each other can exhibit unexpected and complex properties. It is thus possible to explain complex psychological and social phenomena with very simple models if these models are dynamic. In dynamical minimalist theories, then, the principle of parsimony can be followed without sacrificing depth in understanding. Computer simulations have proven especially useful for investigating the emergent properties of simple models.

Precursors to language development in typically and atypically developing infants and toddlers: the importance of embracing complexity.

PubMed

D'Souza, Dean; D'Souza, Hana; Karmiloff-Smith, Annette

2017-05-01

In order to understand how language abilities emerge in typically and atypically developing infants and toddlers, it is important to embrace complexity in development. In this paper, we describe evidence that early language development is an experience-dependent process, shaped by diverse, interconnected, interdependent developmental mechanisms, processes, and abilities (e.g. statistical learning, sampling, functional specialization, visual attention, social interaction, motor ability). We also present evidence from our studies on neurodevelopmental disorders (e.g. Down syndrome, fragile X syndrome, Williams syndrome) that variations in these factors significantly contribute to language delay. Finally, we discuss how embracing complexity, which involves integrating data from different domains and levels of description across developmental time, may lead to a better understanding of language development and, critically, lead to more effective interventions for cases when language develops atypically.

Identifying Dynamic Protein Complexes Based on Gene Expression Profiles and PPI Networks

PubMed Central

Li, Min; Chen, Weijie; Wang, Jianxin; Pan, Yi

2014-01-01

Identification of protein complexes from protein-protein interaction networks has become a key problem for understanding cellular life in postgenomic era. Many computational methods have been proposed for identifying protein complexes. Up to now, the existing computational methods are mostly applied on static PPI networks. However, proteins and their interactions are dynamic in reality. Identifying dynamic protein complexes is more meaningful and challenging. In this paper, a novel algorithm, named DPC, is proposed to identify dynamic protein complexes by integrating PPI data and gene expression profiles. According to Core-Attachment assumption, these proteins which are always active in the molecular cycle are regarded as core proteins. The protein-complex cores are identified from these always active proteins by detecting dense subgraphs. Final protein complexes are extended from the protein-complex cores by adding attachments based on a topological character of “closeness” and dynamic meaning. The protein complexes produced by our algorithm DPC contain two parts: static core expressed in all the molecular cycle and dynamic attachments short-lived. The proposed algorithm DPC was applied on the data of Saccharomyces cerevisiae and the experimental results show that DPC outperforms CMC, MCL, SPICi, HC-PIN, COACH, and Core-Attachment based on the validation of matching with known complexes and hF-measures. PMID:24963481

Pedagogy of complex relationality exploring complexity theory, neuro-phenomenology, and attentiveness for education

NASA Astrophysics Data System (ADS)

Khattar, Randa

What do the new sciences of complex relationality offer education? This work draws on complexity theory, neurological understandings of biology and phenomenology, and attentiveness to study what the new sciences might offer education and the possibilities of a pedagogical understanding of embodied knowing. Complexity theory provides understandings of local-global relationality, self-organization, far-from-equilibrium conditions, and emergent dynamics that are important for describing pedagogical relationality. In itself, however, complexity theory is lacking an attention to issues of embodiment that respond directly to an ethical understanding of relationality. Phenomenology provides important views on the human experience of perception, for example, Merleau-Ponty's, whose research opens up possibilities for embodiment and attentiveness. At the level of pedagogical practice, I will pose, following biologists Humberto Maturana and Francisco Varela's autopoietic self-making understanding of life, that attentiveness perspectives, which have been largely absent from western pedagogical theory and practice, are crucial to promoting embodied knowing for education. Maturana and Varela's autopoietic perspective offers an embodied understanding of living---and therefore education---which opens up necessary attentive spaces to listen to one another in non judgmental awareness in the present moment of experience. I offer insights into a relationally complex conception of education drawing on this biological and autopoietically-grounded framework. These insights are framed in the context of five clusters of relations: (1) emergence, far-from-equilibrium, and local-global relationality; (2) autopoietic autonomy, structural determination and sensory-motor coupling; (3) triggering perturbations, structural plasticity, and autopoietic organization; (4) knowing as adequate action, domains of interaction, and blind spots; and (5) attentiveness and responsive relationality. Four examples of pedagogical practices that are illustrative of these clusters are offered: the L'Arche Communities, the conditional teaching of the Mindfulness Research Lab, the purposeless assignment, and the progettazione of the Reggio Emilia approach to early childhood.

The role of complex carbohydrate catabolism in the pathogenesis of invasive streptococci

PubMed Central

Shelburne, Samuel A.; Davenport, Michael T.; Keith, David B.; Musser, James M.

2009-01-01

Historically, the study of bacterial catabolism of complex carbohydrates has contributed to understanding basic bacterial physiology. Recently, however, genome-wide screens of streptococcal pathogenesis have identified genes encoding proteins involved in complex carbohydrate catabolism as participating in pathogen infectivity. Subsequent studies have focused on specific mechanisms by which carbohydrate utilization proteins might contribute to the ability of streptococci to colonize and infect the host. Moreover, transcriptome and biochemical analyses have uncovered novel regulatory pathways by which streptococci link environmental carbohydrate availability to virulence factor production. Herein we review new insights into the role of complex carbohydrates in streptococcal host-pathogen interaction. PMID:18508271

Advances in understanding river-groundwater interactions

NASA Astrophysics Data System (ADS)

Brunner, Philip; Therrien, René; Renard, Philippe; Simmons, Craig T.; Franssen, Harrie-Jan Hendricks

2017-09-01

River-groundwater interactions are at the core of a wide range of major contemporary challenges, including the provision of high-quality drinking water in sufficient quantities, the loss of biodiversity in river ecosystems, or the management of environmental flow regimes. This paper reviews state of the art approaches in characterizing and modeling river and groundwater interactions. Our review covers a wide range of approaches, including remote sensing to characterize the streambed, emerging methods to measure exchange fluxes between rivers and groundwater, and developments in several disciplines relevant to the river-groundwater interface. We discuss approaches for automated calibration, and real-time modeling, which improve the simulation and understanding of river-groundwater interactions. Although the integration of these various approaches and disciplines is advancing, major research gaps remain to be filled to allow more complete and quantitative integration across disciplines. New possibilities for generating realistic distributions of streambed properties, in combination with more data and novel data types, have great potential to improve our understanding and predictive capabilities for river-groundwater systems, especially in combination with the integrated simulation of the river and groundwater flow as well as calibration methods. Understanding the implications of different data types and resolution, the development of highly instrumented field sites, ongoing model development, and the ultimate integration of models and data are important future research areas. These developments are required to expand our current understanding to do justice to the complexity of natural systems.

The Issues Framework: Situating Graduate Teaching Assistant-Student Interactions in Physics Problem Solving

NASA Astrophysics Data System (ADS)

Westlander, Meghan Joanne

Interactive engagement environments are critical to students' conceptual learning gains, and often the instructor is ultimately responsible for the creation of that environment in the classroom. When those instructors are graduate teaching assistants (GTAs), one of the primary ways in which they can promote interactive engagement is through their interactions with students. Much of the prior research on physics GTA-student interactions focuses on GTA training programs (e.g. Ezrailson (2004); Smith, Ward, and Rosenshein (1977)) or on GTAs' specific actions and beliefs (e.g. West, Paul, Webb, and Potter (2013); Goertzen (2010); Spike and Finkelstein (2012a)). Research on students' ideas and behaviors within and surrounding those interactions is limited but important to obtaining a more complete understanding of how GTAs promote an interactive environment. In order to begin understanding this area, I developed the Issues Framework to examine how GTA-student interactions are situated in students' processes during physics problem solving activities. Using grounded theory, the Issues Framework emerged from an analysis of the relationships between GTA-student interactions and the students procedures and expressions of physics content in and surrounding those interactions. This study is focused on introducing the Issues Framework and the insight it can provide into GTA-student interactions and students' processes. The framework is general in nature and has a visually friendly design making it a useful tool for consolidating complex data and quickly pattern-matching important pieces of a complex process. Four different categories of Issues emerged spanning the problem solving process: (1) Getting Started, (2) Solution Approach, (3) Unit Conversions, and (4) Other. The framework allowed for identification of the specific contents of the Issues in each category as well as revealing the common stories of students' processes and how the interactions were situated in those processes in each category. Through the stories, the Issues Framework revealed processes in which students often focused narrowly on procedures with the physics content expressed through their procedures and only sometimes through conceptual discussions. Interactions with the GTA affected changes in students' processes, typically leading students to correct their procedures. The interactions often focused narrowly on procedures as well but introduced conceptual discussions more often than students did surrounding the interactions. Comparing stories across GTAs instead of across categories revealed one GTA who, more often than other GTAs, used conceptual discussion and encouraged students' participation in the interactions. The Issues Framework still needs continued refinement and testing. However, it represents a significant step toward understanding GTA-student interactions from the perspective of students' processes in physics problem solving.

Plant Mediator complex and its critical functions in transcription regulation.

PubMed

Yang, Yan; Li, Ling; Qu, Li-Jia

2016-02-01

The Mediator complex is an important component of the eukaryotic transcriptional machinery. As an essential link between transcription factors and RNA polymerase II, the Mediator complex transduces diverse signals to genes involved in different pathways. The plant Mediator complex was recently purified and comprises conserved and specific subunits. It functions in concert with transcription factors to modulate various responses. In this review, we summarize the recent advances in understanding the plant Mediator complex and its diverse roles in plant growth, development, defense, non-coding RNA production, response to abiotic stresses, flowering, genomic stability and metabolic homeostasis. In addition, the transcription factors interacting with the Mediator complex are also highlighted. © 2015 Institute of Botany, Chinese Academy of Sciences.

A Pedagogical Software for the Analysis of Loudspeaker Systems

ERIC Educational Resources Information Center

Pueo, B.; Roma, M.; Escolano, J.; Lopez, J. J.

2009-01-01

In this paper, a pedagogical software for the design and analysis of loudspeaker systems is presented, with emphasis on training students in the interaction between system parameters. Loudspeakers are complex electromechanical system, whose behavior is neither intuitive nor easy to understand by inexperienced students. Although commercial…

Partnerships for Improving Schools. Contributions to the Study of Education, Number 24.

ERIC Educational Resources Information Center

Jones, Byrd L.; Maloy, Robert W.

Building organizational linkages between schools and other organizations requires many levels of support, trust, volunteered efforts, and complex understandings of social realities. Drawing on documented accounts and the authors' experiences, this volume presents definitions of interactive partnerships, barriers to school improvement and the…

Neuroanatomy and Global Neuroscience.

PubMed

DeFelipe, Javier

2017-07-05

Our brains are like a dense forest-a complex, seemingly impenetrable terrain of interacting cells mediating cognition and behavior. However, we should view the challenge of understanding the brain with optimism, provided that we choose appropriate strategies for the development of global neuroscience. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of future scenarios in understanding deep uncertainty in long-term air quality management

EPA Science Inventory

The environment and its interactions with human systems, whether economic, social or political, are complex. Relevant drivers may disrupt system dynamics in unforeseen ways, making it difficult to predict future conditions. This kind of deep uncertainty presents a challenge to ...

Structural basis for nuclear import complex dissociation by RanGTP.

PubMed

Lee, Soo Jae; Matsuura, Yoshiyuki; Liu, Sai Man; Stewart, Murray

2005-06-02

Nuclear protein import is mediated mainly by the transport factor importin-beta that binds cytoplasmic cargo, most often via the importin-alpha adaptor, and then transports it through nuclear pore complexes. This active transport is driven by disassembly of the import complex by nuclear RanGTP. The switch I and II loops of Ran change conformation with nucleotide state, and regulate its interactions with nuclear trafficking components. Importin-beta consists of 19 HEAT repeats that are based on a pair of antiparallel alpha-helices (referred to as the A- and B-helices). The HEAT repeats stack to yield two C-shaped arches, linked together to form a helicoidal molecule that has considerable conformational flexibility. Here we present the structure of full-length yeast importin-beta (Kap95p or karyopherin-beta) complexed with RanGTP, which provides a basis for understanding the crucial cargo-release step of nuclear import. We identify a key interaction site where the RanGTP switch I loop binds to the carboxy-terminal arch of Kap95p. This interaction produces a change in helicoidal pitch that locks Kap95p in a conformation that cannot bind importin-alpha or cargo. We suggest an allosteric mechanism for nuclear import complex disassembly by RanGTP.

Understanding complex host-microbe interactions in Hydra

PubMed Central

Bosch, Thomas C.G.

2012-01-01

Any multicellular organism may be considered a metaorganism or holobiont—comprised of the macroscopic host and synergistic interdependence with bacteria, archaea, fungi, viruses, and numerous other microbial and eukaryotic species including algal symbionts. Defining the individual microbe-host conversations in these consortia is a challenging but necessary step on the path to understanding the function of the associations as a whole. Dissecting the fundamental principles that underlie all host-microbe interactions requires simple animal models with only a few specific bacterial species. Here I present Hydra as such a model with one of the simplest epithelia in the animal kingdom, with the availability of a fully sequenced genome and numerous genomic tools, and with few associated bacterial species. PMID:22688725

Botulinum neurotoxins: new questions arising from structural biology.

PubMed

Kammerer, Richard A; Benoit, Roger M

2014-11-01

Botulinum neurotoxins (BoNTs) are the most toxic substances known and cause botulism in vertebrates. They have also emerged as effective and powerful reagents for cosmetic and medical applications. One important prerequisite for understanding BoNT function in disease, and the further development of the toxins for cosmetic and medical applications, is a detailed knowledge of BoNT interactions with non-toxic neurotoxin-associated proteins and cell surface receptors. Based on the substantial recent progress in obtaining high-resolution crystal structures of key BoNT complexes, we summarize the major advances in understanding BoNT interactions and discuss the resulting potential implications, in particular those relating to BoNT serotype A. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dynamic regulation of sperm interactions with the zona pellucida prior to and after fertilisation.

PubMed

Gadella, B M

2012-01-01

Recent findings have refined our thinking on sperm interactions with the cumulus-oocyte complex (COC) and our understanding of how, at the molecular level, the sperm cell fertilises the oocyte. Proteomic analyses has identified a capacitation-dependent sperm surface reordering that leads to the formation of functional multiprotein complexes involved in zona-cumulus interactions in several mammalian species. During this process, multiple docking of the acrosomal membrane to the plasma membrane takes place. In contrast with the dogma that the acrosome reaction is initiated when spermatozoa bind to the zona pellucida (ZP), it has been established recently that, in mice, the fertilising spermatozoon initiates its acrosome reaction during its voyage through the cumulus before it reaches the ZP. In fact, even acrosome-reacted mouse spermatozoa collected from the perivitelline space can fertilise another ZP-intact oocyte. The oviduct appears to influence the extracellular matrix properties of the spermatozoa as well as the COC. This may influence sperm binding and penetration of the cumulus and ZP, and, in doing so, increase monospermic while decreasing polyspermic fertilisation rates. Structural analysis of the ZP has shed new light on how spermatozoa bind and penetrate this structure and how the cortical reaction blocks sperm-ZP interactions. The current understanding of sperm interactions with the cumulus and ZP layers surrounding the oocyte is reviewed with a special emphasis on the lack of comparative knowledge on this topic in humans, as well as in most farm mammals.

Mapping the contact surfaces in the Lamin A:AIMP3 complex by hydrogen/deuterium exchange FT-ICR mass spectrometry.

PubMed

Tao, Yeqing; Fang, Pengfei; Kim, Sunghoon; Guo, Min; Young, Nicolas L; Marshall, Alan G

2017-01-01

Aminoacyl-tRNA synthetases-interacting multifunctional protein3 (AIMP3/p18) is involved in the macromolecular tRNA synthetase complex via its interaction with several aminoacyl-tRNA synthetases. Recent reports reveal a novel function of AIMP3 as a tumor suppressor by accelerating cellular senescence and causing defects in nuclear morphology. AIMP3 specifically mediates degradation of mature Lamin A (LmnA), a major component of the nuclear envelope matrix; however, the mechanism of how AIMP3 interacts with LmnA is unclear. Here we report solution-phase hydrogen/deuterium exchange (HDX) for AIMP3, LmnA, and AIMP3 in association with the LmnA C-terminus. Reversed-phase LC coupled with LTQ 14.5 T Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) results in high mass accuracy and resolving power for comparing the D-uptake profiles for AIMP3, LmnA, and their complex. The results show that the AIMP3-LmnA interaction involves one of the two putative binding sites and an adjacent novel interface on AIMP3. LmnA binds AIMP3 via its extreme C-terminus. Together these findings provide a structural insight for understanding the interaction between AIMP3 and LmnA in AIMP3 degradation.

Epistasis interaction of QTL effects as a genetic parameter influencing estimation of the genetic additive effect.

PubMed

Bocianowski, Jan

2013-03-01

Epistasis, an additive-by-additive interaction between quantitative trait loci, has been defined as a deviation from the sum of independent effects of individual genes. Epistasis between QTLs assayed in populations segregating for an entire genome has been found at a frequency close to that expected by chance alone. Recently, epistatic effects have been considered by many researchers as important for complex traits. In order to understand the genetic control of complex traits, it is necessary to clarify additive-by-additive interactions among genes. Herein we compare estimates of a parameter connected with the additive gene action calculated on the basis of two models: a model excluding epistasis and a model with additive-by-additive interaction effects. In this paper two data sets were analysed: 1) 150 barley doubled haploid lines derived from the Steptoe × Morex cross, and 2) 145 DH lines of barley obtained from the Harrington × TR306 cross. The results showed that in cases when the effect of epistasis was different from zero, the coefficient of determination was larger for the model with epistasis than for the one excluding epistasis. These results indicate that epistatic interaction plays an important role in controlling the expression of complex traits.

Periodontal and inflammatory bowel diseases: Is there evidence of complex pathogenic interactions?

PubMed

Lira-Junior, Ronaldo; Figueredo, Carlos Marcelo

2016-09-21

Periodontal disease and inflammatory bowel disease (IBD) are both chronic inflammatory diseases. Their pathogenesis is mediated by a complex interplay between a dysbiotic microbiota and the host immune-inflammatory response, and both are influenced by genetic and environmental factors. This review aimed to provide an overview of the evidence dealing with a possible pathogenic interaction between periodontal disease and IBD. There seems to be an increased prevalence of periodontal disease in patients with IBD when compared to healthy controls, probably due to changes in the oral microbiota and a higher inflammatory response. Moreover, the induction of periodontitis seems to result in gut dysbiosis and altered gut epithelial cell barrier function, which might contribute to the pathogenesis of IBD. Considering the complexity of both periodontal disease and IBD, it is very challenging to understand the possible pathways involved in their coexistence. In conclusion, this review points to a complex pathogenic interaction between periodontal disease and IBD, in which one disease might alter the composition of the microbiota and increase the inflammatory response related to the other. However, we still need more data derived from human studies to confirm results from murine models. Thus, mechanistic studies are definitely warranted to clarify this possible bidirectional association.

Nitrogen Monoxide (NO) Storage and Transport by Dinitrosyl-Dithiol-Iron Complexes: Long-lived NO That Is Trafficked by Interacting Proteins*

PubMed Central

Suryo Rahmanto, Yohan; Kalinowski, Danuta S.; Lane, Darius J. R.; Lok, Hiu Chuen; Richardson, Vera; Richardson, Des R.

2012-01-01

Nitrogen monoxide (NO) markedly affects intracellular iron metabolism, and recent studies have shown that molecules traditionally involved in drug resistance, namely GST and MRP1 (multidrug resistance-associated protein 1), are critical molecular players in this process. This is mediated by interaction of these proteins with dinitrosyl-dithiol-iron complexes (Watts, R. N., Hawkins, C., Ponka, P., and Richardson, D. R. (2006) Proc. Natl. Acad. Sci. U.S.A. 103, 7670–7675; Lok, H. C., Suryo Rahmanto, Y., Hawkins, C. L., Kalinowski, D. S., Morrow, C. S., Townsend, A. J., Ponka, P., and Richardson, D. R. (2012) J. Biol. Chem. 287, 607–618). These complexes are bioavailable, have a markedly longer half-life compared with free NO, and form in cells after an interaction between iron, NO, and glutathione. The generation of dinitrosyl-dithiol-iron complexes acts as a common currency for NO transport and storage by MRP1 and GST P1-1, respectively. Understanding the biological trafficking mechanisms involved in the metabolism of NO is vital for elucidating its many roles in cellular signaling and cytotoxicity and for development of new therapeutic targets. PMID:22262835

Atomic Resolution Modeling of the Ferredoxin:[FeFe] Hydrogenase Complex from Chlamydomonas reinhardtii

PubMed Central

Chang, Christopher H.; King, Paul W.; Ghirardi, Maria L.; Kim, Kwiseon

2007-01-01

The [FeFe] hydrogenases HydA1 and HydA2 in the green alga Chlamydomonas reinhardtii catalyze the final reaction in a remarkable metabolic pathway allowing this photosynthetic organism to produce H2 from water in the chloroplast. A [2Fe-2S] ferredoxin is a critical branch point in electron flow from Photosystem I toward a variety of metabolic fates, including proton reduction by hydrogenases. To better understand the binding determinants involved in ferredoxin:hydrogenase interactions, we have modeled Chlamydomonas PetF1 and HydA2 based on amino-acid sequence homology, and produced two promising electron-transfer model complexes by computational docking. To characterize these models, quantitative free energy calculations at atomic resolution were carried out, and detailed analysis of the interprotein interactions undertaken. The protein complex model we propose for ferredoxin:HydA2 interaction is energetically favored over the alternative candidate by 20 kcal/mol. This proposed model of the electron-transfer complex between PetF1 and HydA2 permits a more detailed view of the molecular events leading up to H2 evolution, and suggests potential mutagenic strategies to modulate electron flow to HydA2. PMID:17660315

Atomic resolution modeling of the ferredoxin:[FeFe] hydrogenase complex from Chlamydomonas reinhardtii.

PubMed

Chang, Christopher H; King, Paul W; Ghirardi, Maria L; Kim, Kwiseon

2007-11-01

The [FeFe] hydrogenases HydA1 and HydA2 in the green alga Chlamydomonas reinhardtii catalyze the final reaction in a remarkable metabolic pathway allowing this photosynthetic organism to produce H(2) from water in the chloroplast. A [2Fe-2S] ferredoxin is a critical branch point in electron flow from Photosystem I toward a variety of metabolic fates, including proton reduction by hydrogenases. To better understand the binding determinants involved in ferredoxin:hydrogenase interactions, we have modeled Chlamydomonas PetF1 and HydA2 based on amino-acid sequence homology, and produced two promising electron-transfer model complexes by computational docking. To characterize these models, quantitative free energy calculations at atomic resolution were carried out, and detailed analysis of the interprotein interactions undertaken. The protein complex model we propose for ferredoxin:HydA2 interaction is energetically favored over the alternative candidate by 20 kcal/mol. This proposed model of the electron-transfer complex between PetF1 and HydA2 permits a more detailed view of the molecular events leading up to H(2) evolution, and suggests potential mutagenic strategies to modulate electron flow to HydA2.

Understanding large multiprotein complexes: applying a multiple allosteric networks model to explain the function of the Mediator transcription complex.

PubMed

Lewis, Brian A

2010-01-15

The regulation of transcription and of many other cellular processes involves large multi-subunit protein complexes. In the context of transcription, it is known that these complexes serve as regulatory platforms that connect activator DNA-binding proteins to a target promoter. However, there is still a lack of understanding regarding the function of these complexes. Why do multi-subunit complexes exist? What is the molecular basis of the function of their constituent subunits, and how are these subunits organized within a complex? What is the reason for physical connections between certain subunits and not others? In this article, I address these issues through a model of network allostery and its application to the eukaryotic RNA polymerase II Mediator transcription complex. The multiple allosteric networks model (MANM) suggests that protein complexes such as Mediator exist not only as physical but also as functional networks of interconnected proteins through which information is transferred from subunit to subunit by the propagation of an allosteric state known as conformational spread. Additionally, there are multiple distinct sub-networks within the Mediator complex that can be defined by their connections to different subunits; these sub-networks have discrete functions that are activated when specific subunits interact with other activator proteins.

A Protein Preparation Method for the High-throughput Identification of Proteins Interacting with a Nuclear Cofactor Using LC-MS/MS Analysis.

PubMed

Tsuchiya, Megumi; Karim, M Rezaul; Matsumoto, Taro; Ogawa, Hidesato; Taniguchi, Hiroaki

2017-01-24

Transcriptional coregulators are vital to the efficient transcriptional regulation of nuclear chromatin structure. Coregulators play a variety of roles in regulating transcription. These include the direct interaction with transcription factors, the covalent modification of histones and other proteins, and the occasional chromatin conformation alteration. Accordingly, establishing relatively quick methods for identifying proteins that interact within this network is crucial to enhancing our understanding of the underlying regulatory mechanisms. LC-MS/MS-mediated protein binding partner identification is a validated technique used to analyze protein-protein interactions. By immunoprecipitating a previously-identified member of a protein complex with an antibody (occasionally with an antibody for a tagged protein), it is possible to identify its unknown protein interactions via mass spectrometry analysis. Here, we present a method of protein preparation for the LC-MS/MS-mediated high-throughput identification of protein interactions involving nuclear cofactors and their binding partners. This method allows for a better understanding of the transcriptional regulatory mechanisms of the targeted nuclear factors.

Human Pyruvate Dehydrogenase Complex E2 and E3BP Core Subunits: New Models and Insights from Molecular Dynamics Simulations.

PubMed

Hezaveh, Samira; Zeng, An-Ping; Jandt, Uwe

2016-05-19

Targeted manipulation and exploitation of beneficial properties of multienzyme complexes, especially for the design of novel and efficiently structured enzymatic reaction cascades, require a solid model understanding of mechanistic principles governing the structure and functionality of the complexes. This type of system-level and quantitative knowledge has been very scarce thus far. We utilize the human pyruvate dehydrogenase complex (hPDC) as a versatile template to conduct corresponding studies. Here we present new homology models of the core subunits of the hPDC, namely E2 and E3BP, as the first time effort to elucidate the assembly of hPDC core based on molecular dynamic simulation. New models of E2 and E3BP were generated and validated at atomistic level for different properties of the proteins. The results of the wild type dimer simulations showed a strong hydrophobic interaction between the C-terminal and the hydrophobic pocket which is the main driving force in the intertrimer binding and the core self-assembly. On the contrary, the C-terminal truncated versions exhibited a drastic loss of hydrophobic interaction leading to a dimeric separation. This study represents a significant step toward a model-based understanding of structure and function of large multienzyme systems like PDC for developing highly efficient biocatalyst or bioreaction cascades.

Integration of cell-free protein coexpression with an enzyme-linked immunosorbent assay enables rapid analysis of protein–protein interactions directly from DNA

PubMed Central

Layton, Curtis J; Hellinga, Homme W

2011-01-01

Assays that integrate detection of binding with cell-free protein expression directly from DNA can dramatically increase the pace at which protein–protein interactions (PPIs) can be analyzed by mutagenesis. In this study, we present a method that combines in vitro protein production with an enzyme-linked immunosorbent assay (ELISA) to measure PPIs. This method uses readily available commodity instrumentation and generic antibody–affinity tag interactions. It is straightforward and rapid to execute, enabling many interactions to be assessed in parallel. In traditional ELISAs, reporter complexes are assembled stepwise with one layer at a time. In the method presented here, all the members of the reporter complex are present and assembled together. The signal strength is dependent on all the intercomponent interaction affinities and concentrations. Although this assay is straightforward to execute, establishing proper conditions and analysis of the results require a thorough understanding of the processes that determine the signal strength. The formation of the fully assembled reporter sandwich can be modeled as a competition between Langmuir adsorption isotherms for the immobilized components and binding equilibria of the solution components. We have shown that modeling this process provides semiquantitative understanding of the effects of affinity and concentration and can guide strategies for the development of experimental protocols. We tested the method experimentally using the interaction between a synthetic ankyrin repeat protein (Off7) and maltose-binding protein. Measurements obtained for a collection of alanine mutations in the interface between these two proteins demonstrate that a range of affinities can be analyzed. PMID:21674663

Vector-virus interactions and transmission dynamics of West Nile virus.

PubMed

Ciota, Alexander T; Kramer, Laura D

2013-12-09

West Nile virus (WNV; Flavivirus; Flaviviridae) is the cause of the most widespread arthropod-borne viral disease in the world and the largest outbreak of neuroinvasive disease ever observed. Mosquito-borne outbreaks are influenced by intrinsic (e.g., vector and viral genetics, vector and host competence, vector life-history traits) and extrinsic (e.g., temperature, rainfall, human land use) factors that affect virus activity and mosquito biology in complex ways. The concept of vectorial capacity integrates these factors to address interactions of the virus with the arthropod host, leading to a clearer understanding of their complex interrelationships, how they affect transmission of vector-borne disease, and how they impact human health. Vertebrate factors including host competence, population dynamics, and immune status also affect transmission dynamics. The complexity of these interactions are further exacerbated by the fact that not only can divergent hosts differentially alter the virus, but the virus also can affect both vertebrate and invertebrate hosts in ways that significantly alter patterns of virus transmission. This chapter concentrates on selected components of the virus-vector-vertebrate interrelationship, focusing specifically on how interactions between vector, virus, and environment shape the patterns and intensity of WNV transmission.

Vector-Virus Interactions and Transmission Dynamics of West Nile Virus

PubMed Central

Ciota, Alexander T.; Kramer, Laura D.

2013-01-01

West Nile virus (WNV; Flavivirus; Flaviviridae) is the cause of the most widespread arthropod-borne viral disease in the world and the largest outbreak of neuroinvasive disease ever observed. Mosquito-borne outbreaks are influenced by intrinsic (e.g., vector and viral genetics, vector and host competence, vector life-history traits) and extrinsic (e.g., temperature, rainfall, human land use) factors that affect virus activity and mosquito biology in complex ways. The concept of vectorial capacity integrates these factors to address interactions of the virus with the arthropod host, leading to a clearer understanding of their complex interrelationships, how they affect transmission of vector-borne disease, and how they impact human health. Vertebrate factors including host competence, population dynamics, and immune status also affect transmission dynamics. The complexity of these interactions are further exacerbated by the fact that not only can divergent hosts differentially alter the virus, but the virus also can affect both vertebrate and invertebrate hosts in ways that significantly alter patterns of virus transmission. This chapter concentrates on selected components of the virus-vector-vertebrate interrelationship, focusing specifically on how interactions between vector, virus, and environment shape the patterns and intensity of WNV transmission. PMID:24351794

MCL-CAw: a refinement of MCL for detecting yeast complexes from weighted PPI networks by incorporating core-attachment structure

PubMed Central

2010-01-01

Background The reconstruction of protein complexes from the physical interactome of organisms serves as a building block towards understanding the higher level organization of the cell. Over the past few years, several independent high-throughput experiments have helped to catalogue enormous amount of physical protein interaction data from organisms such as yeast. However, these individual datasets show lack of correlation with each other and also contain substantial number of false positives (noise). Over these years, several affinity scoring schemes have also been devised to improve the qualities of these datasets. Therefore, the challenge now is to detect meaningful as well as novel complexes from protein interaction (PPI) networks derived by combining datasets from multiple sources and by making use of these affinity scoring schemes. In the attempt towards tackling this challenge, the Markov Clustering algorithm (MCL) has proved to be a popular and reasonably successful method, mainly due to its scalability, robustness, and ability to work on scored (weighted) networks. However, MCL produces many noisy clusters, which either do not match known complexes or have additional proteins that reduce the accuracies of correctly predicted complexes. Results Inspired by recent experimental observations by Gavin and colleagues on the modularity structure in yeast complexes and the distinctive properties of "core" and "attachment" proteins, we develop a core-attachment based refinement method coupled to MCL for reconstruction of yeast complexes from scored (weighted) PPI networks. We combine physical interactions from two recent "pull-down" experiments to generate an unscored PPI network. We then score this network using available affinity scoring schemes to generate multiple scored PPI networks. The evaluation of our method (called MCL-CAw) on these networks shows that: (i) MCL-CAw derives larger number of yeast complexes and with better accuracies than MCL, particularly in the presence of natural noise; (ii) Affinity scoring can effectively reduce the impact of noise on MCL-CAw and thereby improve the quality (precision and recall) of its predicted complexes; (iii) MCL-CAw responds well to most available scoring schemes. We discuss several instances where MCL-CAw was successful in deriving meaningful complexes, and where it missed a few proteins or whole complexes due to affinity scoring of the networks. We compare MCL-CAw with several recent complex detection algorithms on unscored and scored networks, and assess the relative performance of the algorithms on these networks. Further, we study the impact of augmenting physical datasets with computationally inferred interactions for complex detection. Finally, we analyse the essentiality of proteins within predicted complexes to understand a possible correlation between protein essentiality and their ability to form complexes. Conclusions We demonstrate that core-attachment based refinement in MCL-CAw improves the predictions of MCL on yeast PPI networks. We show that affinity scoring improves the performance of MCL-CAw. PMID:20939868

Gene-Environment Interactions in Cardiovascular Disease

PubMed Central

Flowers, Elena; Froelicher, Erika Sivarajan; Aouizerat, Bradley E.

2011-01-01

Background Historically, models to describe disease were exclusively nature-based or nurture-based. Current theoretical models for complex conditions such as cardiovascular disease acknowledge the importance of both biologic and non-biologic contributors to disease. A critical feature is the occurrence of interactions between numerous risk factors for disease. The interaction between genetic (i.e. biologic, nature) and environmental (i.e. non-biologic, nurture) causes of disease is an important mechanism for understanding both the etiology and public health impact of cardiovascular disease. Objectives The purpose of this paper is to describe theoretical underpinnings of gene-environment interactions, models of interaction, methods for studying gene-environment interactions, and the related concept of interactions between epigenetic mechanisms and the environment. Discussion Advances in methods for measurement of genetic predictors of disease have enabled an increasingly comprehensive understanding of the causes of disease. In order to fully describe the effects of genetic predictors of disease, it is necessary to place genetic predictors within the context of known environmental risk factors. The additive or multiplicative effect of the interaction between genetic and environmental risk factors is often greater than the contribution of either risk factor alone. PMID:21684212

Modeling complex and multi-component food systems in molecular dynamics simulations on the example of chocolate conching.

PubMed

Greiner, Maximilian; Sonnleitner, Bettina; Mailänder, Markus; Briesen, Heiko

2014-02-01

Additional benefits of foods are an increasing factor in the consumer's purchase. To produce foods with the properties the consumer demands, understanding the micro- and nanostructure is becoming more important in food research today. We present molecular dynamics (MD) simulations as a tool to study complex and multi-component food systems on the example of chocolate conching. The process of conching is chosen because of the interesting challenges it provides: the components (fats, emulsifiers and carbohydrates) contain diverse functional groups, are naturally fluctuating in their chemical composition, and have a high number of internal degrees of freedom. Further, slow diffusion in the non-aqueous medium is expected. All of these challenges are typical to food systems in general. Simulation results show the suitability of present force fields to correctly model the liquid and crystal density of cocoa butter and sucrose, respectively. Amphiphilic properties of emulsifiers are observed by micelle formation in water. For non-aqueous media, pulling simulations reveal high energy barriers for motion in the viscous cocoa butter. The work for detachment of an emulsifier from the sucrose crystal is calculated and matched with detachment of the head and tail groups separately. Hydrogen bonding is shown to be the dominant interaction between the emulsifier and the crystal surface. Thus, MD simulations are suited to model the interaction between the emulsifier and sugar crystal interface in non-aqueous media, revealing detailed information about the structuring and interactions on a molecular level. With interaction parameters being available for a wide variety of chemical groups, MD simulations are a valuable tool to understand complex and multi-component food systems in general. MD simulations provide a substantial benefit to researchers to verify their hypothesis in dynamic simulations with an atomistic resolution. Rapid rise of computational resources successively increases the complexity and the size of the systems that can be studied.

Business Process Management

NASA Astrophysics Data System (ADS)

Hantry, Francois; Papazoglou, Mike; van den Heuvel, Willem-Jan; Haque, Rafique; Whelan, Eoin; Carroll, Noel; Karastoyanova, Dimka; Leymann, Frank; Nikolaou, Christos; Lammersdorf, Winfried; Hacid, Mohand-Said

Business process management is one of the core drivers of business innovation and is based on strategic technology and capable of creating and successfully executing end-to-end business processes. The trend will be to move from relatively stable, organization-specific applications to more dynamic, high-value ones where business process interactions and trends are examined closely to understand more accurately an application's requirements. Such collaborative, complex end-to-end service interactions give rise to the concept of Service Networks (SNs).

Cationic liposome/DNA complexes: from structure to interactions with cellular membranes.

PubMed

Caracciolo, Giulio; Amenitsch, Heinz

2012-10-01

Gene-based therapeutic approaches are based upon the concept that, if a disease is caused by a mutation in a gene, then adding back the wild-type gene should restore regular function and attenuate the disease phenotype. To deliver the gene of interest, both viral and nonviral vectors are used. Viruses are efficient, but their application is impeded by detrimental side-effects. Among nonviral vectors, cationic liposomes are the most promising candidates for gene delivery. They form stable complexes with polyanionic DNA (lipoplexes). Despite several advantages over viral vectors, the transfection efficiency (TE) of lipoplexes is too low compared with those of engineered viral vectors. This is due to lack of knowledge about the interactions between complexes and cellular components. Rational design of efficient lipoplexes therefore requires deeper comprehension of the interactions between the vector and the DNA as well as the cellular pathways and mechanisms involved. The importance of the lipoplex structure in biological function is revealed in the application of synchrotron small-angle X-ray scattering in combination with functional TE measurements. According to current understanding, the structure of lipoplexes can change upon interaction with cellular membranes and such changes affect the delivery efficiency. Recently, a correlation between the mechanism of gene release from complexes, the structure, and the physical and chemical parameters of the complexes has been established. Studies aimed at correlating structure and activity of lipoplexes are reviewed herein. This is a fundamental step towards rational design of highly efficient lipid gene vectors.

Power of data mining methods to detect genetic associations and interactions.

PubMed

Molinaro, Annette M; Carriero, Nicholas; Bjornson, Robert; Hartge, Patricia; Rothman, Nathaniel; Chatterjee, Nilanjan

2011-01-01

Genetic association studies, thus far, have focused on the analysis of individual main effects of SNP markers. Nonetheless, there is a clear need for modeling epistasis or gene-gene interactions to better understand the biologic basis of existing associations. Tree-based methods have been widely studied as tools for building prediction models based on complex variable interactions. An understanding of the power of such methods for the discovery of genetic associations in the presence of complex interactions is of great importance. Here, we systematically evaluate the power of three leading algorithms: random forests (RF), Monte Carlo logic regression (MCLR), and multifactor dimensionality reduction (MDR). We use the algorithm-specific variable importance measures (VIMs) as statistics and employ permutation-based resampling to generate the null distribution and associated p values. The power of the three is assessed via simulation studies. Additionally, in a data analysis, we evaluate the associations between individual SNPs in pro-inflammatory and immunoregulatory genes and the risk of non-Hodgkin lymphoma. The power of RF is highest in all simulation models, that of MCLR is similar to RF in half, and that of MDR is consistently the lowest. Our study indicates that the power of RF VIMs is most reliable. However, in addition to tuning parameters, the power of RF is notably influenced by the type of variable (continuous vs. categorical) and the chosen VIM. Copyright © 2011 S. Karger AG, Basel.

Nutrigenetics and prostate cancer: 2011 and beyond.

PubMed

Yuan, Yinan; Ferguson, Lynnette R

2011-01-01

Prostate cancer runs in families and shows a clear dietary involvement. Until recently, the key risk gene(s) have proved elusive. We summarise current understandings of nutrient-gene interactions in prostate cancer risk and progression. A MEDLINE-based literature search was conducted. Hypothesis-directed candidate gene approaches provide plausible, albeit statistically weak, nutrient-gene interactions. These are based on early understandings of factors likely to impact on carcinogenesis, including both nutrient and genetic effects on androgen biosynthesis and action, xenobiotic metabolism, DNA damage and DNA repair. Non-hypothesis-directed genome-wide association studies provide much stronger evidence for other genes, not hitherto suspected for involvement. Although only a few of these have been formally tested for dietary associations in well-designed epidemiologic studies, the nature of many of the genes suggests that their activity may be regulated by nutrients. These effects may not only be relevant to prostate cancer susceptibility, but also to disease progression. It will be important to move beyond studying single nucleotide polymorphisms, into more complex chromosomal rearrangements and to epigenetic changes. For future progress, large international cohorts will not only need to provide proof of individual nutrient-gene interactions, but also to relate these to more complex nutrient-gene-gene interactions, as parts of pathways. Bioinformatics and biostatistics will be increasingly important tools in nutrigenetic studies beyond 2011. Copyright © 2011 S. Karger AG, Basel.

Architecture of the human interactome defines protein communities and disease networks

PubMed Central

Huttlin, Edward L.; Bruckner, Raphael J.; Paulo, Joao A.; Cannon, Joe R.; Ting, Lily; Baltier, Kurt; Colby, Greg; Gebreab, Fana; Gygi, Melanie P.; Parzen, Hannah; Szpyt, John; Tam, Stanley; Zarraga, Gabriela; Pontano-Vaites, Laura; Swarup, Sharan; White, Anne E.; Schweppe, Devin K.; Rad, Ramin; Erickson, Brian K.; Obar, Robert A.; Guruharsha, K.G.; Li, Kejie; Artavanis-Tsakonas, Spyros; Gygi, Steven P.; Harper, J. Wade

2017-01-01

The physiology of a cell can be viewed as the product of thousands of proteins acting in concert to shape the cellular response. Coordination is achieved in part through networks of protein-protein interactions that assemble functionally related proteins into complexes, organelles, and signal transduction pathways. Understanding the architecture of the human proteome has the potential to inform cellular, structural, and evolutionary mechanisms and is critical to elucidation of how genome variation contributes to disease1–3. Here, we present BioPlex 2.0 (Biophysical Interactions of ORFEOME-derived complexes), which employs robust affinity purification-mass spectrometry (AP-MS) methodology4 to elucidate protein interaction networks and co-complexes nucleated by more than 25% of protein coding genes from the human genome, and constitutes the largest such network to date. With >56,000 candidate interactions, BioPlex 2.0 contains >29,000 previously unknown co-associations and provides functional insights into hundreds of poorly characterized proteins while enhancing network-based analyses of domain associations, subcellular localization, and co-complex formation. Unsupervised Markov clustering (MCL)5 of interacting proteins identified more than 1300 protein communities representing diverse cellular activities. Genes essential for cell fitness6,7 are enriched within 53 communities representing central cellular functions. Moreover, we identified 442 communities associated with more than 2000 disease annotations, placing numerous candidate disease genes into a cellular framework. BioPlex 2.0 exceeds previous experimentally derived interaction networks in depth and breadth, and will be a valuable resource for exploring the biology of incompletely characterized proteins and for elucidating larger-scale patterns of proteome organization. PMID:28514442

Facilitating trust engenderment in secondary school nurse interactions with students.

PubMed

Summach, Anne H J

2011-04-01

School nurses are involved in a complex framework of interactions with students, other professionals, parents, and administrators. Trust between nurse and student is critical for interaction effectiveness. The goal of this study was to understand through phenomenology the process of engendering trust in school nurse-high school student interactions. The qualitative approach explored school nurse perceptions of experiences interacting with students, yielding insights into nurse- and setting-based factors contributing to the development of trust. Subthemes within these included key behaviors and attributes enhancing trust engenderment in school nurse-student interactions. Study findings were well supported by the existing nursing and psychological research literature. Nurses that purposefully strive to develop trust in young people will maximize adolescent health results.

Studies on the interactions of SAP-1 (an N-terminal truncated form of cystatin S) with its binding partners by CD-spectroscopic and molecular docking methods.

PubMed

Yadav, Vikash Kumar; Mandal, Rahul Shubhra; Puniya, Bhanwar Lal; Singh, Sarman; Yadav, Savita

2015-01-01

SAP-1 is a 113 amino acid long single-chain protein which belongs to the type 2 cystatin gene family. In our previous study, we have purified SAP-1 from human seminal plasma and observed its cross-class inhibitory property. At this time, we report the interaction of SAP-1 with diverse proteases and its binding partners by CD-spectroscopic and molecular docking methods. The circular dichroism (CD) spectroscopic studies demonstrate that the conformation of SAP-1 is changed after its complexation with proteases, and the alterations in protein secondary structure are quantitatively calculated with increase of α-helices and reduction of β-strand content. To get insight into the interactions between SAP-1 and proteases, we make an effort to model the three-dimensional structure of SAP-1 by molecular modeling and verify its stability and viability through molecular dynamics simulations and finally complexed with different proteases using ClusPro 2.0 Server. A high degree of shape complementarity is examined within the complexes, stabilized by a number of hydrogen bonds (HBs) and hydrophobic interactions. Using HB analyses in different protein complexes, we have identified a series of key residues that may be involved in the interactions between SAP-1 and proteases. These findings will assist to understand the mechanism of inhibition of SAP-1 for different proteases and provide intimation for further research.

Molecular orbital studies of the bonding in heavy element organometallics: Progress report

NASA Astrophysics Data System (ADS)

Bursten, B. E.

1988-03-01

Over the past two years we have made considerable progress in the understanding of the bonding in heavy element mononuclear and binuclear complexes. For mononuclear complexes, our strategy has been to study the orbital interactions between the actinide metal center and the surrounding ligands. One particular system which has been studied extensively is X sub 3 AnL (where X = Cp, Cl, NH sub 2 ; An = actinide; and L = neutral or anionic ligand). We are interested not only in the mechanics of the An-X orbital interactions, but also how the relative donor characteristics of X may influence coordination of the fourth ligand L to the actinide. For binuclear systems, we are interested not only in homobimetallic complexes, but also in heterobimetallic complexes containing actinides and transition metals. In order to make the calculations of such large systems tractable, we have transferred the X-alpha-SW codes to the newly acquired Cray XMP24 at the Ohio Supercomputer Center. This has resulted in significant savings of money and time.

Self-organization of network dynamics into local quantized states

DOE PAGES

Nicolaides, Christos; Juanes, Ruben; Cueto-Felgueroso, Luis

2016-02-17

Self-organization and pattern formation in network-organized systems emerges from the collective activation and interaction of many interconnected units. A striking feature of these non-equilibrium structures is that they are often localized and robust: only a small subset of the nodes, or cell assembly, is activated. Understanding the role of cell assemblies as basic functional units in neural networks and socio-technical systems emerges as a fundamental challenge in network theory. A key open question is how these elementary building blocks emerge, and how they operate, linking structure and function in complex networks. Here we show that a network analogue of themore » Swift-Hohenberg continuum model—a minimal-ingredients model of nodal activation and interaction within a complex network—is able to produce a complex suite of localized patterns. Thus, the spontaneous formation of robust operational cell assemblies in complex networks can be explained as the result of self-organization, even in the absence of synaptic reinforcements.« less

Self-organization of network dynamics into local quantized states.

PubMed

Nicolaides, Christos; Juanes, Ruben; Cueto-Felgueroso, Luis

2016-02-17

Self-organization and pattern formation in network-organized systems emerges from the collective activation and interaction of many interconnected units. A striking feature of these non-equilibrium structures is that they are often localized and robust: only a small subset of the nodes, or cell assembly, is activated. Understanding the role of cell assemblies as basic functional units in neural networks and socio-technical systems emerges as a fundamental challenge in network theory. A key open question is how these elementary building blocks emerge, and how they operate, linking structure and function in complex networks. Here we show that a network analogue of the Swift-Hohenberg continuum model-a minimal-ingredients model of nodal activation and interaction within a complex network-is able to produce a complex suite of localized patterns. Hence, the spontaneous formation of robust operational cell assemblies in complex networks can be explained as the result of self-organization, even in the absence of synaptic reinforcements.

Self-organization of network dynamics into local quantized states

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

Nicolaides, Christos; Juanes, Ruben; Cueto-Felgueroso, Luis

Self-organization and pattern formation in network-organized systems emerges from the collective activation and interaction of many interconnected units. A striking feature of these non-equilibrium structures is that they are often localized and robust: only a small subset of the nodes, or cell assembly, is activated. Understanding the role of cell assemblies as basic functional units in neural networks and socio-technical systems emerges as a fundamental challenge in network theory. A key open question is how these elementary building blocks emerge, and how they operate, linking structure and function in complex networks. Here we show that a network analogue of themore » Swift-Hohenberg continuum model—a minimal-ingredients model of nodal activation and interaction within a complex network—is able to produce a complex suite of localized patterns. Thus, the spontaneous formation of robust operational cell assemblies in complex networks can be explained as the result of self-organization, even in the absence of synaptic reinforcements.« less

A dynamic auditory-cognitive system supports speech-in-noise perception in older adults

PubMed Central

Anderson, Samira; White-Schwoch, Travis; Parbery-Clark, Alexandra; Kraus, Nina

2013-01-01

Understanding speech in noise is one of the most complex activities encountered in everyday life, relying on peripheral hearing, central auditory processing, and cognition. These abilities decline with age, and so older adults are often frustrated by a reduced ability to communicate effectively in noisy environments. Many studies have examined these factors independently; in the last decade, however, the idea of the auditory-cognitive system has emerged, recognizing the need to consider the processing of complex sounds in the context of dynamic neural circuits. Here, we use structural equation modeling to evaluate interacting contributions of peripheral hearing, central processing, cognitive ability, and life experiences to understanding speech in noise. We recruited 120 older adults (ages 55 to 79) and evaluated their peripheral hearing status, cognitive skills, and central processing. We also collected demographic measures of life experiences, such as physical activity, intellectual engagement, and musical training. In our model, central processing and cognitive function predicted a significant proportion of variance in the ability to understand speech in noise. To a lesser extent, life experience predicted hearing-in-noise ability through modulation of brainstem function. Peripheral hearing levels did not significantly contribute to the model. Previous musical experience modulated the relative contributions of cognitive ability and lifestyle factors to hearing in noise. Our models demonstrate the complex interactions required to hear in noise and the importance of targeting cognitive function, lifestyle, and central auditory processing in the management of individuals who are having difficulty hearing in noise. PMID:23541911

Molecular dynamics simulation of trp-repressor/operator complex: analysis of hydrogen bond patterns of protein DNA interaction

NASA Astrophysics Data System (ADS)

Suenaga, A.; Yatsu, C.; Komeiji, Y.; Uebayasi, M.; Meguro, T.; Yamato, I.

2000-08-01

Molecular dynamics simulation of Escherichia colitrp-repressor/operator complex was performed to elucidate protein-DNA interactions in solution for 800 ps on special-purpose computer MD-GRAPE. The Ewald summation method was employed to treat the electrostatic interaction without cutoff. DNA kept stable conformation in comparison with the result of the conventional cutoff method. Thus, the trajectories obtained were used to analyze the protein-DNA interaction and to understand the role of dynamics of water molecules forming sequence specific recognition interface. The dynamical cross-correlation map showed a significant positive correlation between the helix-turn-helix DNA-binding motifs and the major grooves of operator DNA. The extensive contact surface was stable during the simulation. Most of the contacts consisted of direct interactions between phosphates of DNA and the protein, but several water-mediated polar contacts were also observed. These water-mediated interactions, which were also seen in the crystal structure (Z. Otwinowski, et al., Nature, 335 (1998) 321) emerged spontaneously from the randomized initial configuration of the solvent. This result suggests the importance of the water-mediated interaction in specific recognition of DNA by the trp-repressor, consistent with X-ray structural information.

A multi-method analysis of the interaction between humic acids and heavy metal ions.

PubMed

Ke, Tao; Li, Lu; Rajavel, Krishnamoorthy; Wang, Zhenyu; Lin, Daohui

2018-03-08

Understanding of the interaction between humic acids (HAs) and heavy metal ions (HMIs) is essential for the assessment of environmental and health risks of HMIs. Multiple analyses, including fluorescence quenching of HAs; solution pH, zeta potential, and hydrodynamic size changes; and coprecipitation of HAs and HMIs, were carried out to investigate the interaction between two HAs and four HMIs (Ag + , Pb 2+ , Cd 2+ , and Cr 3+ ). The HA-HMI interaction mainly included chemical complexation, H + -HMI exchange, electrostatic attraction, and flocculation. The chemical complexation between HAs and HMIs revealed by the Stern-Volmer quenching constant was ordered as Ag < Cd < Pb < Cr. HMIs replaced protons in the acidic functional groups of HAs and thus lowered the pH of the solution. The electrostatic interaction between the negatively charged HAs and HMIs reduced the electronegativity of HAs. Interaction with HMIs, especially the high-valent ions, induced aggregation of HAs, causing precipitation of both HAs and HMIs in the sorptive solution. Cr 3+ flocculated and precipitated HAs, but at high concentrations, it reversed the surface charge of HAs and resuspended them. The HA-HMI interaction increased as the HA acidity and solution pH increased.

Tree species exhibit complex patterns of distribution in bottomland hardwood forests

Treesearch

Luben D Dimov; Jim L Chambers; Brian R. Lockhart

2013-01-01

& Context Understanding tree interactions requires an insight into their spatial distribution. & Aims We looked for presence and extent of tree intraspecific spatial point pattern (random, aggregated, or overdispersed) and interspecific spatial point pattern (independent, aggregated, or segregated). & Methods We established twelve 0.64-ha plots in natural...

USER MANUAL FOR THE EPA THIRD-GENERATION AIR QUALITY MODELING SYSTEM (MODELS-3 VERSION 3.0)

EPA Science Inventory

Models-3 is a flexible software system designed to simplify the development and use of environmental assessment and other decision support tools. It is designed for applications ranging from regulatory and policy analysis to understanding the complex interactions of atmospheri...

SYSTEM INSTALLATION AND OPERATION MANUAL FOR THE EPA THIRD-GENERATION AIR QUALITY MODELING SYSTEM (MODELS-3) VERSION 3.0

EPA Science Inventory

Models-3 is a flexible software system designed to simplify the development and use of environmental assessment and other decision support tools. It is designed for applications ranging from regulatory and policy analysis to understanding the complex interactions of atmospheri...

Recent progress in understanding host immune response to Avian Coccidiosis: Th1 and Th17 responses

USDA-ARS?s Scientific Manuscript database

Host-pathogen interaction leading to protection against coccidiosis is complex, involving many aspects of innate and adaptive immunity to intracellular parasites. The etiologic agent of avian coccidiosis is Eimeria, a genus of eukaryotic obligate intracellular parasites belonging to the phylum Apico...

Geography. Focus on Economics.

ERIC Educational Resources Information Center

Watson, George C., Jr.; Domingo, Vernon; Landman, Margaret; Miller, Glenn; Watson, Carlyjane D.; Hopkins, Martha C.

This book allows students to use two specific geographic perspectives - spatial and ecological - to help them understand spatial patterns and processes and the interaction of living and nonliving elements in complex webs of relationships within nature and between nature and society. The set of 12 lessons include: (1) "Where in the World?…

Co-exposure to ultrafine particulate matter and ozone causes electrocardiogram changes indicative of increased arrhythmia risk in mice

EPA Science Inventory

Numerous studies have shown a relationship between acute air pollution exposure and increased risk for cardiovascular morbidity and mortality. Due to the inherent complexity of air pollution, recent studies have focused on co-exposures to better understand potential interactions....

The RAVE-O Intervention: Connecting Neuroscience to the Classroom

ERIC Educational Resources Information Center

Wolf, Maryanne; Barzillai, Mirit; Gottwald, Stephanie; Miller, Lynne; Spencer, Kathleen; Norton, Elizabeth; Lovett, Maureen; Morris, Robin

2009-01-01

This article explores the ways in which knowledge from the cognitive neurosciences, linguistics, and education interact to deepen our understanding of reading's complexity and to inform reading intervention. We first describe how research on brain abnormalities and naming speed processes has shaped both our conceptualization of reading…

Making Learning Happen: Strategies for an Interactive Classroom.

ERIC Educational Resources Information Center

Golub, Jeffrey N.

This is a book about "conscious learning," the kind of learning that enables students to assess the current level and quality of their language performance and then work to improve that performance deliberately, enthusiastically, and with commitment. The book takes complex, sophisticated understandings and reworks them into ready-to-use…

Social acceptability of forest conditions and management practices: a problem analysis.

Treesearch

Bruce A. Shindler; Mark Brunson; George H. Stankey

2002-01-01

The purpose of this report is to improve understanding of the complex sociopolitical processes related to resource management and to help structure management response to conflict and contentiousness, misunderstanding among participants, and failed citizen-agency interactions. Public acceptance is essential to every resource management decision public agencies must...

A Scaffolding Framework to Support Learning of Emergent Phenomena Using Multi-Agent-Based Simulation Environments

ERIC Educational Resources Information Center

Basu, Satabdi; Sengupta, Pratim; Biswas, Gautam

2015-01-01

Students from middle school to college have difficulties in interpreting and understanding complex systems such as ecological phenomena. Researchers have suggested that students experience difficulties in reconciling the relationships between individuals, populations, and species, as well as the interactions between organisms and their environment…

Chapter 5 - Development of biophysical gradient layers for the LANDFIRE Prototype Project

Treesearch

Lisa Holsinger; Robert E. Keane; Russell Parsons; Eva Karau

2006-01-01

Distributions of plant species are generally continuous, gradually changing across landscapes and blending into each other due to the influence of, and interactions between, a complex array of biophysical gradients (Whittaker 1967; 1975). Key biophysical gradients for understanding vegetation distributions include moisture, temperature, evaporative demand, nutrient...

MODELS-3 INSTALLATION PROCEDURES FOR A PC WITH AN NT OPERATING SYSTEM (MODELS-3 VERSION 4.0)

EPA Science Inventory

Models-3 is a flexible software system designed to simplify the development and use of air quality models and other environmental decision support tools. It is designed for applications ranging from regulatory and policy analysis to understanding the complex interactions of at...

MODELS-3 INSTALLATION PROCEDURES FOR A PERSONAL COMPUTER WITH A NT OPERATING SYSTEM (MODELS-3 VERSION 4.1)

EPA Science Inventory

Models-3 is a flexible system designed to simplify the development and use of air quality models and other environmental decision support tools. It is designed for applications ranging from regulatory and policy analysis to understanding the complex interactions of atmospheric...

Book Review: "The Rhizosphere: Biochemistry and Organic Substances at the Soil-Plant Interface, Second Edition"

USDA-ARS?s Scientific Manuscript database

The complexity of the biological, chemical, and physical interactions occurring in the volume of soil surrounding the root of a growing plant dictates that a multidisciplinary approach must be taken to improve our understanding of this rhizosphere. Hence, "The Rhizosphere: Biochemistry and Organic S...

What Does Culture Have to Do with Teaching Science?

ERIC Educational Resources Information Center

Madden, Lauren; Joshi, Arti

2013-01-01

In nearly every elementary school, plants are an important part of the science curriculum. Understanding basic ideas about plants prepares children to study more complicated scientific concepts including cell biology, genetics and heredity, complex ecosystem interactions, and evolution. It is especially important that teachers of children at the…

Understanding and Advancing Campus Sustainability Using a Systems Framework

ERIC Educational Resources Information Center

Posner, Stephen M.; Stuart, Ralph

2013-01-01

Purpose: University campuses behave as complex systems, and sustainability in higher education is best seen as an emergent quality that arises from interactions both within an institution and between the institution and the environmental and social contexts in which it operates. A framework for strategically prioritizing campus sustainability work…

Aerothermodynamics and Turbulence

DTIC Science & Technology

2013-03-08

Surface Heat Transfer and Detailed Flow Structure Fuel Injection in a Scramjet Combustor Reduced Uncertainty in Complex Flows Addressing... hypersonic flight data to capture shock interaction unsteadiness National Hypersonic Foundational Research Plan Joint Technology Office... Hypersonics Basic Science Roadmap Assessment of SOA and Future Research Directions Ongoing Basic Research for Understanding and Controlling Noise

The integrated phenotype and plasticity of Cuphea PSR23: A semi-domesticated oilseed crop

USDA-ARS?s Scientific Manuscript database

Cuphea PSR23, a semi-domesticated potential oilseed crop, is a selection from an interspecific cross between the wild species Cuphea lanceolata and C. viscosissima. Understanding the extent to which its phenotype is integrated, by studying complex trait interactions and interdependencies, is critica...

Structure-based Understanding of Binding Affinity and Mode of Estrogen Receptor α Agonists and Antagonists.

EPA Science Inventory

The flexible hydrophobic ligand binding pocket (LBP) of estrogen receptor α (ERα) allows the binding of a wide variety of endocrine disruptors. Upon ligand binding, the LBP reshapes around the contours of the ligand and stabilizes the complex by complementary hydrophobic interact...

Person-Oriented Approaches to Profiling Learners in Technology-Rich Learning Environments for Ecological Learner Modeling

ERIC Educational Resources Information Center

Jang, Eunice Eunhee; Lajoie, Susanne P.; Wagner, Maryam; Xu, Zhenhua; Poitras, Eric; Naismith, Laura

2017-01-01

Technology-rich learning environments (TREs) provide opportunities for learners to engage in complex interactions involving a multitude of cognitive, metacognitive, and affective states. Understanding learners' distinct learning progressions in TREs demand inquiry approaches that employ well-conceived theoretical accounts of these multiple facets.…

Structure-Based Understanding of Binding Affinity and Mode of Estrogen Receptor α Agonists and Antagonists

EPA Science Inventory

The flexible hydrophobic ligand binding pocket (LBP) of estrogen receptor α (ERα) allows the binding of a wide variety of endocrine disruptors. Upon ligand binding, the LBP reshapes around the contours of the ligand and stabilizes the complex by complementary hydrophobic interact...

Designing Privacy Notices: Supporting User Understanding and Control

ERIC Educational Resources Information Center

Kelley, Patrick Gage

2013-01-01

Users are increasingly expected to manage complex privacy settings in their normal online interactions. From shopping to social networks, users make decisions about sharing their personal information with corporations and contacts, frequently with little assistance. Current solutions require consumers to read long documents or go out of their way…

Stability of subsystem solutions in agent-based models

NASA Astrophysics Data System (ADS)

Perc, Matjaž

2018-01-01

The fact that relatively simple entities, such as particles or neurons, or even ants or bees or humans, give rise to fascinatingly complex behaviour when interacting in large numbers is the hallmark of complex systems science. Agent-based models are frequently employed for modelling and obtaining a predictive understanding of complex systems. Since the sheer number of equations that describe the behaviour of an entire agent-based model often makes it impossible to solve such models exactly, Monte Carlo simulation methods must be used for the analysis. However, unlike pairwise interactions among particles that typically govern solid-state physics systems, interactions among agents that describe systems in biology, sociology or the humanities often involve group interactions, and they also involve a larger number of possible states even for the most simplified description of reality. This begets the question: when can we be certain that an observed simulation outcome of an agent-based model is actually stable and valid in the large system-size limit? The latter is key for the correct determination of phase transitions between different stable solutions, and for the understanding of the underlying microscopic processes that led to these phase transitions. We show that a satisfactory answer can only be obtained by means of a complete stability analysis of subsystem solutions. A subsystem solution can be formed by any subset of all possible agent states. The winner between two subsystem solutions can be determined by the average moving direction of the invasion front that separates them, yet it is crucial that the competing subsystem solutions are characterised by a proper composition and spatiotemporal structure before the competition starts. We use the spatial public goods game with diverse tolerance as an example, but the approach has relevance for a wide variety of agent-based models.

Electrostatic study of Alanine mutational effects on transcription: application to GATA-3:DNA interaction complex.

PubMed

El-Assaad, Atlal; Dawy, Zaher; Nemer, Georges

2015-01-01

Protein-DNA interaction is of fundamental importance in molecular biology, playing roles in functions as diverse as DNA transcription, DNA structure formation, and DNA repair. Protein-DNA association is also important in medicine; understanding Protein-DNA binding kinetics can assist in identifying disease root causes which can contribute to drug development. In this perspective, this work focuses on the transcription process by the GATA Transcription Factor (TF). GATA TF binds to DNA promoter region represented by `G,A,T,A' nucleotides sequence, and initiates transcription of target genes. When proper regulation fails due to some mutations on the GATA TF protein sequence or on the DNA promoter sequence (weak promoter), deregulation of the target genes might lead to various disorders. In this study, we aim to understand the electrostatic mechanism behind GATA TF and DNA promoter interactions, in order to predict Protein-DNA binding in the presence of mutations, while elaborating on non-covalent binding kinetics. To generate a family of mutants for the GATA:DNA complex, we replaced every charged amino acid, one at a time, with a neutral amino acid like Alanine (Ala). We then applied Poisson-Boltzmann electrostatic calculations feeding into free energy calculations, for each mutation. These calculations delineate the contribution to binding from each Ala-replaced amino acid in the GATA:DNA interaction. After analyzing the obtained data in view of a two-step model, we are able to identify potential key amino acids in binding. Finally, we applied the model to GATA-3:DNA (crystal structure with PDB-ID: 3DFV) binding complex and validated it against experimental results from the literature.

Research Strategy for Modeling the Complexities of Turbine Heat Transfer

NASA Technical Reports Server (NTRS)

Simoneau, Robert J.

1996-01-01

The subject of this paper is a NASA research program, known as the Coolant Flow Management Program, which focuses on the interaction between the internal coolant channel and the external film cooling of a turbine blade and/or vane in an aircraft gas turbine engine. The turbine gas path is really a very complex flow field. The combination of strong pressure gradients, abrupt geometry changes and intersecting surfaces, viscous forces, rotation, and unsteady blade/vane interactions all combine to offer a formidable challenge. To this, in the high pressure turbine, we add the necessity of film cooling. The ultimate goal of the turbine designer is to maintain or increase the high level of turbine performance and at the same time reduce the amount of coolant flow needed to achieve this end. Simply stated, coolant flow is a penalty on the cycle and reduces engine thermal efficiency. Accordingly, understanding the flow field and heat transfer associated with the coolant flow is a priority goal. It is important to understand both the film cooling and the internal coolant flow, particularly their interaction. Thus, the motivation for the Coolant Flow Management Program. The paper will begin with a brief discussion of the management and research strategy, will then proceed to discuss the current attack from the internal coolant side, and will conclude by looking at the film cooling effort - at all times keeping sight of the primary goal the interaction between the two. One of the themes of this paper is that complex heat transfer problems of this nature cannot be attacked by single researchers or even groups of researchers, each working alone. It truly needs the combined efforts of a well-coordinated team to make an impact. It is important to note that this is a government/industry/university team effort.

Understanding peptide competitive inhibition of botulinum neurotoxin A binding to SV2 protein via molecular dynamics simulations.

PubMed

Chang, Shan; He, Hong-Qiu; Shen, Lin; Wan, Hua

2015-10-01

Botulinum neurotoxins (BoNTs) are known as the most toxic natural substances. Synaptic vesicle protein 2 (SV2) has been proposed to be a protein receptor for BoNT/A. Recently, two short peptides (BoNT/A-A2 and SV2C-A3) were designed to inhibit complex formation between the BoNT/A receptor-binding domain (BoNT/A-RBD) and the synaptic vesicle protein 2C luminal domain (SV2C-LD). In this article, the two peptide complex systems are studied by molecular dynamics (MD) simulations. The structural stability analysis indicates that BoNT/A-A2 system is more stable than SV2C-A3 system. The conformational analysis implies that the β-sheet in BoNT/A-A2 system maintains its secondary structure but the two β-strands in SV2C-A3 system have remarkable conformational changes. Based on the calculation of hydrogen bonds, hydrophobic interactions and cation-π interactions, it is found that the internal hydrogen bonds play crucial roles in the structural stability of the peptides. Because of the stable secondary structure, the β-sheet in BoNT/A-A2 system establishes effective interactions at the interface and inhibits BoNT/A-RBD binding to SV2C-LD. In contrast, without other β-strands forming internal hydrogen bonds, the two isolated β-strands in SV2C-A3 system become the random coil. This conformational change breaks important hydrogen bonds and weakens cation-π interaction in the interface, so the complex formation is only partially inhibited by the two β-strands. These results are consistent with experimental studies and may be helpful in understanding the inhibition mechanisms of peptide inhibitors. © 2015 Wiley Periodicals, Inc.

We can work it out: an enactive look at cooperation

PubMed Central

Fantasia, Valentina; De Jaegher, Hanne; Fasulo, Alessandra

2014-01-01

The past years have seen an increasing debate on cooperation and its unique human character. Philosophers and psychologists have proposed that cooperative activities are characterized by shared goals to which participants are committed through the ability to understand each other’s intentions. Despite its popularity, some serious issues arise with this approach to cooperation. First, one may challenge the assumption that high-level mental processes are necessary for engaging in acting cooperatively. If they are, then how do agents that do not possess such ability (preverbal children, or children with autism who are often claimed to be mind-blind) engage in cooperative exchanges, as the evidence suggests? Secondly, to define cooperation as the result of two de-contextualized minds reading each other’s intentions may fail to fully acknowledge the complexity of situated, interactional dynamics and the interplay of variables such as the participants’ relational and personal history and experience. In this paper we challenge such accounts of cooperation, calling for an embodied approach that sees cooperation not only as an individual attitude toward the other, but also as a property of interaction processes. Taking an enactive perspective, we argue that cooperation is an intrinsic part of any interaction, and that there can be cooperative interaction before complex communicative abilities are achieved. The issue then is not whether one is able or not to read the other’s intentions, but what it takes to participate in joint action. From this basic account, it should be possible to build up more complex forms of cooperation as needed. Addressing the study of cooperation in these terms may enhance our understanding of human social development, and foster our knowledge of different ways of engaging with others, as in the case of autism. PMID:25152745

Nursing students learning the pharmacology of diabetes mellitus with complexity-based computerized models: A quasi-experimental study.

PubMed

Dubovi, Ilana; Dagan, Efrat; Sader Mazbar, Ola; Nassar, Laila; Levy, Sharona T

2018-02-01

Pharmacology is a crucial component of medications administration in nursing, yet nursing students generally find it difficult and self-rate their pharmacology skills as low. To evaluate nursing students learning pharmacology with the Pharmacology Inter-Leaved Learning-Cells environment, a novel approach to modeling biochemical interactions using a multiscale, computer-based model with a complexity perspective based on a small set of entities and simple rules. This environment represents molecules, organelles and cells to enhance the understanding of cellular processes, and combines these cells at a higher scale to obtain whole-body interactions. Sophomore nursing students who learned the pharmacology of diabetes mellitus with the Pharmacology Inter-Leaved Learning-Cells environment (experimental group; n=94) or via a lecture-based curriculum (comparison group; n=54). A quasi-experimental pre- and post-test design was conducted. The Pharmacology-Diabetes-Mellitus questionnaire and the course's final exam were used to evaluate students' knowledge of the pharmacology of diabetes mellitus. Conceptual learning was significantly higher for the experimental than for the comparison group for the course final exam scores (unpaired t=-3.8, p<0.001) and for the Pharmacology-Diabetes-Mellitus questionnaire (U=942, p<0.001). The largest effect size for the Pharmacology-Diabetes-Mellitus questionnaire was for the medication action subscale. Analysis of complex-systems component reasoning revealed a significant difference for micro-macro transitions between the levels (F(1, 82)=6.9, p<0.05). Learning with complexity-based computerized models is highly effective and enhances the understanding of moving between micro and macro levels of the biochemical phenomena, this is then related to better understanding of medication actions. Moreover, the Pharmacology Inter-Leaved Learning-Cells approach provides a more general reasoning scheme for biochemical processes, which enhances pharmacology learning beyond the specific topic learned. The present study implies that deeper understanding of pharmacology will support nursing students' clinical decisions and empower their proficiency in medications administration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Structural Basis for Dual-Inhibition Mechanism of a Non-Classical Kazal-Type Serine Protease Inhibitor from Horseshoe Crab in Complex with Subtilisin

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

Shenoy, Rajesh T.; Thangamani, Saravanan; Velazquez-Campoy, Adrian

2011-04-26

Serine proteases play a crucial role in host-pathogen interactions. In the innate immune system of invertebrates, multi-domain protease inhibitors are important for the regulation of host-pathogen interactions and antimicrobial activities. Serine protease inhibitors, 9.3-kDa CrSPI isoforms 1 and 2, have been identified from the hepatopancreas of the horseshoe crab, Carcinoscorpius rotundicauda. The CrSPIs were biochemically active, especially CrSPI-1, which potently inhibited subtilisin (Ki=1.43 nM). CrSPI has been grouped with the non-classical Kazal-type inhibitors due to its unusual cysteine distribution. Here we report the crystal structure of CrSPI-1 in complex with subtilisin at 2.6 Å resolution and the results of biophysicalmore » interaction studies. The CrSPI-1 molecule has two domains arranged in an extended conformation. These two domains act as heads that independently interact with two separate subtilisin molecules, resulting in the inhibition of subtilisin activity at a ratio of 1:2 (inhibitor to protease). Each subtilisin molecule interacts with the reactive site loop from each domain of CrSPI-1 through a standard canonical binding mode and forms a single ternary complex. In addition, we propose the substrate preferences of each domain of CrSPI-1. Domain 2 is specific towards the bacterial protease subtilisin, while domain 1 is likely to interact with the host protease, Furin. Elucidation of the structure of the CrSPI-1: subtilisin (1:2) ternary complex increases our understanding of host-pathogen interactions in the innate immune system at the molecular level and provides new strategies for immunomodulation.« less

Crystallographic analysis of NHERF1–PLCβ3 interaction provides structural basis for CXCR2 signaling in pancreatic cancer

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

Jiang, Yuanyuan; Wang, Shuo; Holcomb, Joshua

2014-04-04

Highlights: • CXCR2–NHERF1–PLCβ3 complex regulates CXCR2 signaling in pancreatic cancer. • The crystal structure of the NHERF1 PDZ1 domain in complex with PLCβ3. • The structure reveals specificity determinants of PDZ1–PLCβ3 interaction. • Endogenous PLCβ3 in pancreatic cancer cells interacts with both PDZ1 and PDZ2. • Structural basis of the PDZ1–PLCβ3 interaction is valuable in selective drug design. - Abstract: The formation of CXCR2–NHERF1–PLCβ3 macromolecular complex in pancreatic cancer cells regulates CXCR2 signaling activity and plays an important role in tumor proliferation and invasion. We previously have shown that disruption of the NHERF1-mediated CXCR2–PLCβ3 interaction abolishes the CXCR2 signaling cascademore » and inhibits pancreatic tumor growth in vitro and in vivo. Here we report the crystal structure of the NHERF1 PDZ1 domain in complex with the C-terminal PLCβ3 sequence. The structure reveals that the PDZ1–PLCβ3 binding specificity is achieved by numerous hydrogen bonds and hydrophobic contacts with the last four PLCβ3 residues contributing to specific interactions. We also show that PLCβ3 can bind both NHERF1 PDZ1 and PDZ2 in pancreatic cancer cells, consistent with the observation that the peptide binding pockets of these PDZ domains are highly structurally conserved. This study provides an understanding of the structural basis for the PDZ-mediated NHERF1–PLCβ3 interaction that could prove valuable in selective drug design against CXCR2-related cancers.« less

Synaptic activity induces input-specific rearrangements in a targeted synaptic protein interaction network.

PubMed

Lautz, Jonathan D; Brown, Emily A; VanSchoiack, Alison A Williams; Smith, Stephen E P

2018-05-27

Cells utilize dynamic, network level rearrangements in highly interconnected protein interaction networks to transmit and integrate information from distinct signaling inputs. Despite the importance of protein interaction network dynamics, the organizational logic underlying information flow through these networks is not well understood. Previously, we developed the quantitative multiplex co-immunoprecipitation platform, which allows for the simultaneous and quantitative measurement of the amount of co-association between large numbers of proteins in shared complexes. Here, we adapt quantitative multiplex co-immunoprecipitation to define the activity dependent dynamics of an 18-member protein interaction network in order to better understand the underlying principles governing glutamatergic signal transduction. We first establish that immunoprecipitation detected by flow cytometry can detect activity dependent changes in two known protein-protein interactions (Homer1-mGluR5 and PSD-95-SynGAP). We next demonstrate that neuronal stimulation elicits a coordinated change in our targeted protein interaction network, characterized by the initial dissociation of Homer1 and SynGAP-containing complexes followed by increased associations among glutamate receptors and PSD-95. Finally, we show that stimulation of distinct glutamate receptor types results in different modular sets of protein interaction network rearrangements, and that cells activate both modules in order to integrate complex inputs. This analysis demonstrates that cells respond to distinct types of glutamatergic input by modulating different combinations of protein co-associations among a targeted network of proteins. Our data support a model of synaptic plasticity in which synaptic stimulation elicits dissociation of preexisting multiprotein complexes, opening binding slots in scaffold proteins and allowing for the recruitment of additional glutamatergic receptors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Molecular trophic markers in marine food webs and their potential use for coral ecology.

PubMed

Leal, Miguel Costa; Ferrier-Pagès, Christine

2016-10-01

Notable advances in ecological genomics have been driven by high-throughput sequencing technology and taxonomically broad sequence repositories that allow us to accurately assess species interactions with great taxonomic resolution. The use of DNA as a marker for ingested food is particularly relevant to address predator-prey interactions and disentangle complex marine food webs. DNA-based methods benefit from reductionist molecular approaches to address ecosystem scale processes, such as community structure and energy flow across trophic levels, among others. Here we review how molecular trophic markers have been used to better understand trophic interactions in the marine environment and their advantages and limitations. We focus on animal groups where research has been focused, such as marine mammals, seabirds, fishes, pelagic invertebrates and benthic invertebrates, and use case studies to illustrate how DNA-based methods unraveled food-web interactions. The potential of molecular trophic markers for disentangling the complex trophic ecology of corals is also discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Skeletal effects of carcinoma of the breast and prostate.

PubMed Central

Percival, R. C.

1986-01-01

Recent research has led to improved understanding of the pathology of skeletal metastases in carcinoma of the breast and prostate. Several humoral mechanisms have been identified which have both primary and secondary consequences on skeletal metabolism and probably depend on the complex interplay of a number of factors derived from tumour tissues. An improved understanding of these interactions may lead to new approaches in the management of these common disorders. Images Fig. 1 PMID:3789624

A study of [Co2(alkyne)(binap)(CO)4] complexes (BINAP=(1,1'-binaphthalene)-2,2'-diylbis(diphenylphosphine)).

PubMed

Gibson, Susan E; Kaufmann, Karina A C; Loch, Jennifer A; Steed, Jonathan W; White, Andrew J P

2005-04-08

Understanding the interaction of chiral ligands, alkynes, and alkenes with cobaltcarbonyl sources is critical to learning more about the mechanism of the catalytic, asymmetric Pauson-Khand reaction. We have successfully characterized complexes of the type [Co2(alkyne)(binap)(CO)4] (BINAP=(1,1'-binaphthalene)-2,2'-diylbis(diphenylphosphine)) and shown that diastereomer interconversion occurs under Pauson-Khand reaction conditions when alkyne=HC[triple bond]CCO2Me. Attempts to isolate [Co2(alkyne)(binap)(CO)x] complexes with coordinated alkenes led to the formation of cobaltacyclopentadiene species.

Assembly of the MHC I peptide-loading complex determined by a conserved ionic lock-switch

PubMed Central

Blees, Andreas; Reichel, Katrin; Trowitzsch, Simon; Fisette, Olivier; Bock, Christoph; Abele, Rupert; Hummer, Gerhard; Schäfer, Lars V.; Tampé, Robert

2015-01-01

Salt bridges in lipid bilayers play a decisive role in the dynamic assembly and downstream signaling of the natural killer and T-cell receptors. Here, we describe the identification of an inter-subunit salt bridge in the membrane within yet another key component of the immune system, the peptide-loading complex (PLC). The PLC regulates cell surface presentation of self-antigens and antigenic peptides via molecules of the major histocompatibility complex class I. We demonstrate that a single salt bridge in the membrane between the transporter associated with antigen processing TAP and the MHC I-specific chaperone tapasin is essential for the assembly of the PLC and for efficient MHC I antigen presentation. Molecular modeling and all-atom molecular dynamics simulations suggest an ionic lock-switch mechanism for the binding of TAP to tapasin, in which an unfavorable uncompensated charge in the ER-membrane is prevented through complex formation. Our findings not only deepen the understanding of the interaction network within the PLC, but also provide evidence for a general interaction principle of dynamic multiprotein membrane complexes in immunity. PMID:26611325

Size does Matter

NASA Astrophysics Data System (ADS)

Vespignani, Alessandro

From schools of fish and flocks of birds, to digital networks and self-organizing biopolymers, our understanding of spontaneously emergent phenomena, self-organization, and critical behavior is in large part due to complex systems science. The complex systems approach is indeed a very powerful conceptual framework to shed light on the link between the microscopic dynamical evolution of the basic elements of the system and the emergence of oscopic phenomena; often providing evidence for mathematical principles that go beyond the particulars of the individual system, thus hinting to general modeling principles. By killing the myth of the ant queen and shifting the focus on the dynamical interaction across the elements of the systems, complex systems science has ushered our way into the conceptual understanding of many phenomena at the core of major scientific and social challenges such as the emergence of consensus, social opinion dynamics, conflicts and cooperation, contagion phenomena. For many years though, these complex systems approaches to real-world problems were often suffering from being oversimplified and not grounded on actual data...

Improving students' understanding by using on-going education research to refine active learning activities in a first-year electronics course

NASA Astrophysics Data System (ADS)

Peter Mazzolini, Alexander; Arthur Daniel, Scott

2016-05-01

Interactive Lecture Demonstrations (ILDs) have been used across introductory university physics as a successful active learning (AL) strategy to improve students' conceptual understanding. We have developed ILDs for more complex topics in our first-year electronics course. In 2006 we began developing ILDs to improve students' conceptual understanding of Operational Amplifiers (OAs) and negative feedback in amplification circuits. The ILDs were used after traditional lecture instruction to help students consolidate their understanding. We developed a diagnostic test, to be administered to students both before and after the ILDs, as a measure of how effective the ILDs were in improving students' understanding.

Moving alcohol prevention research forward-Part I: introducing a complex systems paradigm.

PubMed

Apostolopoulos, Yorghos; Lemke, Michael K; Barry, Adam E; Lich, Kristen Hassmiller

2018-02-01

The drinking environment is a complex system consisting of a number of heterogeneous, evolving and interacting components, which exhibit circular causality and emergent properties. These characteristics reduce the efficacy of commonly used research approaches, which typically do not account for the underlying dynamic complexity of alcohol consumption and the interdependent nature of diverse factors influencing misuse over time. We use alcohol misuse among college students in the United States as an example for framing our argument for a complex systems paradigm. A complex systems paradigm, grounded in socio-ecological and complex systems theories and computational modeling and simulation, is introduced. Theoretical, conceptual, methodological and analytical underpinnings of this paradigm are described in the context of college drinking prevention research. The proposed complex systems paradigm can transcend limitations of traditional approaches, thereby fostering new directions in alcohol prevention research. By conceptualizing student alcohol misuse as a complex adaptive system, computational modeling and simulation methodologies and analytical techniques can be used. Moreover, use of participatory model-building approaches to generate simulation models can further increase stakeholder buy-in, understanding and policymaking. A complex systems paradigm for research into alcohol misuse can provide a holistic understanding of the underlying drinking environment and its long-term trajectory, which can elucidate high-leverage preventive interventions. © 2017 Society for the Study of Addiction.

Cold Flow Propulsion Test Complex Pulse Testing

NASA Technical Reports Server (NTRS)

McDougal, Kris

2016-01-01

When the propellants in a liquid rocket engine burn, the rocket not only launches and moves in space, it causes forces that interact with the vehicle itself. When these interactions occur under specific conditions, the vehicle's structures and components can become unstable. One instability of primary concern is termed pogo (named after the movement of a pogo stick), in which the oscillations (cycling movements) cause large loads, or pressure, against the vehicle, tanks, feedlines, and engine. Marshall Space Flight Center (MSFC) has developed a unique test technology to understand and quantify the complex fluid movements and forces in a liquid rocket engine that contribute strongly to both engine and integrated vehicle performance and stability. This new test technology was established in the MSFC Cold Flow Propulsion Test Complex to allow injection and measurement of scaled propellant flows and measurement of the resulting forces at multiple locations throughout the engine.

Deciphering the complexity of acute inflammation using mathematical models.

PubMed

Vodovotz, Yoram

2006-01-01

Various stresses elicit an acute, complex inflammatory response, leading to healing but sometimes also to organ dysfunction and death. We constructed both equation-based models (EBM) and agent-based models (ABM) of various degrees of granularity--which encompass the dynamics of relevant cells, cytokines, and the resulting global tissue dysfunction--in order to begin to unravel these inflammatory interactions. The EBMs describe and predict various features of septic shock and trauma/hemorrhage (including the response to anthrax, preconditioning phenomena, and irreversible hemorrhage) and were used to simulate anti-inflammatory strategies in clinical trials. The ABMs that describe the interrelationship between inflammation and wound healing yielded insights into intestinal healing in necrotizing enterocolitis, vocal fold healing during phonotrauma, and skin healing in the setting of diabetic foot ulcers. Modeling may help in understanding the complex interactions among the components of inflammation and response to stress, and therefore aid in the development of novel therapies and diagnostics.

Logical Interactions in AN Expanded Space

NASA Astrophysics Data System (ADS)

Tadić, Bosiljka

Understanding the emergent behavior in many complex systems in the physical world and society requires a detailed study of dynamical phenomena occurring and mutually coupled at different scales. The brain processes underlying the social conduct of each, and the emergent social behavior of interacting individuals on a larger scale, represent striking examples of the multiscale complexity. Studies of the human brain, a paradigm of a complex functional system, are enabled by a wealth of brain imaging data that provide clues of how we comprehend space, time, languages, numbers, and differentiate normal from diseased individuals, for example. The social brain, a neural basis for social cognition, represents a dynamically organized part of the brain which is involved in the inference of thoughts, feelings, and intentions going on in the brains of others. Research in this currently unexplored area opens a new perspective on the genesis of the societal organization at different levels and the associated social values...

Identity effects dominate the impacts of multiple species extinctions on the functioning of complex food webs.

PubMed

Harvey, Eric; Séguin, Annie; Nozais, Christian; Archambault, Philippe; Gravel, Dominique

2013-01-01

Understanding the impacts of species extinctions on the functioning of food webs is a challenging task because of the complexity of ecological interactions. We report the impacts of experimental species extinctions on the functioning of two food webs of freshwater and marine systems. We used a linear model to partition the variance among the multiple components of the diversity effect (linear group richness, nonlinear group richness, and identity). The identity of each functional group was the best explaining variable of ecosystem functioning for both systems. We assessed the contribution of each functional group in multifunctional space and found that, although the effect of functional group varied across ecosystem functions, some functional groups shared common effects on functions. This study is the first experimental demonstration that functional identity dominates the effects of extinctions on ecosystem functioning, suggesting that generalizations are possible despite the inherent complexity of interactions.

Emotional valence and context of social influences on drug abuse-related behavior in animal models of social stress and prosocial interaction

PubMed Central

Neisewander, J.L.; Peartree, N.A.; Pentkowski, N.S.

2014-01-01

Rationale Social factors are important determinants of drug dependence and relapse. Objectives We reviewed preclinical literature examining the role of social experiences from early life through the development of drug dependence and relapse, emphasizing two aspects of these experiences: 1) whether the social interaction is appetitive or aversive and 2) whether the social interaction occurs within or outside of the drug-taking context. Methods The models reviewed include neonatal care, isolation, social defeat, chronic subordination, and prosocial interactions. We review results from these models in regard to effects on self-administration and conditioned place preference established with alcohol, psychostimulants, and opiates. Results We suggest that in general, when the interactions occur outside of the drug-taking context, prosocial interactions are protective against drug abuse-related behaviors whereas social stressors facilitate these behaviors. By contrast, positive or negative social interactions occurring within the drug-taking context may interact with other risk factors to enhance or inhibit these behaviors. Conclusions Despite differences in the nature and complexity of human social behavior compared to other species, the evolving animal literature provides useful models for understanding social influences on drug abuse-related behavior that will allow for research on the behavioral and biological mechanisms involved. The models have contributed to understanding social influences on initiation and maintenance of drug use, but more research is needed to understand social influences on drug relapse. PMID:22955569

Biophysical interactions with model lipid membranes: applications in drug discovery and drug delivery

PubMed Central

Peetla, Chiranjeevi; Stine, Andrew; Labhasetwar, Vinod

2009-01-01

The transport of drugs or drug delivery systems across the cell membrane is a complex biological process, often difficult to understand because of its dynamic nature. In this regard, model lipid membranes, which mimic many aspects of cell-membrane lipids, have been very useful in helping investigators to discern the roles of lipids in cellular interactions. One can use drug-lipid interactions to predict pharmacokinetic properties of drugs, such as their transport, biodistribution, accumulation, and hence efficacy. These interactions can also be used to study the mechanisms of transport, based on the structure and hydrophilicity/hydrophobicity of drug molecules. In recent years, model lipid membranes have also been explored to understand their mechanisms of interactions with peptides, polymers, and nanocarriers. These interaction studies can be used to design and develop efficient drug delivery systems. Changes in the lipid composition of cells and tissue in certain disease conditions may alter biophysical interactions, which could be explored to develop target-specific drugs and drug delivery systems. In this review, we discuss different model membranes, drug-lipid interactions and their significance, studies of model membrane interactions with nanocarriers, and how biophysical interaction studies with lipid model membranes could play an important role in drug discovery and drug delivery. PMID:19432455

Network Physiology: How Organ Systems Dynamically Interact

PubMed Central

Bartsch, Ronny P.; Liu, Kang K. L.; Bashan, Amir; Ivanov, Plamen Ch.

2015-01-01

We systematically study how diverse physiologic systems in the human organism dynamically interact and collectively behave to produce distinct physiologic states and functions. This is a fundamental question in the new interdisciplinary field of Network Physiology, and has not been previously explored. Introducing the novel concept of Time Delay Stability (TDS), we develop a computational approach to identify and quantify networks of physiologic interactions from long-term continuous, multi-channel physiological recordings. We also develop a physiologically-motivated visualization framework to map networks of dynamical organ interactions to graphical objects encoded with information about the coupling strength of network links quantified using the TDS measure. Applying a system-wide integrative approach, we identify distinct patterns in the network structure of organ interactions, as well as the frequency bands through which these interactions are mediated. We establish first maps representing physiologic organ network interactions and discover basic rules underlying the complex hierarchical reorganization in physiologic networks with transitions across physiologic states. Our findings demonstrate a direct association between network topology and physiologic function, and provide new insights into understanding how health and distinct physiologic states emerge from networked interactions among nonlinear multi-component complex systems. The presented here investigations are initial steps in building a first atlas of dynamic interactions among organ systems. PMID:26555073

What is the best bonding model of the (σ-H-BR) species bound to a transition metal? Bonding analysis in complexes [(H)2Cl(PMe3)2M(σ-H-BR)] (M = Fe, Ru, Os).

PubMed

Pandey, Krishna K

2012-03-21

Density Functional Theory calculations have been performed for the σ-hydroboryl complexes of iron, ruthenium and osmium [(H)(2)Cl(PMe(3))(2)M(σ-H-BR)] (M = Fe, Ru, Os; R = OMe, NMe(2), Ph) at the BP86/TZ2P/ZORA level of theory in order to understand the interactions between metal and HBR ligands. The calculated geometries of the complexes [(H)(2)Cl(PMe(3))(2)Ru(HBNMe(2))], [(H)(2)Cl(PMe(3))(2)Os(HBR)] (R = OMe, NMe(2)) are in excellent agreement with structurally characterized complexes [(H)(2)Cl(P(i)Pr(3))(2)Os(σ-H-BNMe(2))], [(H)(2)Cl(P(i)Pr(3))(2)Os{σ-H-BOCH(2)CH(2)OB(O(2)CH(2)CH(2))}] and [(H)(2)Cl(P(i)Pr(3))(2)Os(σ-H-BNMe(2))]. The longer calculated M-B bond distance in complex [(H)(2)Cl(PMe(3))(2)M(σ-H-BNMe(2))] are due to greater B-N π bonding and as a result, a weaker M-B π-back-bonding. The B-H2 bond distances reveal that (i) iron complexes contain bis(σ-borane) ligand, (ii) ruthenium complexes contain (σ-H-BR) ligands with a stretched B-H2 bond, and (iii) osmium complexes contain hydride (H2) and (σ-H-BR) ligands. The H-BR ligands in osmium complexes are a better trans-directing ligand than the Cl ligand. Values of interaction energy, electrostatic interaction, orbital interaction, and bond dissociation energy for interactions between ionic fragments are very large and may not be consistent with M-(σ-H-BR) bonding. The EDA as well as NBO and AIM analysis suggest that the best bonding model for the M-σ-H-BR interactions in the complexes [(H)(2)Cl(PMe(3))(2)M(σ-H-BR)] is the interaction between neutral fragments [(H)(2)Cl(PMe(3))(2)M] and [σ-H-BR]. This becomes evident from the calculated values for the orbital interactions. The electron configuration of the fragments which is shown for C in Fig. 1 experiences the smallest change upon the M-σ-H-BR bond formation. Since model C also requires the least amount of electronic excitation and geometry changes of all models given by the ΔE(prep) values, it is clearly the most appropriate choice of interacting fragments. The π-bonding contribution is 14-22% of the total orbital contribution.

Clotrimazole-cyclodextrin based approach for the management and treatment of Candidiasis - A formulation and chemistry-based evaluation.

PubMed

Mohammed, Noorullah Naqvi; Pandey, Pankaj; Khan, Nayaab S; Elokely, Khaled M; Liu, Haining; Doerksen, Robert J; Repka, Michael A

2016-08-01

Clotrimazole (CT) is a poorly soluble antifungal drug that is most commonly employed as a topical treatment in the management of vaginal candidiasis. The present work focuses on a formulation approach to enhance the solubility of CT using cyclodextrin (CD) complexation. A CT-CD complex was prepared by a co-precipitation method. Various characterization techniques such as differential scanning calorimetry, infrared (IR) and X-ray spectroscopy, scanning electron microscopy and nuclear magnetic resonance (NMR) spectroscopy were performed to evaluate the complex formation and to understand the interactions between CT and CD. Computational molecular modeling was performed using the Schrödinger suite and Gaussian 09 program to understand structural conformations of the complex. The phase solubility curve followed an AL-type curve, indicating formation of a 1:1 complex. Molecular docking studies supported the data obtained through NMR and IR studies. Enthalpy changes confirmed that complexation was an exothermic and enthalpically favorable phenomenon. The CT-CD complexes were formulated in a gel and evaluated for release and antifungal activity. The in vitro release studies performed using gels demonstrated a sustained release of CT from the CT-CD complex with the complex exhibiting improved release relative to the un-complexed CT. Complexed CT-CD exhibited better fungistatic activity toward different Candida species than un-complexed CT.

Effect of self-interaction on the evolution of cooperation in complex topologies

NASA Astrophysics Data System (ADS)

Wu, Yu'e.; Zhang, Zhipeng; Chang, Shuhua

2017-09-01

Self-interaction, as a significant mechanism explaining the evolution of cooperation, has attracted great attention both theoretically and experimentally. In this text, we consider a new self-interaction mechanism in the two typical pairwise models including the prisoner's dilemma and the snowdrift games, where the cooperative agents will gain extra bonus for their selfless behavior. We find that under the mechanism the collective cooperation is elevated to a very high level especially after adopting the finite population analogue of replicator dynamics for evolution. The robustness of the new mechanism is tested for different complex topologies for the prisoner's dilemma game. All the presented results demonstrate that the enhancement effects are independent of the structure of the applied spatial networks and the potential evolutionary games, and thus showing a high degree of universality. Our conclusions might shed light on the understanding of the evolution of cooperation in the real world.

Molecular Interaction Map of the Mammalian Cell Cycle Control and DNA Repair Systems

PubMed Central

Kohn, Kurt W.

1999-01-01

Eventually to understand the integrated function of the cell cycle regulatory network, we must organize the known interactions in the form of a diagram, map, and/or database. A diagram convention was designed capable of unambiguous representation of networks containing multiprotein complexes, protein modifications, and enzymes that are substrates of other enzymes. To facilitate linkage to a database, each molecular species is symbolically represented only once in each diagram. Molecular species can be located on the map by means of indexed grid coordinates. Each interaction is referenced to an annotation list where pertinent information and references can be found. Parts of the network are grouped into functional subsystems. The map shows how multiprotein complexes could assemble and function at gene promoter sites and at sites of DNA damage. It also portrays the richness of connections between the p53-Mdm2 subsystem and other parts of the network. PMID:10436023

Forces Driving Chaperone Action

PubMed Central

Koldewey, Philipp; Stull, Frederick; Horowitz, Scott; Martin, Raoul; Bardwell, James C. A.

2016-01-01

SUMMARY It is still unclear what molecular forces drive chaperone-mediated protein folding. Here, we obtain a detailed mechanistic understanding of the forces that dictate the four key steps of chaperone-client interaction: initial binding, complex stabilization, folding, and release. Contrary to the common belief that chaperones recognize unfolding intermediates by their hydrophobic nature, we discover that the model chaperone Spy uses long-range electrostatic interactions to rapidly bind to its unfolded client protein Im7. Short-range hydrophobic interactions follow, which serve to stabilize the complex. Hydrophobic collapse of the client protein then drives its folding. By burying hydrophobic residues in its core, the client’s affinity to Spy decreases, which causes client release. By allowing the client to fold itself, Spy circumvents the need for client-specific folding instructions. This mechanism might help explain how chaperones can facilitate the folding of various unrelated proteins. PMID:27293188

Understanding Structure and Bonding of Multilayered Metal–Organic Nanostructures

PubMed Central

2013-01-01

For organic and hybrid electronic devices, the physicochemical properties of the contained interfaces play a dominant role. To disentangle the various interactions occurring at such heterointerfaces, we here model a complex, yet prototypical, three-component system consisting of a Cu–phthalocyanine (CuPc) film on a 3,4,9,10-perylene-tetracarboxylic-dianhydride (PTCDA) monolayer adsorbed on Ag(111). The two encountered interfaces are similar, as in both cases there would be no bonding without van der Waals interactions. Still, they are also distinctly different, as only at the Ag(111)–PTCDA interface do massive charge-rearrangements occur. Using recently developed theoretical tools, we show that it has become possible to provide atomistic insight into the physical and chemical processes in this comparatively complex nanostructure distinguishing between interactions involving local rearrangements of the charge density and long-range van der Waals attraction. PMID:23447750

Mediator-dependent Nuclear Receptor Functions

PubMed Central

Chen, Wei; Roeder, Robert

2011-01-01

As gene-specific transcription factors, nuclear hormone receptors are broadly involved in many important biological processes. Their function on target genes requires the stepwise assembly of different coactivator complexes that facilitate chromatin remodeling and subsequent preinitiation complex (PIC) formation and function. Mediator has proved to be a crucial, and general, nuclear receptor-interacting coactivator, with demonstrated functions in transcription steps ranging from chromatin remodeling to subsequent PIC formation and function. Here we discuss (i) our current understanding of pathways that nuclear receptors and other interacting cofactors employ to recruit Mediator to target gene enhancers and promoters, including conditional requirements for the strong NR-Mediator interactions mediated by the NR AF2 domain and the MED1 LXXLLL motifs and (ii) mechanisms by which Mediator acts to transmit signals from enhancer-bound nuclear receptors to the general transcription machinery at core promoters to effect PIC formation and function. PMID:21854863

Investigating noncovalent squarylium dye-protein interactions by capillary electrophoresis-frontal analysis.

PubMed

Yan, Weiying; Colyer, Christa L

2006-11-24

Noncovalent interactions between fluorescent probe molecules and protein analyte molecules, which typically occur with great speed and minimal sample handling, form the basis of many high sensitivity analytical techniques. Understanding the nature of these interactions and the composition of the resulting complexes represents an important area of study that can be facilitated by capillary electrophoresis (CE). Specifically, we will present how frontal analysis (FA) and Hummel-Dreyer (HD) methods can be implemented with CE to determine association constants and stoichiometries of noncovalent complexes of the red luminescent squarylium dye Red-1c with bovine serum albumin (BSA) and beta-lactoglobulin A. By adjusting solution conditions, such as pH or ionic strength, it is possible to selectively modify the binding process. As such, conditions for optimal selectivity for labeling reactions can be established by capillary electrophoresis-frontal analysis (CE-FA) investigations.

Demystifying the Complexities of Gravity Wave Dynamics in the Middle Atmosphere: a Roadmap to Improved Weather Forecasts through High-Fidelity Modeling

NASA Astrophysics Data System (ADS)

Mixa, T.; Fritts, D. C.; Bossert, K.; Laughman, B.; Wang, L.; Lund, T.; Kantha, L. H.

2017-12-01

Gravity waves play a profound role in the mixing of the atmosphere, transporting vast amounts of momentum and energy among different altitudes as they propagate vertically. Above 60km in the middle atmosphere, high wave amplitudes enable a series of complex, nonlinear interactions with the background environment that produce highly-localized wind and temperature variations which alter the layering structure of the atmosphere. These small-scale interactions account for a significant portion of energy transport in the middle atmosphere, but they are difficult to characterize, occurring at spatial scales that are both challenging to observe with ground instruments and prohibitively small to include in weather forecasting models. Using high fidelity numerical simulations, these nuanced wave interactions are analyzed to better our understanding of these dynamics and improve the accuracy of long-term weather forecasting.

Carbene footprinting accurately maps binding sites in protein-ligand and protein-protein interactions

NASA Astrophysics Data System (ADS)

Manzi, Lucio; Barrow, Andrew S.; Scott, Daniel; Layfield, Robert; Wright, Timothy G.; Moses, John E.; Oldham, Neil J.

2016-11-01

Specific interactions between proteins and their binding partners are fundamental to life processes. The ability to detect protein complexes, and map their sites of binding, is crucial to understanding basic biology at the molecular level. Methods that employ sensitive analytical techniques such as mass spectrometry have the potential to provide valuable insights with very little material and on short time scales. Here we present a differential protein footprinting technique employing an efficient photo-activated probe for use with mass spectrometry. Using this methodology the location of a carbohydrate substrate was accurately mapped to the binding cleft of lysozyme, and in a more complex example, the interactions between a 100 kDa, multi-domain deubiquitinating enzyme, USP5 and a diubiquitin substrate were located to different functional domains. The much improved properties of this probe make carbene footprinting a viable method for rapid and accurate identification of protein binding sites utilizing benign, near-UV photoactivation.

Integrated Approach for Understanding Impurity Adsorption on Calcite: Mechanisms for Micro-scale Surface Phenomena

NASA Astrophysics Data System (ADS)

Vinson, M. D.; Arvidson, R. S.; Luttge, A.

2004-12-01

A longstanding goal within the field of environmental geochemistry has been the development of a fundamental understanding of the kinetics that governs the interactions of solution-borne impurities with the calcite mineral surface. Recent dissolution experiments using Mg2+, Mn2+, and Sr2+ have shown distinct differences in the interaction of these three impurity ions with the calcite crystal surface. Because the dissolution of carbonate minerals in soils and sediments influences the uptake and migration of groundwater contaminants, a rigorous understanding of the basic processes that occur at the mineral-fluid interface is necessary. We have used vertical scanning interferometry (VSI) coupled with scanning probe microscopy (SPM) to examine calcite crystal dissolution in the presence of Mg2+, Mn2+, and Sr2+, all known dissolution inhibitors and possible groundwater contaminants. We have studied the kinetics of impurity-crystal interactions at a pH 8.8, and in the presence or absence of dissolved inorganic carbon. Our data show that, when individually introduced into undersaturated solutions, Mg2+ and Mn2+ are shown to activate the calcite crystal surface, resulting in enhanced etch pit nucleation rates and step density. Conversely, Sr2+ is shown to cause passivation of the calcite surface. The effect is intensified when solutions are saturated with respect to atmospheric CO2. Results indicate that aqueous CO32- (or HCO3-) may influence how aqueous metal ionic complexes interact with the crystal surface. Furthermore, the influence is differently exhibited, and passivation or activation ultimately depends on the properties of the diffusing metal ion or metal-hydroxide complex. These properties include for example, differences in hydration enthalpy, the effective ionic radius, and electron shell configuration.

Surface energetics and protein-protein interactions: analysis and mechanistic implications

PubMed Central

Peri, Claudio; Morra, Giulia; Colombo, Giorgio

2016-01-01

Understanding protein-protein interactions (PPI) at the molecular level is a fundamental task in the design of new drugs, the prediction of protein function and the clarification of the mechanisms of (dis)regulation of biochemical pathways. In this study, we use a novel computational approach to investigate the energetics of aminoacid networks located on the surface of proteins, isolated and in complex with their respective partners. Interestingly, the analysis of individual proteins identifies patches of surface residues that, when mapped on the structure of their respective complexes, reveal regions of residue-pair couplings that extend across the binding interfaces, forming continuous motifs. An enhanced effect is visible across the proteins of the dataset forming larger quaternary assemblies. The method indicates the presence of energetic signatures in the isolated proteins that are retained in the bound form, which we hypothesize to determine binding orientation upon complex formation. We propose our method, BLUEPRINT, as a complement to different approaches ranging from the ab-initio characterization of PPIs, to protein-protein docking algorithms, for the physico-chemical and functional investigation of protein-protein interactions. PMID:27050828

Chaperone-client complexes: A dynamic liaison

NASA Astrophysics Data System (ADS)

Hiller, Sebastian; Burmann, Björn M.

2018-04-01

Living cells contain molecular chaperones that are organized in intricate networks to surveil protein homeostasis by avoiding polypeptide misfolding, aggregation, and the generation of toxic species. In addition, cellular chaperones also fulfill a multitude of alternative functionalities: transport of clients towards a target location, help them fold, unfold misfolded species, resolve aggregates, or deliver clients towards proteolysis machineries. Until recently, the only available source of atomic resolution information for virtually all chaperones were crystal structures of their client-free, apo-forms. These structures were unable to explain details of the functional mechanisms underlying chaperone-client interactions. The difficulties to crystallize chaperones in complexes with clients arise from their highly dynamic nature, making solution NMR spectroscopy the method of choice for their study. With the advent of advanced solution NMR techniques, in the past few years a substantial number of structural and functional studies on chaperone-client complexes have been resolved, allowing unique insight into the chaperone-client interaction. This review summarizes the recent insights provided by advanced high-resolution NMR-spectroscopy to understand chaperone-client interaction mechanisms at the atomic scale.

Beyond information access: Support for complex cognitive activities in public health informatics tools.

PubMed

Sedig, Kamran; Parsons, Paul; Dittmer, Mark; Ola, Oluwakemi

2012-01-01

Public health professionals work with a variety of information sources to carry out their everyday activities. In recent years, interactive computational tools have become deeply embedded in such activities. Unlike the early days of computational tool use, the potential of tools nowadays is not limited to simply providing access to information; rather, they can act as powerful mediators of human-information discourse, enabling rich interaction with public health information. If public health informatics tools are designed and used properly, they can facilitate, enhance, and support the performance of complex cognitive activities that are essential to public health informatics, such as problem solving, forecasting, sense-making, and planning. However, the effective design and evaluation of public health informatics tools requires an understanding of the cognitive and perceptual issues pertaining to how humans work and think with information to perform such activities. This paper draws on research that has examined some of the relevant issues, including interaction design, complex cognition, and visual representations, to offer some human-centered design and evaluation considerations for public health informatics tools.

The effect of paracetamol on 5 fluorouracil and bovine serum albumin interaction: A biophysical study

NASA Astrophysics Data System (ADS)

Dahiya, Vandana; Pal, Samanwita

2018-05-01

Serum Albumin is a major carrier protein and its binding with drugs is important to examine the change in pharmacokinetic properties due to interaction amongst drugs. In the present study we have attempted to understand the relevant drug-drug interaction (DDI) between two common drugs viz, paracetamol, an anti-inflammatory and fluorouracil, an anti-cancer drug. In-vitro spectroscopic methods viz., fluorescence quenching and UV-vis absorption have been employed for the drug-bovine serum albumin (BSA) complexes studies. The binding parameters and quenching constants have been determined for BSA-Paracetamol and BSA-5Fluorouracil complex according to literature models. It is also predicted from the quenching studies that BSA-5Fluorouracil is a stronger complex than BSA-Paracetamol. On the other hand paracetamol can alter binding affinity of 5Fluorouracil towards BSA. Hence it becomes clear that although the drugs could be administered simultaneously but they influence each other's binding with protein in a concentration dependent fashion. Further these results also indicate that availability of free 5Fluorouracil in blood may increase in presence of paracetamol.

Filamin 2 (Fln2)

PubMed Central

Thompson, Terri G.; Chan, Yiu-Mo; Hack, Andrew A.; Brosius, Melissa; Rajala, Michael; Lidov, Hart G.W.; McNally, Elizabeth M.; Watkins, Simon; Kunkel, Louis M.

2000-01-01

Mutations in genes encoding for the sarcoglycans, a subset of proteins within the dystrophin–glycoprotein complex, produce a limb-girdle muscular dystrophy phenotype; however, the precise role of this group of proteins in the skeletal muscle is not known. To understand the role of the sarcoglycan complex, we looked for sarcoglycan interacting proteins with the hope of finding novel members of the dystrophin–glycoprotein complex. Using the yeast two-hybrid method, we have identified a skeletal muscle-specific form of filamin, which we term filamin 2 (FLN2), as a γ- and δ-sarcoglycan interacting protein. In addition, we demonstrate that FLN2 protein localization in limb-girdle muscular dystrophy and Duchenne muscular dystrophy patients and mice is altered when compared with unaffected individuals. Previous studies of filamin family members have determined that these proteins are involved in actin reorganization and signal transduction cascades associated with cell migration, adhesion, differentiation, force transduction, and survival. Specifically, filamin proteins have been found essential in maintaining membrane integrity during force application. The finding that FLN2 interacts with the sarcoglycans introduces new implications for the pathogenesis of muscular dystrophy. PMID:10629222

New levels of language processing complexity and organization revealed by granger causation.

PubMed

Gow, David W; Caplan, David N

2012-01-01

Granger causation analysis of high spatiotemporal resolution reconstructions of brain activation offers a new window on the dynamic interactions between brain areas that support language processing. Premised on the observation that causes both precede and uniquely predict their effects, this approach provides an intuitive, model-free means of identifying directed causal interactions in the brain. It requires the analysis of all non-redundant potentially interacting signals, and has shown that even "early" processes such as speech perception involve interactions of many areas in a strikingly large network that extends well beyond traditional left hemisphere perisylvian cortex that play out over hundreds of milliseconds. In this paper we describe this technique and review several general findings that reframe the way we think about language processing and brain function in general. These include the extent and complexity of language processing networks, the central role of interactive processing dynamics, the role of processing hubs where the input from many distinct brain regions are integrated, and the degree to which task requirements and stimulus properties influence processing dynamics and inform our understanding of "language-specific" localized processes.

The plasma dynamics of hypersonic spacecraft: Applications of laboratory simulations and active in situ experiments

NASA Technical Reports Server (NTRS)

Stone, N. H.; Samir, Uri

1986-01-01

Attempts to gain an understanding of spacecraft plasma dynamics via experimental investigation of the interaction between artificially synthesized, collisionless, flowing plasmas and laboratory test bodies date back to the early 1960's. In the past 25 years, a number of researchers have succeeded in simulating certain limited aspects of the complex spacecraft-space plasma interaction reasonably well. Theoretical treatments have also provided limited models of the phenomena. Several active experiments were recently conducted from the space shuttle that specifically attempted to observe the Orbiter-ionospheric interaction. These experiments have contributed greatly to an appreciation for the complexity of spacecraft-space plasma interaction but, so far, have answered few questions. Therefore, even though the plasma dynamics of hypersonic spacecraft is fundamental to space technology, it remains largely an open issue. A brief overview is provided of the primary results from previous ground-based experimental investigations and the preliminary results of investigations conducted on the STS-3 and Spacelab 2 missions. In addition, several, as yet unexplained, aspects of the spacecraft-space plasma interaction are suggested for future research.

Chemotaxing and haptotaxing random walkers having directional persistence

NASA Astrophysics Data System (ADS)

Kwon, Tae Goo; Kyoungjin Lee Team; Taeseok Daniel Yang Team

2015-03-01

Biological cell crawling is a rather complex process involving various bio-chemical and bio-mechanical processes, many of which are still not well understood. The difficulties in understanding the crawling are originating not just from cell-intrinsic factors but from their complex social interactions, cell-to-substrate interactions and nonlinear responses toward extrinsic factors. Here, in this report we investigate chemotactic behavior of mathematical model cells that naturally have directional persistence. A cell density is measured as a function of time and space, then the resulting steady state is compared with that of the well-known Keller-Segal model, which describes a population of chemotactic random walker. Then, we add a cell-to-cell interaction, mimicking a ``haptotaxis'' mediated interaction, to the model and access its role as for altering the steady-state cell density profile. This mathematical model system, which we have developed and considered in this work, can be quite relevant to the chemotactic responses of interacting immune cells, like microglia, moving toward and around a site of wound, as for an example. We conclude by discussing some relevant recent experimental findings.

Impact of lipid rafts on the T -cell-receptor and peptide-major-histocompatibility-complex interactions under different measurement conditions

NASA Astrophysics Data System (ADS)

Li, Long; Xu, Guang-Kui; Song, Fan

2017-01-01

The interactions between T-cell receptor (TCR) and peptide-major-histocompatibility complex (pMHC), which enable T-cell development and initiate adaptive immune responses, have been intensively studied. However, a central issue of how lipid rafts affect the TCR-pMHC interactions remains unclear. Here, by using a statistical-mechanical membrane model, we show that the binding affinity of TCR and pMHC anchored on two apposing cell membranes is significantly enhanced because of the lipid raft-induced signaling protein aggregation. This finding may provide an alternative insight into the mechanism of T-cell activation triggered by very low densities of pMHC. In the case of cell-substrate adhesion, our results indicate that the loss of lateral mobility of the proteins on the solid substrate leads to the inhibitory effect of lipid rafts on TCR-pMHC interactions. Our findings help to understand why different experimental methods for measuring the impact of lipid rafts on the receptor-ligand interactions have led to contradictory conclusions.

Modulation by clamping: Kv4 and KChIP interactions.

PubMed

Wang, Kewei

2008-10-01

The rapidly inactivating (A-type) potassium channels regulate membrane excitability that defines the fundamental mechanism of neuronal functions such as pain signaling. Cytosolic Kv channel-interacting proteins KChIPs that belong to neuronal calcium sensor (NCS) family of calcium binding EF-hand proteins co-assemble with Kv4 (Shal) alpha subunits to form a native complex that encodes major components of neuronal somatodendritic A-type K+ current, I(SA), in neurons and transient outward current, I(TO), in cardiac myocytes. The specific binding of auxiliary KChIPs to the Kv4 N-terminus results in modulation of gating properties, surface expression and subunit assembly of Kv4 channels. Here, I attempt to emphasize the interaction between KChIPs and Kv4 based on recent progress made in understanding the structure complex in which a single KChIP1 molecule laterally clamps two neighboring Kv4.3 N-termini in a 4:4 manner. Greater insights into molecular mechanism between KChIPs and Kv4 interaction may provide therapeutic potentials of designing compounds aimed at disrupting the protein-protein interaction for treatment of membrane excitability-related disorders.

The meaning ascribed to wheeled mobility devices by individuals who use wheelchairs and scooters: a metasynthesis.

PubMed

Ripat, Jacquie; Verdonck, Michele; Carter, Roger Jaffrey

2018-04-01

To synthesize qualitative study findings on the meaning ascribed to wheelchairs and wheeled mobility devices (WMD) by WMD users. Bibliographic databases were systematically searched up to January 2015 to identify relevant papers. Reviewers selected studies, assessed methodological quality and thematically synthesized findings using a metasynthesis process described by Thomas and Harden (2008). Twenty articles were included. Four descriptive themes emerged: physical environment interaction; sociocultural experiences; participation in activities and occupations; and WMD-self relationship. WMD use was found to be a complex experience that can fluctuate through interaction with aspects of the environment and opportunities for participation. The analytic theme, dynamic duality of WMD experience, addressed the simultaneous enabling and disabling aspects of WMD use. Metasyntheses enable researchers to gain a deeper understanding of issues by examining findings across studies. Findings of this study provide a framework for understanding the complexity of WMD use. The framework has practical applications for clinicians and users of WMD in understanding the experience of WMD to be neither singular nor static. Implications for Rehabilitation The meaning of wheeled mobility device (WMD) use is dynamically influenced by the environment and opportunities afforded for occupational and social participation. A duality of experiences can emerge for WMD users, where wheeled mobility use can be at the same time positive and negative, based on the interaction with the environment. Clinicians need to determine the meaning that each individual user ascribes to the WMD, and to consider how that meaning may change over time. By understanding the meaning ascribed to WMD use by individuals, clinicians can be better prepared to work with the WMD users to address negative reinforcers of the experience in physical and sociocultural environments as well as highlighting the positive experiences.

Exploring oral literacy in communication with hospice caregivers.

PubMed

Wittenberg-Lyles, Elaine; Goldsmith, Joy; Oliver, Debra Parker; Demiris, George; Kruse, Robin L; Van Stee, Stephanie

2013-11-01

Low oral literacy has been identified as a barrier to pain management for informal caregivers who receive verbal instructions on pain medication and pain protocols. To examine recorded communication between hospice staff and informal caregivers and explore caregiver experiences. Using transcripts of interactions (n = 47), oral literacy features were analyzed by examining the generalized language complexity using the Flesch-Kincaid grading scale and the dialogue interactivity defined by talking turns and interaction time. Means for longitudinal follow-up measures on caregiver anxiety, quality of life, perception of pain management, knowledge and comfort providing pain medication, and satisfaction were examined to explore their relationship to oral literacy. Communication between team members and caregivers averaged a fourth-grade level on the Flesch-Kincaid scale, indicating that communication was easy to understand. Reading ease was associated (r = 0.67, P < 0.05) with caregiver understanding of and comfort with pain management. Perceived barriers to caregiver pain management were lower when sessions had increased use of passive sentences (r = 0.61, P < 0.01), suggesting that passive voice was not an accurate indicator of language complexity. Caregiver understanding and comfort with administering pain medications (r = -0.82, P < 0.01) and caregiver quality of life (r = -0.49, P < 0.05) were negatively correlated with dialogue pace. As the grade level of talk with caregivers and hospice teams increased, associated caregiver anxiety increased. Caregivers with higher anxiety also experienced greater difficulty in understanding pain medication and its management. Specific adjustments that hospice teams can make to improve caregiver experiences are identified. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Systems biology-based approaches toward understanding drought tolerance in food crops.

PubMed

Jogaiah, Sudisha; Govind, Sharathchandra Ramsandra; Tran, Lam-Son Phan

2013-03-01

Economically important crops, such as maize, wheat, rice, barley, and other food crops are affected by even small changes in water potential at important growth stages. Developing a comprehensive understanding of host response to drought requires a global view of the complex mechanisms involved. Research on drought tolerance has generally been conducted using discipline-specific approaches. However, plant stress response is complex and interlinked to a point where discipline-specific approaches do not give a complete global analysis of all the interlinked mechanisms. Systems biology perspective is needed to understand genome-scale networks required for building long-lasting drought resistance. Network maps have been constructed by integrating multiple functional genomics data with both model plants, such as Arabidopsis thaliana, Lotus japonicus, and Medicago truncatula, and various food crops, such as rice and soybean. Useful functional genomics data have been obtained from genome-wide comparative transcriptome and proteome analyses of drought responses from different crops. This integrative approach used by many groups has led to identification of commonly regulated signaling pathways and genes following exposure to drought. Combination of functional genomics and systems biology is very useful for comparative analysis of other food crops and has the ability to develop stable food systems worldwide. In addition, studying desiccation tolerance in resurrection plants will unravel how combination of molecular genetic and metabolic processes interacts to produce a resurrection phenotype. Systems biology-based approaches have helped in understanding how these individual factors and mechanisms (biochemical, molecular, and metabolic) "interact" spatially and temporally. Signaling network maps of such interactions are needed that can be used to design better engineering strategies for improving drought tolerance of important crop species.

Inception of self-interacting dark matter with dark charge conjugation symmetry

DOE PAGES

Ma, Ernest

2017-07-04

A new understanding of the stability of self-interacting dark matter is pointed out, based on the simplest spontaneously broken Abelian gauge model with one complex scalar and one Dirac fermion. The key is the imposition of dark charge conjugation symmetry. It allows the possible existence of two stable particles: the Dirac fermion and the vector gauge boson which acts as a light mediator for the former's self-interaction. Since this light mediator does not decay, it avoids the strong cosmological constraints recently obtained for all such models where the light mediator decays into standard-model particles.

A conservation and biophysics guided stochastic approach to refining docked multimeric proteins.

PubMed

Akbal-Delibas, Bahar; Haspel, Nurit

2013-01-01

We introduce a protein docking refinement method that accepts complexes consisting of any number of monomeric units. The method uses a scoring function based on a tight coupling between evolutionary conservation, geometry and physico-chemical interactions. Understanding the role of protein complexes in the basic biology of organisms heavily relies on the detection of protein complexes and their structures. Different computational docking methods are developed for this purpose, however, these methods are often not accurate and their results need to be further refined to improve the geometry and the energy of the resulting complexes. Also, despite the fact that complexes in nature often have more than two monomers, most docking methods focus on dimers since the computational complexity increases exponentially due to the addition of monomeric units. Our results show that the refinement scheme can efficiently handle complexes with more than two monomers by biasing the results towards complexes with native interactions, filtering out false positive results. Our refined complexes have better IRMSDs with respect to the known complexes and lower energies than those initial docked structures. Evolutionary conservation information allows us to bias our results towards possible functional interfaces, and the probabilistic selection scheme helps us to escape local energy minima. We aim to incorporate our refinement method in a larger framework which also enables docking of multimeric complexes given only monomeric structures.

SCOWLP classification: Structural comparison and analysis of protein binding regions

PubMed Central

Teyra, Joan; Paszkowski-Rogacz, Maciej; Anders, Gerd; Pisabarro, M Teresa

2008-01-01

Background Detailed information about protein interactions is critical for our understanding of the principles governing protein recognition mechanisms. The structures of many proteins have been experimentally determined in complex with different ligands bound either in the same or different binding regions. Thus, the structural interactome requires the development of tools to classify protein binding regions. A proper classification may provide a general view of the regions that a protein uses to bind others and also facilitate a detailed comparative analysis of the interacting information for specific protein binding regions at atomic level. Such classification might be of potential use for deciphering protein interaction networks, understanding protein function, rational engineering and design. Description Protein binding regions (PBRs) might be ideally described as well-defined separated regions that share no interacting residues one another. However, PBRs are often irregular, discontinuous and can share a wide range of interacting residues among them. The criteria to define an individual binding region can be often arbitrary and may differ from other binding regions within a protein family. Therefore, the rational behind protein interface classification should aim to fulfil the requirements of the analysis to be performed. We extract detailed interaction information of protein domains, peptides and interfacial solvent from the SCOWLP database and we classify the PBRs of each domain family. For this purpose, we define a similarity index based on the overlapping of interacting residues mapped in pair-wise structural alignments. We perform our classification with agglomerative hierarchical clustering using the complete-linkage method. Our classification is calculated at different similarity cut-offs to allow flexibility in the analysis of PBRs, feature especially interesting for those protein families with conflictive binding regions. The hierarchical classification of PBRs is implemented into the SCOWLP database and extends the SCOP classification with three additional family sub-levels: Binding Region, Interface and Contacting Domains. SCOWLP contains 9,334 binding regions distributed within 2,561 families. In 65% of the cases we observe families containing more than one binding region. Besides, 22% of the regions are forming complex with more than one different protein family. Conclusion The current SCOWLP classification and its web application represent a framework for the study of protein interfaces and comparative analysis of protein family binding regions. This comparison can be performed at atomic level and allows the user to study interactome conservation and variability. The new SCOWLP classification may be of great utility for reconstruction of protein complexes, understanding protein networks and ligand design. SCOWLP will be updated with every SCOP release. The web application is available at . PMID:18182098

Structure and Function of Iron-Loaded Synthetic Melanin

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

Li, Yiwen; Xie, Yijun; Wang, Zhao

We describe a synthetic method for increasing and controlling the iron loading of synthetic melanin nanoparticles and use the resulting materials to perform a systematic quantitative investigation on their structure- property relationship. A comprehensive analysis by magnetometry, electron paramagnetic resonance, and nuclear magnetic relaxation dispersion reveals the complexities of their magnetic behavior and how these intraparticle magnetic interactions manifest in useful material properties such as their performance as MRI contrast agents. This analysis allows predictions of the optimal iron loading through a quantitative modeling of antiferromagnetic coupling that arises from proximal iron ions. This study provides a detailed understanding ofmore » this complex class of synthetic biomaterials and gives insight into interactions and structures prevalent in naturally occurring melanins.« less

Versatile communication strategies among tandem WW domain repeats

PubMed Central

Dodson, Emma Joy; Fishbain-Yoskovitz, Vered; Rotem-Bamberger, Shahar

2015-01-01

Interactions mediated by short linear motifs in proteins play major roles in regulation of cellular homeostasis since their transient nature allows for easy modulation. We are still far from a full understanding and appreciation of the complex regulation patterns that can be, and are, achieved by this type of interaction. The fact that many linear-motif-binding domains occur in tandem repeats in proteins indicates that their mutual communication is used extensively to obtain complex integration of information toward regulatory decisions. This review is an attempt to overview, and classify, different ways by which two and more tandem repeats cooperate in binding to their targets, in the well-characterized family of WW domains and their corresponding polyproline ligands. PMID:25710931

Multiple scales modelling approaches to social interaction in crowd dynamics and crisis management. Comment on "Human behaviours in evacuation crowd dynamics: From modelling to "big data" toward crisis management" by Nicola Bellomo et al.

NASA Astrophysics Data System (ADS)

Trucu, Dumitru

2016-09-01

In this comprehensive review concerning the modelling of human behaviours in crowd dynamics [3], the authors explore a wide range of mathematical approaches spanning over multiple scales that are suitable to describe emerging crowd behaviours in extreme situations. Focused on deciphering the key aspects leading to emerging crowd patterns evolutions in challenging times such as those requiring an evacuation on a complex venue, the authors address this complex dynamics at both microscale (individual level), mesoscale (probability distributions of interacting individuals), and macroscale (population level), ultimately aiming to gain valuable understanding and knowledge that would inform decision making in managing crisis situations.

Cross-Correlations and Structures of Aero-Engine Gas Path System Based on DCCA Coefficient and Rooted Tree

NASA Astrophysics Data System (ADS)

Dong, Keqiang; Fan, Jie; Gao, You

2015-12-01

Identifying the mutual interaction is a crucial problem that facilitates the understanding of emerging structures in complex system. We here focus on aero-engine dynamic as an example of complex system. By applying the detrended cross-correlation analysis (DCCA) coefficient method to aero-engine gas path system, we find that the low-spool rotor speed (N1) and high-spool rotor speed (N2) fluctuation series exhibit cross-correlation characteristic. Further, we employ detrended cross-correlation coefficient matrix and rooted tree to investigate the mutual interactions of other gas path variables. The results can infer that the exhaust gas temperature (EGT), N1, N2, fuel flow (WF) and engine pressure ratio (EPR) are main gas path parameters.

Entering AN ERA of Synthesis of Modeling

NASA Astrophysics Data System (ADS)

Guerin, Stephen

First, I believe we're entering an era of synthesis of modeling. Over the past 20 years, we've seen the proliferation of many isolated complex systems models. I think we now need tools for researchers, policy makers and the public to share models. Sharing could happen by stacking different layers of spatial agent-based models in geographic information systems and projecting interactive visualization out onto shared surfaces. Further, we need to make model authoring tools much more accessible to the point where motivated policy makers can author on their own. With the increased ability to author and share models, I believe this will allow us to scale our research to understand and manage the many interacting systems that make up our complex world...

Predator functional response and prey survival: Direct and indirect interactions affecting a marked prey population

USGS Publications Warehouse

Miller, David A.; Grand, J.B.; Fondell, T.F.; Anthony, M.

2006-01-01

1. Predation plays an integral role in many community interactions, with the number of predators and the rate at which they consume prey (i.e. their functional response) determining interaction strengths. Owing to the difficulty of directly observing predation events, attempts to determine the functional response of predators in natural systems are limited. Determining the forms that predator functional responses take in complex systems is important in advancing understanding of community interactions. 2. Prey survival has a direct relationship to the functional response of their predators. We employed this relationship to estimate the functional response for bald eagle Haliaeetus leucocepalus predation of Canada goose Branta canadensis nests. We compared models that incorporated eagle abundance, nest abundance and alternative prey presence to determine the form of the functional response that best predicted intra-annual variation in survival of goose nests. 3. Eagle abundance, nest abundance and the availability of alternative prey were all related to predation rates of goose nests by eagles. There was a sigmoidal relationship between predation rate and prey abundance and prey switching occurred when alternative prey was present. In addition, predation by individual eagles increased as eagle abundance increased. 4. A complex set of interactions among the three species examined in this study determined survival rates of goose nests. Results show that eagle predation had both prey- and predator-dependent components with no support for ratio dependence. In addition, indirect interactions resulting from the availability of alternative prey had an important role in mediating the rate at which eagles depredated nests. As a result, much of the within-season variation in nest survival was due to changing availability of alternative prey consumed by eagles. 5. Empirical relationships drawn from ecological theory can be directly integrated into the estimation process to determine the mechanisms responsible for variation in observed survival rates. The relationship between predator functional response and prey survival offers a flexible and robust method to advance our understanding of predator-prey interactions in many complex natural systems where prey populations are marked and regularly visited. ?? 2006 British Ecological Society.

Influence of chemical disorder on energy dissipation and defect evolution in concentrated solid solution alloys

PubMed Central

Zhang, Yanwen; Stocks, G. Malcolm; Jin, Ke; Lu, Chenyang; Bei, Hongbin; Sales, Brian C.; Wang, Lumin; Béland, Laurent K.; Stoller, Roger E.; Samolyuk, German D.; Caro, Magdalena; Caro, Alfredo; Weber, William J.

2015-01-01

A grand challenge in materials research is to understand complex electronic correlation and non-equilibrium atomic interactions, and how such intrinsic properties and dynamic processes affect energy transfer and defect evolution in irradiated materials. Here we report that chemical disorder, with an increasing number of principal elements and/or altered concentrations of specific elements, in single-phase concentrated solid solution alloys can lead to substantial reduction in electron mean free path and orders of magnitude decrease in electrical and thermal conductivity. The subsequently slow energy dissipation affects defect dynamics at the early stages, and consequentially may result in less deleterious defects. Suppressed damage accumulation with increasing chemical disorder from pure nickel to binary and to more complex quaternary solid solutions is observed. Understanding and controlling energy dissipation and defect dynamics by altering alloy complexity may pave the way for new design principles of radiation-tolerant structural alloys for energy applications. PMID:26507943

Investigation of the Dynamics of Coherent Structure, BBF, and Intermittent Turbulence in Earth's Magnetotail: A Study of Complexity in Nonlinear Space Plasmas

NASA Technical Reports Server (NTRS)

Chang, Tom

2005-01-01

We have achieved all the goals stated in our grant proposal. Specifically, these include: 1. The understanding of the complexity induced nonlinear spatiotemporal coherent structures and the coexisting propagating modes. 2. The understanding of the intermittent turbulence and energization process of the observed Bursty Bulk Flows (BBF's) in the Earth s magnetotail. 3. The development of "anisotropic three-dimensional complexity" in the plasma sheet due to localized merging and interactions of the magnetic coherent structures. 4. The study of fluctuation-induced nonlinear instabilities and their role in the reconfiguration of magnetic topologies in the magnetotail based on the concepts of the dynamic renormalization group. 5. The acceleration of ions due to the intermittent turbulence of propagating and nonpropagating fluctuations. In the following, we include lists of our published papers, invited talks, and professional activities. A detailed description of our accomplished research results is given..

Unraveling dynamics of human physical activity patterns in chronic pain conditions

NASA Astrophysics Data System (ADS)

Paraschiv-Ionescu, Anisoara; Buchser, Eric; Aminian, Kamiar

2013-06-01

Chronic pain is a complex disabling experience that negatively affects the cognitive, affective and physical functions as well as behavior. Although the interaction between chronic pain and physical functioning is a well-accepted paradigm in clinical research, the understanding of how pain affects individuals' daily life behavior remains a challenging task. Here we develop a methodological framework allowing to objectively document disruptive pain related interferences on real-life physical activity. The results reveal that meaningful information is contained in the temporal dynamics of activity patterns and an analytical model based on the theory of bivariate point processes can be used to describe physical activity behavior. The model parameters capture the dynamic interdependence between periods and events and determine a `signature' of activity pattern. The study is likely to contribute to the clinical understanding of complex pain/disease-related behaviors and establish a unified mathematical framework to quantify the complex dynamics of various human activities.