The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells.

PubMed

Huang, Chenhui; Jia, Pingping; Chastain, Megan; Shiva, Olga; Chai, Weihang

2017-06-15

Maintaining functional telomeres is important for long-term proliferation of cells. About 15% of cancer cells are telomerase-negative and activate the alternative-lengthening of telomeres (ALT) pathway to maintain their telomeres. Recent studies have shown that the human CTC1/STN1/TEN1 complex (CST) plays a multi-faceted role in telomere maintenance in telomerase-expressing cancer cells. However, the role of CST in telomere maintenance in ALT cells is unclear. Here, we report that human CST forms a functional complex localizing in the ALT-associated PML bodies (APBs) in ALT cells throughout the cell cycle. Suppression of CST induces telomere instabilities including telomere fragility and elevates telomeric DNA recombination, leading to telomere dysfunction. In addition, CST deficiency significantly diminishes the abundance of extrachromosomal circular telomere DNA known as C-circles and t-circles. Suppression of CST also results in multinucleation in ALT cells and impairs cell proliferation. Our findings imply that the CST complex plays an important role in regulating telomere maintenance in ALT cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Global trade and assisted reproductive technologies: regulatory challenges in international surrogacy.

PubMed

Nelson, Erin

2013-01-01

International surrogacy is an increasingly common phenomenon and an important global health challenge. Legal rules are a key consideration for the participants in international surrogacy arrangements. In some cases the law can help to resolve the complex issues that arise in this context, but it is important to consider the role played by law in contributing to the complex conflicts that such arrangements can generate. © 2013 American Society of Law, Medicine & Ethics, Inc.

The role of syntax in complex networks: Local and global importance of verbs in a syntactic dependency network

NASA Astrophysics Data System (ADS)

Čech, Radek; Mačutek, Ján; Žabokrtský, Zdeněk

2011-10-01

Syntax of natural language has been the focus of linguistics for decades. The complex network theory, being one of new research tools, opens new perspectives on syntax properties of the language. Despite numerous partial achievements, some fundamental problems remain unsolved. Specifically, although statistical properties typical for complex networks can be observed in all syntactic networks, the impact of syntax itself on these properties is still unclear. The aim of the present study is to shed more light on the role of syntax in the syntactic network structure. In particular, we concentrate on the impact of the syntactic function of a verb in the sentence on the complex network structure. Verbs play the decisive role in the sentence structure (“local” importance). From this fact we hypothesize the importance of verbs in the complex network (“global” importance). The importance of verb in the complex network is assessed by the number of links which are directed from the node representing verb to other nodes in the network. Six languages (Catalan, Czech, Dutch, Hungarian, Italian, Portuguese) were used for testing the hypothesis.

Prions, prionoid complexes and amyloids: the bad, the good and something in between.

PubMed

Hafner Bratkovič, Iva

2017-04-19

Prions are infectious agents causing transmissible spongiform encephalopathies in humans and animals. These protein-based particles template conformational changes in a host-encoded prion protein to an insoluble self-like conformation. Prions are also present in yeast, where they support protein-based epigenetic inheritance. There is emerging evidence that prion-like (prionoid) particles can support a variety of pathological and beneficial functions. The recent data on the prionoid spread of other pathological amyloids are discussed in light of differences between prions and prion-like aggregates. On the other hand, prion-like action has also been found to support important functions such as memory, and amyloids were shown to have a variety of physiological roles from storage to scaffolding in simple organisms and in humans. Higher-order protein complexes play important roles in signalling. Many death-fold domains can polymerise upon nucleation to enhance sensitivity and induce a robust response. Although these polymers are structurally different from amyloids, some of them are characterised by prionoid activities, such as intercellular spread. The initial activation of these complexes is vital for organismal health, whereas prolonged activation leading to unresolved inflammation underlies autoinflammatory and other diseases. Prionoid complexes play important roles far beyond prion diseases and neurodegeneration.

Emerging role for corticotropin releasing factor signaling in the bed nucleus of the stria terminalis at the intersection of stress and reward.

PubMed

Silberman, Yuval; Winder, Danny G

2013-01-01

Stress and anxiety play an important role in the development and maintenance of drug and alcohol addiction. The bed nucleus of the stria terminalis (BNST), a brain region involved in the production of long-term stress-related behaviors, plays an important role in animal models of relapse, such as reinstatement to previously extinguished drug-seeking behaviors. While a number of neurotransmitter systems have been suggested to play a role in these behaviors, recent evidence points to the neuropeptide corticotropin releasing factor (CRF) as being critically important in BNST-mediated reinstatement behaviors. Although numerous studies indicate that the BNST is a complex brain region with multiple afferent and efferent systems and a variety of cell types, there has only been limited work to determine how CRF modulates this complex neuronal system at the circuit level. Recent work from our lab and others have begun to unravel these BNST neurocircuits and explore their roles in CRF-related reinstatement behaviors. This review will examine the role of CRF signaling in drug addiction and reinstatement with an emphasis on critical neurocircuitry within the BNST that may offer new insights into treatments for addiction.

Design of Arithmetic Circuits for Complex Binary Number System

NASA Astrophysics Data System (ADS)

Jamil, Tariq

2011-08-01

Complex numbers play important role in various engineering applications. To represent these numbers efficiently for storage and manipulation, a (-1+j)-base complex binary number system (CBNS) has been proposed in the literature. In this paper, designs of nibble-size arithmetic circuits (adder, subtractor, multiplier, divider) have been presented. These circuits can be incorporated within von Neumann and associative dataflow processors to achieve higher performance in both sequential and parallel computing paradigms.

Catalytic Activity of Thiolate-Bridged Diruthenium Complexes Bearing Pendent Ether Moieties in the Oxidation of Molecular Dihydrogen.

PubMed

Yuki, Masahiro; Sakata, Ken; Kikuchi, Shoma; Kawai, Hiroyuki; Takahashi, Tsuyoshi; Ando, Masaki; Nakajima, Kazunari; Nishibayashi, Yoshiaki

2017-01-23

Thiolate-bridged diruthenium complexes bearing pendent ethers have been found to work as effective catalysts toward the oxidation of molecular dihydrogen into protons and electrons in water. The pendent ether moiety in the complex plays an important role to facilitate the proton transfer between the metal center and the external proton acceptor. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Aspects of Complexity in Sleep Analysis

NASA Astrophysics Data System (ADS)

Leitão, José M. N.; Da Rosa, Agostinho C.

The paper presents a selection of sleep analysis problems where some aspects and concepts of complexity come about. Emphasis is given to the electroencephalogram (EEG) as the most important sleep related variable. The conception of the EEG as a message to be deciphered stresses the importance of the communication and information theories in this field. An optimal detector of K complexes and vertex sharp waves based on a stochastic model of sleep EEG is considered. Besides detecting, the algorithm is also able to follow the evolution of the basic ongoing activity. It is shown that both the ostructure and microstructure of sleep can be described in terms of symbols and interpreted as sentences of a language. Syntactic models and Markov chain representations play in this context an important role.

Negative regulation of BMP signaling by the ski oncoprotein.

PubMed

Luo, Kunxin

2003-01-01

The bone morphogenetic proteins (BMPs) play important roles in the regulation of multiple aspects of vertebrate development. BMPs signal through the cell surface receptors and downstream Smad molecules. Upon stimulation with BMP, Smad1, Smad5, and Smad8 are phosphorylated by the activated BMP receptors, form a complex with Smad4, and translocate into the nucleus, where they regulate the expression of BMP target genes. The activity of this signal pathway can be modulated both by extracellular factors that regulate the binding of BMPs to the receptor and by intracellular proteins that interact with the Smad proteins. We have shown that Ski is an important negative regulator of the Smad proteins. Ski can bind to the BMP-Smad protein complexes in response to BMP and repress their ability to activate BMP target genes through disruption of a functional Smad complex and through recruitment of transcriptional co-repressors. The antagonism of BMP signaling by Ski results in neural specification in Xenopus embryos and inhibition of osteoblast differentiation in mouse bone-marrow stromal progenitor cells. This ability to modulate BMP signaling by Ski may play an important role in the regulation of craniofacial, neuronal, and skeletal muscle development.

Complex systems dynamics in aging: new evidence, continuing questions.

PubMed

Cohen, Alan A

2016-02-01

There have long been suggestions that aging is tightly linked to the complex dynamics of the physiological systems that maintain homeostasis, and in particular to dysregulation of regulatory networks of molecules. This review synthesizes recent work that is starting to provide evidence for the importance of such complex systems dynamics in aging. There is now clear evidence that physiological dysregulation--the gradual breakdown in the capacity of complex regulatory networks to maintain homeostasis--is an emergent property of these regulatory networks, and that it plays an important role in aging. It can be measured simply using small numbers of biomarkers. Additionally, there are indications of the importance during aging of emergent physiological processes, functional processes that cannot be easily understood through clear metabolic pathways, but can nonetheless be precisely quantified and studied. The overall role of such complex systems dynamics in aging remains an important open question, and to understand it future studies will need to distinguish and integrate related aspects of aging research, including multi-factorial theories of aging, systems biology, bioinformatics, network approaches, robustness, and loss of complexity.

Preprotein import into chloroplasts via the Toc and Tic complexes is regulated by redox signals in Pisum sativum.

PubMed

Stengel, Anna; Benz, J Philipp; Buchanan, Bob B; Soll, Jürgen; Bölter, Bettina

2009-11-01

The import of nuclear-encoded preproteins is necessary to maintain chloroplast function. The recognition and transfer of most precursor proteins across the chloroplast envelopes are facilitated by two membrane-inserted protein complexes, the translocons of the chloroplast outer and inner envelope (Toc and Tic complexes, respectively). Several signals have been invoked to regulate the import of preproteins. In our study, we were interested in redox-based import regulation mediated by two signals: regulation based on thiols and on the metabolic NADP+/NADPH ratio. We sought to identify the proteins participating in the regulation of these transport pathways and to characterize the preprotein subgroups whose import is redox-dependent. Our results provide evidence that the formation and reduction of disulfide bridges in the Toc receptors and Toc translocation channel have a strong influence on import yield of all tested preproteins that depend on the Toc complex for translocation. Furthermore, the metabolic NADP+/NADPH ratio influences not only the composition of the Tic complex, but also the import efficiency of most, but not all, preproteins tested. Thus, several Tic subcomplexes appear to participate in the translocation of different preprotein subgroups, and the redox-active components of these complexes likely play a role in regulating transport.

Does constructive neutral evolution play an important role in the origin of cellular complexity? Making sense of the origins and uses of biological complexity.

PubMed

Speijer, Dave

2011-05-01

Recently, constructive neutral evolution has been touted as an important concept for the understanding of the emergence of cellular complexity. It has been invoked to help explain the development and retention of, amongst others, RNA splicing, RNA editing and ribosomal and mitochondrial respiratory chain complexity. The theory originated as a welcome explanation of isolated small scale cellular idiosyncrasies and as a reaction to 'overselectionism'. Here I contend, that in its extended form, it has major conceptual problems, can not explain observed patterns of complex processes, is too easily dismissive of alternative selectionist models, underestimates the creative force of complexity as such, and--if seen as a major evolutionary mechanism for all organisms--could stifle further thought regarding the evolution of highly complex biological processes. Copyright © 2011 WILEY Periodicals, Inc.

The Knight of Faith: Ethics in Special Needs Education

ERIC Educational Resources Information Center

Steinnes, Jenny

2011-01-01

This article attempts to contribute to the understanding of the particularly important and inescapable role that ethics must play in the context of special needs education. Perspectives from Kierkegaard and Derrida are presented and used in order to explore the complexity of the context and to show the importance and responsibility of the agency…

Alliance of Glycobiologists for Detection of Cancer | Division of Cancer Prevention

Cancer.gov

A consortium of eight Tumor Glycomics Laboratories is working to reveal cancer-related dynamics of complex carbohydrates to develop new, validated clinical biomarkers for early detection. Studying important biologic mechanisms, Alliance investigators focus their efforts on diverse classes of glycan markers that are likely to play important roles in cancer development. | 8

Recent advances in research on volatile aroma compounds in tomatoes and their impacting factors

USDA-ARS?s Scientific Manuscript database

Aroma is an important sensory attribute of tomatoes. Tomato aroma is formed by a complex mixture of more than 400 volatile compounds, and it plays an important role in the classification and consumer acceptability of tomato products. This article provides a brief overview of the volatile aroma compo...

Genetics Home Reference: familial porencephaly

MedlinePlus

... one component of a protein called type IV collagen. Type IV collagen molecules attach to each other to form complex ... and support cells in many tissues. Type IV collagen networks play an important role in the basement ...

Hemispheric asymmetry in stress processing in rat prefrontal cortex and the role of mesocortical dopamine.

PubMed

Sullivan, R M

2004-06-01

The prefrontal cortex (PFC) is known to play an important role not only in the regulation of emotion, but in the integration of affective states with appropriate modulation of autonomic and neuroendocrine stress regulatory systems. The present review highlights findings in the rat which helps to elucidate the complex nature of prefrontal involvement in emotion and stress regulation. The medial PFC is particularly important in this regard and while dorsomedial regions appear to play a suppressive role in such regulation, the ventromedial (particularly infralimbic) region appears to activate behavioral, neuroendocrine and sympathetic autonomic systems in response to stressful situations. This may be especially true of spontaneous stress-related behavior or physiological responses to relatively acute stressors. The role of the medial PFC is somewhat more complex in conditions involving learned adjustments to stressful situations, such as the extinction of conditioned fear responses, but it is clear that the medial PFC is important in incorporating stressful experience for future adaptive behavior. It is also suggested that mesocortical dopamine plays an important adaptive role in this region by preventing excessive behavioral and physiological stress reactivity. The rat brain shows substantial hemispheric specialization in many respects, and while the right PFC is normally dominant in the activation of stress-related systems, the left may play a role in countering this activation through processes of interhemispheric inhibition. This proposed basic template for the lateralization of stress regulatory systems is suggested to be associated with efficient stress and emotional self-regulation, and also to be shaped by both early postnatal experience and gender differences.

Nonmechanical Roles of Dystrophin and Associated Proteins in Exercise, Neuromuscular Junctions, and Brains

PubMed Central

Nichols, Bailey; Takeda, Shin’ichi; Yokota, Toshifumi

2015-01-01

Dystrophin-glycoprotein complex (DGC) is an important structural unit in skeletal muscle that connects the cytoskeleton (f-actin) of a muscle fiber to the extracellular matrix (ECM). Several muscular dystrophies, such as Duchenne muscular dystrophy, Becker muscular dystrophy, congenital muscular dystrophies (dystroglycanopathies), and limb-girdle muscular dystrophies (sarcoglycanopathies), are caused by mutations in the different DGC components. Although many early studies indicated DGC plays a crucial mechanical role in maintaining the structural integrity of skeletal muscle, recent studies identified novel roles of DGC. Beyond a mechanical role, these DGC members play important signaling roles and act as a scaffold for various signaling pathways. For example, neuronal nitric oxide synthase (nNOS), which is localized at the muscle membrane by DGC members (dystrophin and syntrophins), plays an important role in the regulation of the blood flow during exercise. DGC also plays important roles at the neuromuscular junction (NMJ) and in the brain. In this review, we will focus on recently identified roles of DGC particularly in exercise and the brain. PMID:26230713

The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells

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

Huang, Chenhui; Jia, Pingping; Chastain, Megan

Maintaining functional telomeres is important for long-term proliferation of cells. About 15% of cancer cells are telomerase-negative and activate the alternative-lengthening of telomeres (ALT) pathway to maintain their telomeres. Recent studies have shown that the human CTC1/STN1/TEN1 complex (CST) plays a multi-faceted role in telomere maintenance in telomerase-expressing cancer cells. However, the role of CST in telomere maintenance in ALT cells is unclear. Here, we report that human CST forms a functional complex localizing in the ALT-associated PML bodies (APBs) in ALT cells throughout the cell cycle. Suppression of CST induces telomere instabilities including telomere fragility and elevates telomeric DNAmore » recombination, leading to telomere dysfunction. In addition, CST deficiency significantly diminishes the abundance of extrachromosomal circular telomere DNA known as C-circles and t-circles. Suppression of CST also results in multinucleation in ALT cells and impairs cell proliferation. Our findings imply that the CST complex plays an important role in regulating telomere maintenance in ALT cells. - Highlights: • CST localizes at telomeres and ALT-associated PML bodies in ALT cells throughout the cell cycle. • CST is important for promoting telomeric DNA replication in ALT cells. • CST deficiency decreases ECTR formation and increases T-SCE. • CST deficiency impairs ALT cell proliferation and results in multinucleation.« less

Autophagy plays an important role in protecting Pacific oysters from OsHV-1 and Vibrio aestuarianus infections

PubMed Central

Moreau, Pierrick; Moreau, Kevin; Segarra, Amélie; Tourbiez, Delphine; Travers, Marie-Agnès; Rubinsztein, David C; Renault, Tristan

2015-01-01

Recent mass mortality outbreaks around the world in Pacific oysters, Crassostrea gigas, have seriously affected the aquaculture economy. Although the causes for these mortality outbreaks appear complex, infectious agents are involved. Two pathogens are associated with mass mortality outbreaks, the virus ostreid herpesvirus 1 (OsHV-1) and the bacterium Vibrio aestuarianus. Here we describe the interactions between these 2 pathogens and autophagy, a conserved intracellular pathway playing a key role in innate immunity. We show for the first time that autophagy pathway is present and functional in Pacific oysters and plays an important role to protect animals from infections. This study contributes to better understand the innate immune system of Pacific oysters. PMID:25714877

Autophagy plays an important role in protecting Pacific oysters from OsHV-1 and Vibrio aestuarianus infections.

PubMed

Moreau, Pierrick; Moreau, Kevin; Segarra, Amélie; Tourbiez, Delphine; Travers, Marie-Agnès; Rubinsztein, David C; Renault, Tristan

2015-01-01

Recent mass mortality outbreaks around the world in Pacific oysters, Crassostrea gigas, have seriously affected the aquaculture economy. Although the causes for these mortality outbreaks appear complex, infectious agents are involved. Two pathogens are associated with mass mortality outbreaks, the virus ostreid herpesvirus 1 (OsHV-1) and the bacterium Vibrio aestuarianus. Here we describe the interactions between these 2 pathogens and autophagy, a conserved intracellular pathway playing a key role in innate immunity. We show for the first time that autophagy pathway is present and functional in Pacific oysters and plays an important role to protect animals from infections. This study contributes to better understand the innate immune system of Pacific oysters.

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.

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.

The Plasmodium falciparum rhoptry protein RhopH3 plays essential roles in host cell invasion and nutrient uptake

PubMed Central

Sherling, Emma S; Knuepfer, Ellen; Brzostowski, Joseph A; Miller, Louis H; Blackman, Michael J; van Ooij, Christiaan

2017-01-01

Merozoites of the protozoan parasite responsible for the most virulent form of malaria, Plasmodium falciparum, invade erythrocytes. Invasion involves discharge of rhoptries, specialized secretory organelles. Once intracellular, parasites induce increased nutrient uptake by generating new permeability pathways (NPP) including a Plasmodium surface anion channel (PSAC). RhopH1/Clag3, one member of the three-protein RhopH complex, is important for PSAC/NPP activity. However, the roles of the other members of the RhopH complex in PSAC/NPP establishment are unknown and it is unclear whether any of the RhopH proteins play a role in invasion. Here we demonstrate that RhopH3, the smallest component of the complex, is essential for parasite survival. Conditional truncation of RhopH3 substantially reduces invasive capacity. Those mutant parasites that do invade are defective in nutrient import and die. Our results identify a dual role for RhopH3 that links erythrocyte invasion to formation of the PSAC/NPP essential for parasite survival within host erythrocytes. DOI: http://dx.doi.org/10.7554/eLife.23239.001 PMID:28252384

Carotenoid Extraction and Quantification from Capsicum annuum.

PubMed

Richins, Richard D; Kilcrease, James; Rodgriguez-Uribe, Laura; O'Connell, Mary A

2014-10-05

Carotenoids are ubiquitous pigments that play key roles in photosynthesis and also accumulate to high levels in fruit and flowers. Specific carotenoids play essential roles in human health as these compounds are precursors for Vitamin A; other specific carotenoids are important sources of macular pigments and all carotenoids are important anti-oxidants. Accurate determination of the composition and concentration of this complex set of natural products is therefore important in many different scientific areas. One of the richest sources of these compounds is the fruit of Capsicum ; these red, yellow and orange fruit accumulate multiple carotenes and xanthophylls. This report describes the detailed method for the extraction and quantification of specific carotenes and xanthophylls.

Protein-Protein Interactions of Azurin Complex by Coarse-Grained Simulations with a Gō-Like Model

NASA Astrophysics Data System (ADS)

Rusmerryani, Micke; Takasu, Masako; Kawaguchi, Kazutomo; Saito, Hiroaki; Nagao, Hidemi

Proteins usually perform their biological functions by forming a complex with other proteins. It is very important to study the protein-protein interactions since these interactions are crucial in many processes of a living organism. In this study, we develop a coarse grained model to simulate protein complex in liquid system. We carry out molecular dynamics simulations with topology-based potential interactions to simulate dynamical properties of Pseudomonas Aeruginosa azurin complex systems. Azurin is known to play an essential role as an anticancer agent and bind many important intracellular molecules. Some physical properties are monitored during simulation time to get a better understanding of the influence of protein-protein interactions to the azurin complex dynamics. These studies will provide valuable insights for further investigation on protein-protein interactions in more realistic system.

Determination of binding-dioxygen in dioxygen complexes by headspace gas chromatography.

PubMed

Wang, Wei; Feng, Shun; Li, Ya-ni; Wu, Meiying; Wang, Jide

2008-06-06

Dioxygen complexes play important roles in organisms' bodies, so the determination of binding-dioxygen has practical significance. A simple and robust method based on headspace gas chromatography was proposed to determine the binding-dioxygen in dioxygen complexes. By measuring the content change of nitrogen gas in a vial, the amount of oxygen released from dixoygen complexes can be determined. The method was validated using potassium chlorate as model sample, and the results exhibited good recoveries (90-99%) with the relative standard deviation less than 8%. It was also used to analyze dioxygen complex of cobalt bis(salicylaldehyde) ethylenediimine and polyamine cobalt complexes prepared by solid-phase reaction.

Border control: selectivity of chloroplast protein import and regulation at the TOC-complex.

PubMed

Demarsy, Emilie; Lakshmanan, Ashok M; Kessler, Felix

2014-01-01

Plants have evolved complex and sophisticated molecular mechanisms to regulate their development and adapt to their surrounding environment. Particularly the development of their specific organelles, chloroplasts and other plastid-types, is finely tuned in accordance with the metabolic needs of the cell. The normal development and functioning of plastids require import of particular subsets of nuclear encoded proteins. Most preproteins contain a cleavable sequence at their N terminal (transit peptide) serving as a signal for targeting to the organelle and recognition by the translocation machinery TOC-TIC (translocon of outer membrane complex-translocon of inner membrane complex) spanning the dual membrane envelope. The plastid proteome needs constant remodeling in response to developmental and environmental factors. Therefore selective regulation of preprotein import plays a crucial role in plant development. In this review we describe the diversity of transit peptides and TOC receptor complexes, and summarize the current knowledge and potential directions for future research concerning regulation of the different Toc isoforms.

Reliability Standards of Complex Engineering Systems

NASA Astrophysics Data System (ADS)

Galperin, E. M.; Zayko, V. A.; Gorshkalev, P. A.

2017-11-01

Production and manufacture play an important role in today’s modern society. Industrial production is nowadays characterized by increased and complex communications between its parts. The problem of preventing accidents in a large industrial enterprise becomes especially relevant. In these circumstances, the reliability of enterprise functioning is of particular importance. Potential damage caused by an accident at such enterprise may lead to substantial material losses and, in some cases, can even cause a loss of human lives. That is why industrial enterprise functioning reliability is immensely important. In terms of their reliability, industrial facilities (objects) are divided into simple and complex. Simple objects are characterized by only two conditions: operable and non-operable. A complex object exists in more than two conditions. The main characteristic here is the stability of its operation. This paper develops the reliability indicator combining the set theory methodology and a state space method. Both are widely used to analyze dynamically developing probability processes. The research also introduces a set of reliability indicators for complex technical systems.

Literacy as a Leisure Activity: Free-Time Preferences of Older Children and Young Adolescents

ERIC Educational Resources Information Center

Nippold, Marilyn A.; Duthie, Jill K.; Larsen, Jennifer

2005-01-01

Purpose: Literacy plays an important role in the development of language in school-age children and adolescents. For example, by reading a variety of books, magazines, and newspapers, students gain exposure to complex vocabulary, and reading becomes a prime opportunity for learning new words. Despite the importance of reading for lexical …

Elucidation of Enzymatic Mechanism of Phenazine Biosynthetic Protein PhzF Using QM/MM and MD Simulations

PubMed Central

Liu, Fei; Zhao, Yi-Lei; Wang, Xiaolei; Hu, Hongbo; Peng, Huasong; Wang, Wei; Wang, Jing-Fang; Zhang, Xuehong

2015-01-01

The phenazine biosynthetic pathway is of considerable importance for the pharmaceutical industry. The pathway produces two products: phenazine-1,6-dicarboxylic acid and phenazine-1-carboxylic acid. PhzF is an isomerase that catalyzes trans-2,3-dihydro-3-hydroxyanthranilic acid isomerization and plays an essential role in the phenazine biosynthetic pathway. Although the PhzF crystal structure has been determined recently, an understanding of the detailed catalytic mechanism and the roles of key catalytic residues are still lacking. In this study, a computational strategy using a combination of molecular modeling, molecular dynamics simulations, and quantum mechanics/molecular mechanics simulations was used to elucidate these important issues. The Apo enzyme, enzyme–substrate complexes with negatively charged Glu45, enzyme–transition state analog inhibitor complexes with neutral Glu45, and enzyme–product complexes with negatively charged Glu45 structures were optimized and modeled using a 200 ns molecular dynamics simulation. Residues such as Gly73, His74, Asp208, Gly212, Ser213, and water, which play important roles in ligand binding and the isomerization reaction, were comprehensively investigated. Our results suggest that the Glu45 residue at the active site of PhzF acts as a general base/acid catalyst during proton transfer. This study provides new insights into the detailed catalytic mechanism of PhzF and the results have important implications for PhzF modification. PMID:26414009

The complex interplay between macronutrient intake, cuticular hydrocarbon expression and mating success in male decorated crickets.

PubMed

Rapkin, J; Jensen, K; House, C M; Sakaluk, S K; Sakaluk, J K; Hunt, J

2017-04-01

The condition dependence of male sexual traits plays a central role in sexual selection theory. Relatively little, however, is known about the condition dependence of chemical signals used in mate choice and their subsequent effects on male mating success. Furthermore, few studies have isolated the specific nutrients responsible for condition-dependent variation in male sexual traits. Here, we used nutritional geometry to determine the effect of protein (P) and carbohydrate (C) intake on male cuticular hydrocarbon (CHC) expression and mating success in male decorated crickets (Gryllodes sigillatus). We show that both traits are maximized at a moderate-to-high intake of nutrients in a P:C ratio of 1 : 1.5. We also show that female precopulatory mate choice exerts a complex pattern of linear and quadratic sexual selection on this condition-dependent variation in male CHC expression. Structural equation modelling revealed that although the effect of nutrient intake on mating success is mediated through condition-dependent CHC expression, it is not exclusively so, suggesting that other traits must also play an important role. Collectively, our results suggest that the complex interplay between nutrient intake, CHC expression and mating success plays an important role in the operation of sexual selection in G. sigillatus. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

UNIX and healthcare systems: a good marriage.

PubMed

Wieners, W

1992-08-01

Powerful and versatile, UNIX makes open systems affordable in today's complex healthcare marketplace. As more emphasis is placed on combining the best systems for the least money, UNIX plays an important role. How many hospitals are using it already?

Origin of attraction in p-benzoquinone complexes with benzene and p-hydroquinone.

PubMed

Tsuzuki, Seiji; Uchimaru, Tadafumi; Ono, Taizo

2017-08-30

The origin of the attraction in charge-transfer complexes (a p-hydroquinone-p-benzoquinone complex and benzene complexes with benzoquinone, tetracyanoethylene and Br 2 ) was analyzed using distributed multipole analysis and symmetry-adapted perturbation theory. Both methods show that the dispersion interactions are the primary source of the attraction in these charge-transfer complexes followed by the electrostatic interactions. The natures of the intermolecular interactions in these complexes are close to the π/π interactions of neutral aromatic molecules. The electrostatic interactions play important roles in determining the magnitude of the attraction. The contribution of charge-transfer interactions to the attraction is not large compared with the dispersion interactions in these complexes.

Proceedings of the workshop on Cerebellum, Basal Ganglia and Cortical Connections Unmasked in Health and Disorder held in Brno, Czech Republic, October 17th, 2013.

PubMed

Bareš, Martin; Apps, Richard; Kikinis, Zora; Timmann, Dagmar; Oz, Gulin; Ashe, James J; Loft, Michaela; Koutsikou, Stella; Cerminara, Nadia; Bushara, Khalaf O; Kašpárek, Tomáš

2015-04-01

The proceedings of the workshop synthesize the experimental, preclinical, and clinical data suggesting that the cerebellum, basal ganglia (BG), and their connections play an important role in pathophysiology of various movement disorders (like Parkinson's disease and atypical parkinsonian syndromes) or neurodevelopmental disorders (like autism). The contributions from individual distinguished speakers cover the neuroanatomical research of complex networks, neuroimaging data showing that the cerebellum and BG are connected to a wide range of other central nervous system structures involved in movement control. Especially, the cerebellum plays a more complex role in how the brain functions than previously thought.

Effects of Spatial Scale on Cognitive Play in Preschool Children.

ERIC Educational Resources Information Center

Delong, Alton J.; And Others

1994-01-01

Examined effects of a reduced-scale play environment on the temporal aspects of complex play behavior. Children playing with playdough in a 7 x 5 x 5-foot structure began complex play more quickly, played in longer segments, and spent slightly more time in complex play than when in full-size conditions, suggesting that scale-reduced environments…

Exploring children's seasonal play to promote active lifestyles in Auckland, New Zealand.

PubMed

Ergler, Christina R; Kearns, Robin; Witten, Karen

2016-09-01

Studies of seasonal barriers for outdoor activities seldom view families' play practices as grounded in the everyday experience of the natural elements. This paper brings 20 families' mundane outdoor play experiences in Auckland's temperate climate to the fore. Through drawings and interviews, families residing in both suburban detached houses and central city apartments revealed locally constituted beliefs about appropriate play spaces (e.g. garden, park). While the majority of participants retreated to indoor activities during winter, some children and their parents viewed the outdoors as the only opportunity for 'real fun'. We advocate the importance of a better understanding of children's seasonal outdoor play. In particular, we argue that in order to promote year-round healthy levels of outdoor activities it is necessary to understand variations in societal, neighbourhood and family values attributed to outdoor activities. Further, to develop a more nuanced understanding of the locational complexities of outdoor play it is important to understand the meanings of, and practices associated with, seasonal and weather conditions in different international locations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetics Home Reference: hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome

MedlinePlus

... one component of a protein called type IV collagen . Type IV collagen molecules attach to each other to form complex ... and support cells in many tissues. Type IV collagen networks play an important role in the basement ...

Oligomerization of G protein-coupled receptors: computational methods.

PubMed

Selent, J; Kaczor, A A

2011-01-01

Recent research has unveiled the complexity of mechanisms involved in G protein-coupled receptor (GPCR) functioning in which receptor dimerization/oligomerization may play an important role. Although the first high-resolution X-ray structure for a likely functional chemokine receptor dimer has been deposited in the Protein Data Bank, the interactions and mechanisms of dimer formation are not yet fully understood. In this respect, computational methods play a key role for predicting accurate GPCR complexes. This review outlines computational approaches focusing on sequence- and structure-based methodologies as well as discusses their advantages and limitations. Sequence-based approaches that search for possible protein-protein interfaces in GPCR complexes have been applied with success in several studies, but did not yield always consistent results. Structure-based methodologies are a potent complement to sequence-based approaches. For instance, protein-protein docking is a valuable method especially when guided by experimental constraints. Some disadvantages like limited receptor flexibility and non-consideration of the membrane environment have to be taken into account. Molecular dynamics simulation can overcome these drawbacks giving a detailed description of conformational changes in a native-like membrane. Successful prediction of GPCR complexes using computational approaches combined with experimental efforts may help to understand the role of dimeric/oligomeric GPCR complexes for fine-tuning receptor signaling. Moreover, since such GPCR complexes have attracted interest as potential drug target for diverse diseases, unveiling molecular determinants of dimerization/oligomerization can provide important implications for drug discovery.

Drainage isolation and climate change-driven population expansion shape the genetic structures of Tuber indicum complex in the Hengduan Mountains region.

PubMed

Feng, Bang; Zhao, Qi; Xu, Jianping; Qin, Jiao; Yang, Zhu L

2016-02-24

The orogenesis of the Qinghai-Tibetan Plateau and the Quaternary climate changes have played key roles in driving the evolution of flora and fauna in Southwest China, but their effects on higher fungi are poorly addressed. In this study, we investigated the phylogeographic pattern of the Tuber indicum species complex, an economically important fungal group distributed in the Hengduan Mountains region. Our data confirmed the existence of two distinct lineages, T. indicum and T. himalayense, within this species complex. Three geographic groups (Groups W, N and C) were revealed within T. indicum, with Group W found in the paleo-Lancang River region, while Groups N and C corresponded to the two banks along the contemporary Jinsha River, suggesting that rivers have acted as barriers for gene flow among populations from different drainages. Historical range expansion resulted from climate changes was inferred in Group C, contributing to the observed gene flow among geographic populations within this group. Although no significant geographic structure was identified in T. himalayense, evidence of drainage isolation for this species was also detected. Our findings demonstrate that both topographic changes and Quaternary climate oscillations have played important roles in driving the genetic structures of the T. indicum species complex.

The Nucleosome Remodeling and Deacetylase (NuRD) Complex in Development and Disease

PubMed Central

Basta, Jeannine; Rauchman, Michael

2014-01-01

The Nucleosome Remodeling and Deacetylase (NuRD) complex is one of the major chromatin remodeling complexes found in cells. It plays an important role in regulating gene transcription, genome integrity and cell cycle progression. Through its impact on these basic cellular processes, increasing evidence indicates that alterations in the activity of this macromolecular complex can lead to developmental defects, oncogenesis and accelerated ageing. Recent genetic and biochemical studies have elucidated the mechanisms of NuRD action in modifying the chromatin landscape. These advances have the potential to lead to new therapeutic approaches to birth defects and cancer. PMID:24880148

Resultant as the determinant of a Koszul complex

NASA Astrophysics Data System (ADS)

Anokhina, A. S.; Morozov, A. Yu.; Shakirov, Sh. R.

2009-09-01

The determinant is a very important characteristic of a linear map between vector spaces. Two generalizations of linear maps are intensively used in modern theory: linear complexes (nilpotent chains of linear maps) and nonlinear maps. The determinant of a complex and the resultant are then the corresponding generalizations of the determinant of a linear map. It turns out that these two quantities are related: the resultant of a nonlinear map is the determinant of the corresponding Koszul complex. We give an elementary introduction into these notions and relations, which will definitely play a role in the future development of theoretical physics.

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.

Simulations of Instabilities in Complex Valve and Feed Systems

NASA Technical Reports Server (NTRS)

Ahuja, Vineet; Hosangadi, Ashvin; Shipman, Jeremy; Cavallo, Peter A.

2006-01-01

CFD analyses are playing an increasingly important role in identifying and characterizing flow induced instabilities in rocket engine test facilities and flight systems. In this paper, we analyze instability mechanisms that range from turbulent pressure fluctuations due to vortex shedding in structurally complex valve systems to flow resonance in plug cavities to large scale pressure fluctuations due to collapse of cavitation induced vapor clouds. Furthermore, we discuss simulations of transient behavior related to valve motion that can serve as guidelines for valve scheduling. Such predictions of valve response to varying flow conditions is of crucial importance to engine operation and testing.

Development of the Cellular Immune System of Drosophila Requires the Membrane Attack Complex/Perforin-Like Protein Torso-Like.

PubMed

Forbes-Beadle, Lauren; Crossman, Tova; Johnson, Travis K; Burke, Richard; Warr, Coral G; Whisstock, James C

2016-10-01

Pore-forming members of the membrane attack complex/perforin-like (MACPF) protein superfamily perform well-characterized roles as mammalian immune effectors. For example, complement component 9 and perforin function to directly form pores in the membrane of Gram-negative pathogens or virally infected/transformed cells, respectively. In contrast, the only known MACPF protein in Drosophila melanogaster, Torso-like, plays crucial roles during development in embryo patterning and larval growth. Here, we report that in addition to these functions, Torso-like plays an important role in Drosophila immunity. However, in contrast to a hypothesized effector function in, for example, elimination of Gram-negative pathogens, we find that torso-like null mutants instead show increased susceptibility to certain Gram-positive pathogens such as Staphylococcus aureus and Enterococcus faecalis We further show that this deficit is due to a severely reduced number of circulating immune cells and, as a consequence, an impaired ability to phagocytose bacterial particles. Together these data suggest that Torso-like plays an important role in controlling the development of the Drosophila cellular immune system. Copyright © 2016 by the Genetics Society of America.

Modeling infectious diseases dissemination through online role-playing games.

PubMed

Balicer, Ran D

2007-03-01

As mathematical modeling of infectious diseases becomes increasingly important for developing public health policies, a novel platform for such studies might be considered. Millions of people worldwide play interactive online role-playing games, forming complex and rich networks among their virtual characters. An unexpected outbreak of an infective communicable disease (unplanned by the game creators) recently occurred in this virtual world. This outbreak holds surprising similarities to real-world epidemics. It is possible that these virtual environments could serve as a platform for studying the dissemination of infectious diseases, and as a testing ground for novel interventions to control emerging communicable diseases.

[MusicPlayTherapy--a parent-child psychotherapy for children 0-4 years old].

PubMed

Stumptner, Katrin; Thomsen, Cornelia

2005-10-01

The early stage of building up the parent-child relationship is especially important. It is the basis for the child's development of the ability to relate to others and his or her further emotional, social and cognitive development. In this important early phase various risk factors may alienate parents from their intuitive parental competence towards their children. Such interaction problems indicate an intervention in the form of parent-children psychotherapy. This constitutes an entry point for the concept of MusicPlayTherapy (MPT): The early relationship is characterized mainly by complex communication sequences that address the senses at all levels. Therefore, the MPT concept integrates music as medium to communicate and opens up a playing space for play that allows emotions and experiences to be expressed. The components of music such as rhythm, sound, and melody stimulate babies and toddlers to express, play, and communicate preverbally. We work with the child and a parent in the MusicPlayTherapy sessions. Parents learn again to play and thereby learn to reach their children emotionally and to communicate with them. We complement the therapy sessions by counselling sessions with both parents.

A spectral method for spatial downscaling

EPA Science Inventory

Complex computer models play a crucial role in air quality research. These models are used to evaluate potential regulatory impacts of emission control strategies and to estimate air quality in areas without monitoring data. For both of these purposes, it is important to calibrat...

The importance of ligand speciation in environmental research: a case study.

PubMed

Sillanpää, M; Orama, M; Rämö, J; Oikari, A

2001-02-21

The speciations of EDTA and DTPA in process, waste and river waters are modelled and simulated, specifically to the mode of occurrence in the pulp and paper mill effluents and subsequently in receiving waters. Due to relatively short residence times in bleaching process and waste water treatment and slow exchange kinetics, it is expected that the thermodynamic equilibrium is not necessarily reached. Therefore, the initial speciation plays a key role. As such, the simulations have been extended to the process waters of the pulp and paper industry taking into account estimated average conditions. The results reveal that the main species are; Mn and Ca complexes of EDTA and DTPA in pulp mill process waters; Fe(III) and Mn complexes of EDTA and DTPA in waste waters; Fe(III) and Zn complexes of EDTA and DTPA in receiving waters. It is also shown how the increasing concentration of complexing agents effects the speciation. Alkaline earth metal chelation plays a significant role in the speciation of EDTA and DTPA when there is a noticeable molar excess of complexing agents compared with transition metals.

Robust and stretchable indium gallium zinc oxide-based electronic textiles formed by cilia-assisted transfer printing

PubMed Central

Yoon, Jongwon; Jeong, Yunkyung; Kim, Heeje; Yoo, Seonggwang; Jung, Hoon Sun; Kim, Yonghun; Hwang, Youngkyu; Hyun, Yujun; Hong, Woong-Ki; Lee, Byoung Hun; Choa, Sung-Hoon; Ko, Heung Cho

2016-01-01

Electronic textile (e-textile) allows for high-end wearable electronic devices that provide easy access for carrying, handling and using. However, the related technology does not seem to be mature because the woven fabric hampers not only the device fabrication process directly on the complex surface but also the transfer printing of ultrathin planar electronic devices. Here we report an indirect method that enables conformal wrapping of surface with arbitrary yet complex shapes. Artificial cilia are introduced in the periphery of electronic devices as adhesive elements. The cilia also play an important role in confining a small amount of glue and damping mechanical stress to maintain robust electronic performance under mechanical deformation. The example of electronic applications depicts the feasibility of cilia for ‘stick-&-play' systems, which provide electronic functions by transfer printing on unconventional complex surfaces. PMID:27248982

Multi-scale Modeling and Analysis of Nano-RFID Systems on HPC Setup

NASA Astrophysics Data System (ADS)

Pathak, Rohit; Joshi, Satyadhar

In this paper we have worked out on some the complex modeling aspects such as Multi Scale modeling, MATLAB Sugar based modeling and have shown the complexities involved in the analysis of Nano RFID (Radio Frequency Identification) systems. We have shown the modeling and simulation and demonstrated some novel ideas and library development for Nano RFID. Multi scale modeling plays a very important role in nanotech enabled devices properties of which cannot be explained sometimes by abstraction level theories. Reliability and packaging still remains one the major hindrances in practical implementation of Nano RFID based devices. And to work on them modeling and simulation will play a very important role. CNTs is the future low power material that will replace CMOS and its integration with CMOS, MEMS circuitry will play an important role in realizing the true power in Nano RFID systems. RFID based on innovations in nanotechnology has been shown. MEMS modeling of Antenna, sensors and its integration in the circuitry has been shown. Thus incorporating this we can design a Nano-RFID which can be used in areas like human implantation and complex banking applications. We have proposed modeling of RFID using the concept of multi scale modeling to accurately predict its properties. Also we give the modeling of MEMS devices that are proposed recently that can see possible application in RFID. We have also covered the applications and the advantages of Nano RFID in various areas. RF MEMS has been matured and its devices are being successfully commercialized but taking it to limits of nano domains and integration with singly chip RFID needs a novel approach which is being proposed. We have modeled MEMS based transponder and shown the distribution for multi scale modeling for Nano RFID.

Border control: selectivity of chloroplast protein import and regulation at the TOC-complex

PubMed Central

Demarsy, Emilie; Lakshmanan, Ashok M.; Kessler, Felix

2014-01-01

Plants have evolved complex and sophisticated molecular mechanisms to regulate their development and adapt to their surrounding environment. Particularly the development of their specific organelles, chloroplasts and other plastid-types, is finely tuned in accordance with the metabolic needs of the cell. The normal development and functioning of plastids require import of particular subsets of nuclear encoded proteins. Most preproteins contain a cleavable sequence at their N terminal (transit peptide) serving as a signal for targeting to the organelle and recognition by the translocation machinery TOC–TIC (translocon of outer membrane complex–translocon of inner membrane complex) spanning the dual membrane envelope. The plastid proteome needs constant remodeling in response to developmental and environmental factors. Therefore selective regulation of preprotein import plays a crucial role in plant development. In this review we describe the diversity of transit peptides and TOC receptor complexes, and summarize the current knowledge and potential directions for future research concerning regulation of the different Toc isoforms. PMID:25278954

The structure and function of Alzheimer's gamma secretase enzyme complex.

PubMed

Krishnaswamy, Sudarsan; Verdile, Giuseppe; Groth, David; Kanyenda, Limbikani; Martins, Ralph N

2009-01-01

The production and accumulation of the beta amyloid protein (Abeta) is a key event in the cascade of oxidative and inflammatory processes that characterizes Alzheimer's disease (AD). A multi-subunit enzyme complex, referred to as gamma (gamma) secretase, plays a pivotal role in the generation of Abeta from its parent molecule, the amyloid precursor protein (APP). Four core components (presenilin, nicastrin, aph-1, and pen-2) interact in a high-molecular-weight complex to perform intramembrane proteolysis on a number of membrane-bound proteins, including APP and Notch. Inhibitors and modulators of this enzyme have been assessed for their therapeutic benefit in AD. However, although these agents reduce Abeta levels, the majority have been shown to have severe side effects in pre-clinical animal studies, most likely due to the enzymes role in processing other proteins involved in normal cellular function. Current research is directed at understanding this enzyme and, in particular, at elucidating the roles that each of the core proteins plays in its function. In addition, a number of interacting proteins that are not components of gamma-secretase also appear to play important roles in modulating enzyme activity. This review will discuss the structural and functional complexity of the gamma-secretase enzyme and the effects of inhibiting its activity.

Ironing out the role of the cyclin-dependent kinase inhibitor, p21 in cancer: Novel iron chelating agents to target p21 expression and activity.

PubMed

Moussa, Rayan S; Park, Kyung Chan; Kovacevic, Zaklina; Richardson, Des R

2018-03-20

Iron (Fe) has become an important target for the development of anti-cancer therapeutics with a number of Fe chelators entering human clinical trials for advanced and resistant cancer. An important aspect of the activity of these compounds is their multiple molecular targets, including those that play roles in arresting the cell cycle, such as the cyclin-dependent kinase inhibitor, p21. At present, the exact mechanism by which Fe chelators regulate p21 expression remains unclear. However, recent studies indicate the ability of chelators to up-regulate p21 at the mRNA level was dependent on the chelator and cell-type investigated. Analysis of the p21 promoter identified that the Sp1-3-binding site played a significant role in the activation of p21 transcription by Fe chelators. Furthermore, there was increased Sp1/ER-α and Sp1/c-Jun complex formation in melanoma cells, suggesting these complexes were involved in p21 promoter activation. Elucidating the mechanisms involved in the regulation of p21 expression in response to Fe chelator treatment in neoplastic cells will further clarify how these agents achieve their anti-tumor activity. It will also enhance our understanding of the complex roles p21 may play in neoplastic cells and lead to the development of more effective and specific anti-cancer therapies. Copyright © 2018 Elsevier Inc. All rights reserved.

NATURE OF CUMULATIVE IMPACTS ON BIOTIC DIVERSITY OF WETLAND VERTEBRATES

EPA Science Inventory

There is no longer any doubt that cumulative impacts have important effects on wetland vertebrates. he interactions of species diversity and community structure produce a complex pattern in which environmental impacts can play a highly significant role. ariety of examples shows h...

Morphological and Physiological Alteration of Maize Root Architectures on Drought Stress.

USDA-ARS?s Scientific Manuscript database

Drought tolerance is a complex agronomic trait and root characteristics logically play an important role in determining the response of plants to drought stress. Research experiments were conducted to investigate genotypic variations in morphological and physiological responses of roots to drought s...

Gas-phase chemical kinetics: Three is the magic number

NASA Astrophysics Data System (ADS)

Skodje, Rex T.

2017-11-01

Although predicted many years ago, chemically reactive termolecular reactions were thought to be unimportant in defining the behaviour of combustion systems. Now, calculations have shown that such reactions between radicals and long-lived bimolecular complexes can actually play an important role in hydrogen combustion.

High Abundance of Ions in Cosmic Ices

NASA Technical Reports Server (NTRS)

Gudipati, Murthy S.; Allamandola, Louis J.; Fonda, Mark (Technical Monitor)

2002-01-01

Water-rich, mixed molecular ices and polycyclic aromatic hydrocarbons (PAHs) are common throughout interstellar molecular clouds and the Solar System. Vacuum ultraviolet (VUV) irradiation and particle bombardment of these abiotic ices produces complex organic species, including important biogenic molecules such as amino acids and functionalized PAHs which may have played a role in the origin of life. This ability of such water-rich, oxygen dominated ices to promote production of complex organic species is surprising and points to an important, unusual, but previously overlooked mechanism at play within the ice. Here we report the nature of this mechanism using electronic spectroscopy. VUV-irradiation of PAH/H2O ices leads to an unprecedented and efficient (greater than 70 %) conversion of the neutral PAHs to their cation form (PAH+). Further, these H2O/PAH+ ices are stabile at temperatures below 50 K, a temperature domain common throughout interstellar clouds and the Solar System. Between 50 and 125 K they react to form the complex organics. In view of this, we conclude that charged PAHs and other molecular ions should be common and abundant in many cosmic ices. The chemical, spectroscopic and physical properties of these ion-rich ices can be of fundamental importance for objects as diverse as comets, planets, and molecular clouds and may account for several poorly understood phenomena associated with each of these object classes.

Differential regulation of the transcriptional activity of the glucocorticoid receptor through site-specific phosphorylation.

PubMed

Kumar, Raj; Calhoun, William J

2008-12-01

Post-translational modifications such as phosphorylation are known to play an important role in the gene regulation by the transcription factors including the nuclear hormone receptor superfamily of which the glucocorticoid receptor (GR) is a member. Protein phosphorylation often switches cellular activity from one state to another. Like many other transcription factors, the GR is a phosphoprotein, and phosphorylation plays an important role in the regulation of GR activity. Cell signaling pathways that regulate phosphorylation of the GR and its associated proteins are important determinants of GR function under various physiological conditions. While the role of many phosphorylation sites in the GR is still not fully understood, the role of others is clearer. Several aspects of transcription factor function, including DNA binding affinity, interaction of transactivation domains with the transcription initiation complex, and shuttling between the cytoplasmic compartments, have all been linked to site-specific phosphorylation. All major phosphorylation sites in the human GR are located in the N-terminal domain including the major transactivation domain, AF1. Available literature clearly indicates that many of these potential phosphorylation sites are substrates for multiple kinases, suggesting the potential for a very complex regulatory network. Phosphorylated GR interacts favorably with critical coregulatory proteins and subsequently enhances transcriptional activity. In addition, the activities and specificities of coregulators may be subject to similar regulation by phosphorylation. Regulation of the GR activity due to phosphorylation appears to be site-specific and dependent upon specific cell signaling cascade. Taken together, site-specific phosphorylation and related kinase pathways play an important role in the action of the GR, and more precise mechanistic information will lead to fuller understanding of the complex nature of gene regulation by the GR- and related transcription factors. This review provides currently available information regarding the role of GR phosphorylation in its action, and highlights the possible underlying mechanisms of action.

Verbal play as a discourse resource in the social interactions of older and younger communication pairs.

PubMed

Shune, Samantha; Duff, Melissa Collins

2014-01-01

Verbal play, or the playful manipulation of elements of language, is a pervasive component of social interaction, serving important interpersonal functions. We analyzed verbal play in the interactional discourse of ten healthy younger pairs and ten healthy older pairs as they completed a collaborative referencing task. A total of 1,893 verbal play episodes were coded. While there were no group differences in verbal play frequency, age-related differences in the quality and function of these episodes emerged. While older participants engaged in more complex, extended, and reciprocal episodes that supported the social nature of communicative interactions (e.g., teasing), younger participants were more likely to engage in verbal play episodes for the purpose of successful task completion. Despite these age-related variations in the deployment of verbal play, verbal play is a robust interactional discourse resource in healthy aging, highlighting an element of human cognition that does not appear to decline with age.

Verbal play as a discourse resource in the social interactions of older and younger communication pairs

PubMed Central

Shune, Samantha; Duff, Melissa Collins

2014-01-01

Verbal play, or the playful manipulation of elements of language, is a pervasive component of social interaction, serving important interpersonal functions. We analyzed verbal play in the interactional discourse of ten healthy younger pairs and ten healthy older pairs as they completed a collaborative referencing task. A total of 1,893 verbal play episodes were coded. While there were no group differences in verbal play frequency, age-related differences in the quality and function of these episodes emerged. While older participants engaged in more complex, extended, and reciprocal episodes that supported the social nature of communicative interactions (e.g., teasing), younger participants were more likely to engage in verbal play episodes for the purpose of successful task completion. Despite these age-related variations in the deployment of verbal play, verbal play is a robust interactional discourse resource in healthy aging, highlighting an element of human cognition that does not appear to decline with age. PMID:25485072

Complex Relationships Between Food, Diet and the Microbiome

PubMed Central

Pace, Laura A.; Crowe, Sheila E.

2018-01-01

Diet is a risk factor in a number of medically important disease states including obesity, celiac disease and functional gastrointestinal disorders. Modification of diet can prevent, treat or alleviate some of the symptoms associated with these diseases and improve general health. It is important to provide patients with simple dietary recommendations in order to increase the probability of successful implementation. These include increasing vegetable, fruit and fiber intake, consuming lean protein sources to enhance satiety, avoiding or severely limiting highly processed foods, and reducing portion sizes for overweight and obese patients. Women can play an important role in maintaining family health by making more informed dietary decisions. The gut microbiome may play a role in some gastrointestinal disorders. However better designed studies are required to differentiate correlation from causation in this emerging area. PMID:27261897

Complexity and Control: The Organisational Background of Credentialism.

ERIC Educational Resources Information Center

Tyler, William

1982-01-01

Examines the role of organizational processes in generating the demand for qualified personnel. Neo-Weberian theorists point to the importance of contextual features of organizations such as size and national prominence as predictors of educational demand. Neo-Marxist historians examine the role played by credentials. (AM)

Carbon Sequestration in Wetland Soils of the Northern Gulf of Mexico Coastal Region

EPA Science Inventory

Coastal wetlands play an important but complex role in the global carbon cycle, contributing to the ecosystem service of greenhouse gas regulation through carbon sequestration. Although coastal wetlands occupy a small percent of the total US land area, their potential for carbon...

Morphological and Biological alteration of maize root architectures on drought stress

USDA-ARS?s Scientific Manuscript database

Drought tolerance is a complex agronomic trait and root characteristics logically play an important role in determining the response of plants to drought stress. Studies were conducted to investigate genotypic variations in morphological and physiological responses of roots to drought stress in corn...

Morphological and biological alteration of maize root architectures on drought stress

USDA-ARS?s Scientific Manuscript database

Drought tolerance is a complex agronomic trait and root characteristics logically play an important role in determining the response of plants to drought stress. Studies were conducted to investigate genotypic variations in morphological and physiological responses of roots to drought stress in corn...

Levels of Discourse in Psychotherapeutic Interactions.

ERIC Educational Resources Information Center

Smolucha, Larry Walter

Speech plays important and complex roles in self-regulation and is experienced in several distinct forms: as a social-discursive mode of communication and direction (social speech), as vocalizations directed to the self rather than to others (private speech), and as the phenomenologically subjective "interior dialogue" through which the…

Satellite observation of particulate organic carbon dynamics on the Louisiana continental shelf

EPA Science Inventory

Particulate organic carbon (POC) plays an important role in coastal carbon cycling and the formation of hypoxia. Yet, coastal POC dynamics are often poorly understood due to a lack of long-term POC observations and the complexity of coastal hydrodynamic and biogeochemical process...

[Pay attention to the imaging diagnosis of complex anal fistula].

PubMed

Zhou, Zhiyang

2015-12-01

The diagnosis and treatment of complex anal fistula has been a significant challenge. Unwise incision and excessive exploration will lead to the secondary branch, sinus and perforation. A simple fistula may become a surgical problem and result in disastrous consequences. Preoperative accurate diagnosis of anal fistula, including in the internal opening, primary track and location of the fistula, extensions and abscess, is important for anal fistula treatment. In the diagnosis of anal fistula, imaging examination, especially MRI plays a crucial role. Localization and demarcation of anal fistula and the relationship with sphincter are important. MRI has been an indispensable confirmatory imaging examination.

Music cognition and the cognitive sciences.

PubMed

Pearce, Marcus; Rohrmeier, Martin

2012-10-01

Why should music be of interest to cognitive scientists, and what role does it play in human cognition? We review three factors that make music an important topic for cognitive scientific research. First, music is a universal human trait fulfilling crucial roles in everyday life. Second, music has an important part to play in ontogenetic development and human evolution. Third, appreciating and producing music simultaneously engage many complex perceptual, cognitive, and emotional processes, rendering music an ideal object for studying the mind. We propose an integrated status for music cognition in the Cognitive Sciences and conclude by reviewing challenges and big questions in the field and the way in which these reflect recent developments. Copyright © 2012 Cognitive Science Society, Inc.

Multiple Export Mechanisms for mRNAs

PubMed Central

Delaleau, Mildred; Borden, Katherine L. B.

2015-01-01

Nuclear mRNA export plays an important role in gene expression. We describe the mechanisms of mRNA export including the importance of mRNP assembly, docking with the nuclear basket of the nuclear pore complex (NPC), transit through the central channel of the NPC and cytoplasmic release. We describe multiple mechanisms of mRNA export including NXF1 and CRM1 mediated pathways. Selective groups of mRNAs can be preferentially transported in order to respond to cellular stimuli. RNAs can be selected based on the presence of specific cis-acting RNA elements and binding of specific adaptor proteins. The role that dysregulation of this process plays in human disease is also discussed. PMID:26343730

Chemical bonding in silicon-carbene complexes.

PubMed

Liu, Z

2009-06-04

The bonding situations in the newly synthesized silicon-carbene complexes with formulas L:SiCl4, L:(Cl)Si-Si(Cl):L, and L:Si=Si:L (where L: is an N-heterocyclic carbene), are reported using density functional theory at the BP86/TZ2P level. The bonding analysis clearly shows that the bonding situation in the silicon-carbene complexes cannot be described in terms of donor-acceptor interactions depicted in the Dewar-Chatt-Duncanson model. The energy decomposition analysis (EDA) shows that the electrostatic attraction plays an important or even dominant role for the Si-C(carbene) binding interactions in the silicon-carbene complexes. That the molecular orbitals of the silicon-carbene complexes are lower in energy than the parent orbitals of carbenes indicates that these complexes are better described as stabilized carbene complexes.

The role of timbre in pitch matching abilities and pitch discrimination abilities with complex tones

NASA Astrophysics Data System (ADS)

Moore, Robert E.; Watts, Christopher R.; Zhang, Fawen

2004-05-01

Control of fundamental frequency (F0) is important for singing in-tune and is an important factor related to the perception of a talented singing voice. One purpose of the present study was to investigate the relationship between pitch-matching skills, which is one method of testing F0 control, and pitch discrimination skills. It was observed that there was a relationship between pitch matching abilities and pitch discrimination abilities. Those subjects that were accurate pitch matchers were also accurate pitch discriminators (and vice versa). Further, timbre differences appeared to play a role in pitch discrimination accuracy. A second part of the study investigated the effect of timbre on speech discrimination. To study this, all but the first five harmonics of complex tones with different timbre were removed for the pitch discrimination task, thus making the tones more similar in timbre. Under this condition no difference was found between the pitch discrimination abilities of those who were accurate pitch matchers and those who were inaccurate pitch matchers. The results suggest that accurate F0 control is at least partially dependent on pitch discrimination abilities, and timbre appears to play an important role in differences in pitch discrimination ability.

Polyphenol-aluminum complex formation: Implications for aluminum tolerance in plants

USDA-ARS?s Scientific Manuscript database

Natural polyphenols may play an important role in aluminum detoxification in some plants. We examined the interaction between Al3+ and the purified high molecular weight polyphenols pentagalloyl glucose (940 Da) and oenothein B (1568 Da), and the related compound methyl gallate (184 Da) at pH 4 and ...

Tangible Technology-Enhanced Learning for Improvement of Student Collaboration

ERIC Educational Resources Information Center

Barneva, Reneta P.; Gelsomini, Federico; Kanev, Kamen; Bottoni, Paolo

2018-01-01

Collaboration among students in the course of learning plays an important role in developing communication skills. In particular, it helps for team building and brainstorming on solutions of complex problems. While an effective group organization is critical for the success of such collaborative learning, many instructors would make arbitrary…

Data Management Consulting at the Johns Hopkins University

ERIC Educational Resources Information Center

Varvel, Virgil E., Jr.; Shen, Yi

2013-01-01

As research data complexity and quantity grows and funding agency requirements for data management are articulated, there is a growing need for data management services (DMS). Within these services, one important role emerging is that of data management consultant (DMC). Roles were analyzed that these professionals play through case study analysis…

Biodiversity in the city: key challenges for urban green space management

Treesearch

Myla F.J. Aronson; Christopher A. Lepczyk; Karl L. Evans; Mark A. Goddard; Susannah B. Lerman; J. Scott MacIvor; Charles H. Nilon; Timothy Vargo

2017-01-01

Cities play important roles in the conservation of global biodiversity, particularly through the planning and management of urban green spaces (UGS). However, UGS management is subject to a complex assortment of interacting social, cultural, and economic factors, including governance, economics, social networks, multiple stakeholders, individual preferences, and social...

Natural products as inspiration for the development of new synthetic methods.

PubMed

Ma, Zhiqiang; Chen, Chuo

2018-01-01

Natural products have played an important role in shaping modern synthetic organic chemistry. In particular, their complex molecular skeletons have stimulated the development of many new synthetic methods. We highlight in this article some recent examples of synthetic design inspired by the biosynthesis of natural products.

Vaccination of white-tailed deer (Odocoileus virginianus) for protection against bovine tuberculosis

USDA-ARS?s Scientific Manuscript database

Bovine tuberculosis (bTB), caused by Mycobacterium bovis and other related species in the M. tuberculosis complex, pose a serious continual threat to the health and economic wellbeing of wildlife, livestock, and humans worldwide. Wildlife reservoirs of bTB play a very important role in the epidemio...

7-Day Biodefense: Engineered Nanoparticle for Virus Elimination by Opsonization (ENVELOP)

DTIC Science & Technology

2013-12-10

spectrum for LSTc, specifically the identity of the four distinct monosaccharides and the presence of 2→6 sialic acid at stoichimetric levels. 7-Day...A. Previous studies definitively demonstrated that cell surface heparan sulfate, a complex highly charged polysaccharide , plays an important role in

Witnessing versus Experiencing Direct Violence in Childhood as Correlates of Adulthood PTSD

ERIC Educational Resources Information Center

Kulkarni, Madhur R.; Graham-Bermann, Sandra; Rauch, Sheila A. M.; Seng, Julia

2011-01-01

Research has established that childhood violence exposure plays a considerable role in the development of deleterious outcomes in childhood and adulthood. However, important gaps remain in understanding the complex relationships between early violence exposure, adulthood trauma exposure, and posttraumatic stress disorder (PTSD). This study…

Difference in volatile profile between pericarp tissue and locular gel in tomato fruit

USDA-ARS?s Scientific Manuscript database

Aroma, a complex mixture of volatile compounds, plays an important role in the perception and acceptability of tomato products by consumers. Numerous studies have reported volatile profiles in tomatoes based on measurement of the whole fruit or pericarp tissue, however, little is understood regardin...

Internationalization Remodeled: Definition, Approaches, and Rationales

ERIC Educational Resources Information Center

Knight, Jane

2004-01-01

The world of higher education is changing and the world in which higher education plays a significant role is changing. The international dimension of higher education is becoming increasingly important, complex, and confusing. It is therefore timely to reexamine and update the conceptual frameworks underpinning the notion of inter-nationalization…

Memory: Issues of Import to School Psychologists.

ERIC Educational Resources Information Center

John, Kirk R.

This document defines memory as a complex, interactive process that is a prerequisite for all higher learning. Without intact memory skills, a host of disorders may ensue ranging from mild learning problems to disorientation and helplessness (Lezak, 1983). Because of the pervasive and central role memory plays in people's lives, school…

Educational Opportunity and Immigration in México: Exploring the Individual and Systemic Relationships

ERIC Educational Resources Information Center

Martínez, José Felipe; Santibanez, Lucrecia; Serván Mori, Edson E.

2013-01-01

Background/Context: Much research has investigated the complex interplay between education and migration. Education has been alternatively conceptualized as playing an important role as motivator or deterrent of future migration. This relationship, however, is often investigated in terms of coarse indicators of educational attainment. Purpose: In…

[Shoulder injuries in golf].

PubMed

Liem, D; Gosheger, G; Schmidt, C

2014-03-01

Due to its growing popularity golf has now come into the focus of orthopedic sports medicine. With a wide range of age groups and playing levels, orthopedic surgeons will encounter a wide range of musculoskeletal problems which are usually the result of overuse rather than trauma. The shoulder joint plays an important role in the golf swing whereby not only the muscles around the glenohumeral joint but also the scapula stabilizing muscles are extremely important for an effective golf swing. Golf is strictly not considered to be an overhead sport; however, the extreme peak positions of the golf swing involve placing the shoulder joint in maximum abduction and adduction positions which can provoke impingement, lesions of the pulley system or even a special form of posterior shoulder instability. Even after complex shoulder operations, such as rotator cuff repair or shoulder arthroplasty, a return to the golf course at nearly the same level of play can be expected.

Photochemical preparation of pyrimidin-2(1H)-ones by rhenium(I) complexes with visible light.

PubMed

Liu, Qiang; Li, Ya-Nan; Zhang, Hui-Hui; Chen, Bin; Tung, Chen-Ho; Wu, Li-Zhu

2011-03-04

With visible light irradiation (λ > 400 nm) of rhenium(I) complexes (P1-P4), a photochemical conversion from 3,4-dihydropyrimidin-2(1H)-ones to pyrimidin-2(1H)-ones at room temperature has been achieved with good to excellent yields in CH(3)CN-H(2)O solution containing CCl(4) and K(2)CO(3). Luminescence quenching study and product analysis reveal that photoinduced electron transfer between rhenium(I) complex P and 3,4-dihydropyrimidin-2(1H)-ones plays an important role in the initial event.

Methylmercury photodegradation in surface water of the Florida Everglades: importance of dissolved organic matter-methylmercury complexation.

PubMed

Tai, Chao; Li, Yanbin; Yin, Yongguang; Scinto, Leonard J; Jiang, Guibin; Cai, Yong

2014-07-01

Photodegradation is the major pathway of methylmercury (MeHg) degradation in many surface waters. However, the mechanism of MeHg photodegradation is still not completely understood. Dissolved organic matter (DOM) is expected to play a critical role in MeHg photodegradation. By using several techniques, including N2/O2 purging and the addition of stable isotope (Me(201)Hg), scavengers, competing ligands, and a singlet oxygen ((1)O2) generator, the role played by MeHg-DOM complexation in MeHg photodegradation of Everglades surface water was investigated. DOM appeared to be involved in MeHg photodegradation via the formation MeHg-DOM complexes based on three findings: (1) MeHg was quickly photodegraded in solutions containing DOM extracts; (2) degradation of MeHg did not occur in deionized water; and (3) addition of competing complexation reagents (dithiothreitol-DTT) dramatically prohibited the photodegradation of MeHg in Everglades water. Further experiments indicated that free radicals/reactive oxygen species, including hydroxyl radical (·OH), (1)O2, triplet excited state of DOM ((3)DOM*), and hydrated electron (e(-)aq), played a minor role in MeHg photodegradation in Everglades water, based on the results of scavenger addition, (1)O2 generator addition and N2/O2 purging. A pathway, involving direct photodegradation of MeHg-DOM complexes via intramolecular electron transfer, is proposed as the dominant mechanism for MeHg photodegradation in Everglades water.

[Noncovalent cation-π interactions--their role in nature].

PubMed

Fink, Krzysztof; Boratyński, Janusz

2014-11-07

Non-covalent interactions play an extremely important role in organisms. The main non-covalent interactions in nature are: ion-ion interactions, dipole-dipole interactions, hydrogen bonds, and van der Waals interactions. A new kind of intermolecular interactions--cation-π interactions--is gaining increasing attention. These interactions occur between a cation and a π system. The main contributors to cation-π interactions are electrostatic, polarization and, to a lesser extent, dispersion interactions. At first, cation-π interactions were studied in a gas phase, with metal cation-aromatic system complexes. The characteristics of these complexes are as follows: an increase of cation atomic number leads to a decrease of interaction energy, and an increase of cation charge leads to an increase of interaction energy. Aromatic amino acids bind with metal cations mainly through interactions with their main chain. Nevertheless, cation-π interaction with a hydrophobic side chain significantly enhances binding energy. In water solutions most cations preferentially interact with water molecules rather than aromatic systems. Cation-π interactions occur in environments with lower accessibility to a polar solvent. Cation-π interactions can have a stabilizing role on the secondary, tertiary and quaternary structure of proteins. These interactions play an important role in substrate or ligand binding sites in many proteins, which should be taken into consideration when the screening of effective inhibitors for these proteins is carried out. Cation-π interactions are abundant and play an important role in many biological processes.

Protein translocation channel of mitochondrial inner membrane and matrix-exposed import motor communicate via two-domain coupling protein.

PubMed

Banerjee, Rupa; Gladkova, Christina; Mapa, Koyeli; Witte, Gregor; Mokranjac, Dejana

2015-12-29

The majority of mitochondrial proteins are targeted to mitochondria by N-terminal presequences and use the TIM23 complex for their translocation across the mitochondrial inner membrane. During import, translocation through the channel in the inner membrane is coupled to the ATP-dependent action of an Hsp70-based import motor at the matrix face. How these two processes are coordinated remained unclear. We show here that the two domain structure of Tim44 plays a central role in this process. The N-terminal domain of Tim44 interacts with the components of the import motor, whereas its C-terminal domain interacts with the translocation channel and is in contact with translocating proteins. Our data suggest that the translocation channel and the import motor of the TIM23 complex communicate through rearrangements of the two domains of Tim44 that are stimulated by translocating proteins.

Food-web complexity, meta-community complexity and community stability.

PubMed

Mougi, A; Kondoh, M

2016-04-13

What allows interacting, diverse species to coexist in nature has been a central question in ecology, ever since the theoretical prediction that a complex community should be inherently unstable. Although the role of spatiality in species coexistence has been recognized, its application to more complex systems has been less explored. Here, using a meta-community model of food web, we show that meta-community complexity, measured by the number of local food webs and their connectedness, elicits a self-regulating, negative-feedback mechanism and thus stabilizes food-web dynamics. Moreover, the presence of meta-community complexity can give rise to a positive food-web complexity-stability effect. Spatiality may play a more important role in stabilizing dynamics of complex, real food webs than expected from ecological theory based on the models of simpler food webs.

Carbon in the Universe

NASA Technical Reports Server (NTRS)

Allamandola, Louis J.

2013-01-01

Over the past few decades, NASA missions have revealed that we live in a Universe that is not a hydrogen-dominated, physicist's paradise, but in a molecular Universe with complex molecules directly interwoven into its fabric. These missions have shown that molecules are an abundant and important component of astronomical objects at all stages of their evolution and that they play a key role in many processes that dominate the structure and evolution of galaxies. Closer to home in our galaxy, the Milky Way, they have revealed a unique and complex organic inventory of regions of star and planet formation that may well represent some of the prebiotic roots to life. Astrobiology emerges from the great interest in understanding astrochemical evolution from simple to complex molecules, especially those with biogenic potential and the roles they may play as primordial seeds in the origin of life on habitable worlds. The first part of this talk will highlight how infrared spectroscopic studies of interstellar space, combined with dedicated laboratory simulations, have revealed the widespread presence of complex organics across deep space. The remainder of the presentation will focus on the evolution of these materials and astrobiology.

Possible roles of two quinone molecules in direct and indirect proton pumps of bovine heart NADH-quinone oxidoreductase (complex I).

PubMed

Ohnishi, S Tsuyoshi; Salerno, John C; Ohnishi, Tomoko

2010-12-01

In many energy transducing systems which couple electron and proton transport, for example, bacterial photosynthetic reaction center, cytochrome bc(1)-complex (complex III) and E. coli quinol oxidase (cytochrome bo(3) complex), two protein-associated quinone molecules are known to work together. T. Ohnishi and her collaborators reported that two distinct semiquinone species also play important roles in NADH-ubiquinone oxidoreductase (complex I). They were called SQ(Nf) (fast relaxing semiquinone) and SQ(Ns) (slow relaxing semiquinone). It was proposed that Q(Nf) serves as a "direct" proton carrier in the semiquinone-gated proton pump (Ohnishi and Salerno, FEBS Letters 579 (2005) 4555), while Q(Ns) works as a converter between one-electron and two-electron transport processes. This communication presents a revised hypothesis in which Q(Nf) plays a role in a "direct" redox-driven proton pump, while Q(Ns) triggers an "indirect" conformation-driven proton pump. Q(Nf) and Q(Ns) together serve as (1e(-)/2e(-)) converter, for the transfer of reducing equivalent to the Q-pool. Copyright © 2010 Elsevier B.V. All rights reserved.

Power distribution in complex environmental negotiations: Does balance matter?

USGS Publications Warehouse

Burkardt, N.; Lamb, B.L.; Taylor, J.G.

1997-01-01

We studied six interagency negotiations covering Federal Energy Regulatory Commission (FERC) hydroelectric power licenses. Negotiations occurred between state and federal resource agencies and developers over project operations and natural resource mitigation. We postulated that a balance of power among parties was necessary for successful negotiations. We found a complex relationship between balanced power and success and conclude that a balance of power was associated with success in these negotiations. Power played a dynamic role in the bargaining and illuminates important considerations for regulatory design.

[Adolescent crises in puberty. Diagnosis and therapy (author's transl)].

PubMed

Müller-Küppers, M

1979-08-24

Psychological disorders which become manifest as adolescent crises must be seen as complex phenomena and treated thoroughly: besides the genetic, biographic and psychosocial background of the youthful individual the cultural and economic aspects play an important role. Nevertheless we must admit that associated causal explanations, e.g. for accelerated or late development are lacking. Focal points for the subsequent symptom complexes of sexual behavior in puberty are: psychosexual prematurity or retardation, masturbation, homosexual relations, pubertal asceticism and premature and frequently changing sexual relations.

The nucleotide exchange factor MGE exerts a key function in the ATP-dependent cycle of mt-Hsp70-Tim44 interaction driving mitochondrial protein import.

PubMed Central

Schneider, H C; Westermann, B; Neupert, W; Brunner, M

1996-01-01

Import of preproteins into the mitochondrial matrix is driven by the ATP-dependent interaction of mt-Hsp70 with the peripheral inner membrane import protein Tim44 and the preprotein in transit. We show that Mge1p, a co-chaperone of mt-Hsp70, plays a key role in the ATP-dependent import reaction cycle in yeast. Our data suggest a cycle in which the mt-Hsp70-Tim44 complex forms with ATP: Mge1p promotes assembly of the complex in the presence of ATP. Hydrolysis of ATP by mt-Hsp70 occurs in complex with Tim44. Mge1p is then required for the dissociation of the ADP form of mt-Hsp70 from Tim44 after release of inorganic phosphate but before release of ADP. ATP hydrolysis and complex dissociation are accompanied by tight binding of mt-Hsp70 to the preprotein in transit. Subsequently, the release of mt-Hsp70 from the polypeptide chain is triggered by Mge1p which promotes release of ADP from mt-Hsp70. Rebinding of ATP to mt-Hsp70 completes the reaction cycle. Images PMID:8918457

The Major Histocompatibility Complex in Bovines: A Review

PubMed Central

Behl, Jyotsna Dhingra; Verma, N. K.; Tyagi, Neha; Mishra, Priyanka; Behl, Rahul; Joshi, B. K.

2012-01-01

Productivity in dairy cattle and buffaloes depends on the genetic factors governing the production of milk and milk constituents as well as genetic factors controlling disease resistance or susceptibility. The immune system is the adaptive defense system that has evolved in vertebrates to protect them from invading pathogens and also carcinomas. It is remarkable in the sense that it is able to generate an enormous variety of cells and biomolecules which interact with each other in numerous ways to form a complex network that helps to recognize, counteract, and eliminate the apparently limitless number of foreign invading pathogens/molecules. The major histocompatibility complex which is found to occur in all mammalian species plays a central role in the development of the immune system. It is an important candidate gene involved in susceptibility/resistance to various diseases. It is associated with intercellular recognition and with self/nonself discrimination. It plays major role in determining whether transplanted tissue will be accepted as self or rejected as foreign. PMID:23738132

Biogenesis of the mitochondrial TOM complex: Mim1 promotes insertion and assembly of signal-anchored receptors.

PubMed

Becker, Thomas; Pfannschmidt, Sylvia; Guiard, Bernard; Stojanovski, Diana; Milenkovic, Dusanka; Kutik, Stephan; Pfanner, Nikolaus; Meisinger, Chris; Wiedemann, Nils

2008-01-04

The translocase of the outer membrane (TOM complex) is the central entry gate for nuclear-encoded mitochondrial precursor proteins. All Tom proteins are also encoded by nuclear genes and synthesized as precursors in the cytosol. The channel-forming beta-barrel protein Tom40 is targeted to mitochondria via Tom receptors and inserted into the outer membrane by the sorting and assembly machinery (SAM complex). A further outer membrane protein, Mim1, plays a less defined role in assembly of Tom40 into the TOM complex. The three receptors Tom20, Tom22, and Tom70 are anchored in the outer membrane by a single transmembrane alpha-helix, located at the N terminus in the case of Tom20 and Tom70 (signal-anchored) or in the C-terminal portion in the case of Tom22 (tail-anchored). Insertion of the precursor of Tom22 into the outer membrane requires pre-existing Tom receptors while the import pathway of the precursors of Tom20 and Tom70 is only poorly understood. We report that Mim1 is required for efficient membrane insertion and assembly of Tom20 and Tom70, but not Tom22. We show that Mim1 associates with SAM(core) components to a large SAM complex, explaining its role in late steps of the assembly pathway of Tom40. We conclude that Mim1 is not only required for biogenesis of the beta-barrel protein Tom40 but also for membrane insertion and assembly of signal-anchored Tom receptors. Thus, Mim1 plays an important role in the efficient assembly of the mitochondrial TOM complex.

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.

Designing a Better Experience: A Qualitative Investigation of Student Engineering Internships

ERIC Educational Resources Information Center

Paknejad, Mohammad R.

2016-01-01

Science, Technology, Engineering and Mathematics (STEM) education play a very important role in preparing students with skills necessary to obtain better jobs, solve real-world challenges, and compete in the global economy. STEM education develops critical thinking and the ability to solve complex problems. Research showed that 8 out of 10 most…

Institutional Strategy in a Global Context: The Land-Grant University Experience

ERIC Educational Resources Information Center

Croom, Patricia Wotila

2010-01-01

Internationalization plays an increasingly important role in many universities today. Not only do institutions engage in efforts to inject an international component into the curriculum and to expand study abroad, but also undertake more complex partnerships and forms of cross-border education, in some cases with significant risk. The expanding…

Plays Well with Others: A Study of EFL Learner Reciprocity in Action

ERIC Educational Resources Information Center

Ozkose-Biyik, Cagri; Meskill, Carla

2015-01-01

Classroom observation studies suggest that the teacher-calculus is complex and sensitive to learner behaviors. In language education, this becomes particularly important due to strong emphasis on productive interpersonal interaction. This study set out to understand what constitutes positive learning behaviors in an EFL context. The construct of…

Two Roads Taken: A Literacy Roadmap of an International Scholar

ERIC Educational Resources Information Center

Causarano, Antonio

2017-01-01

Literacy plays such an important role in our lives that being able to know who we are as literate individuals is paramount to live and thrive in a complex literate society in the 21st century. Understanding the relationship between an individual's background (cultural, linguistic, social, political, familial, educational, communal and economic)…

The Importance of Challenging Hegemonic Masculinity in Preventing School Violence

ERIC Educational Resources Information Center

Dragowski, Eliza A.; Scharrón-del Río, María R.

2014-01-01

In this article we argue that efforts to eradicate school violence should include an understanding of the complex social, cultural, and historical contexts in which violence is perpetrated. Specifically, we assert that the production and perpetuation of hegemonic/dominant masculinity plays a pivotal role in various forms of aggression and violence…

Genome size and invasiveness traits in the hybrid meadow knapweed complex (Centaurea x moncktonii) in eastern North America

USDA-ARS?s Scientific Manuscript database

Hybridization and genomic admixture between divergent populations or species may be an important driver of plant invasiveness. Recent studies have emphasized the critical role that reductions in genome size may play in facilitating the rapid evolution of invasiveness, and small genome size has been ...

A Politics of Imperceptibilities, Possibilities and Early Childhood Practice

ERIC Educational Resources Information Center

Cumming, Tamara; Sumsion, Jennifer

2014-01-01

A growing body of research suggests that a range of "hidden" or "less tangible" aspects of early childhood practice play an important part in early childhood practice. The purpose of this article is to contribute to this existing research literature by identifying some of the complex ways that less tangible aspects…

Graded Lexicons: New Resources for Educational Purposes and Much More

ERIC Educational Resources Information Center

Gala, Núria; Billami, Mokhtar B.; François, Thomas; Bernhard, Delphine

2015-01-01

Computational tools and resources play an important role for vocabulary acquisition. Although a large variety of dictionaries and learning games are available, few resources provide information about the complexity of a word, either for learning or for comprehension. The idea here is to use frequency counts combined with intralexical variables to…

Shaping (Reflexive) Professional Identities across an Undergraduate Degree Programme: A Longitudinal Case Study

ERIC Educational Resources Information Center

Ryan, Mary; Carmichael, Mary-Ann

2016-01-01

In our complex and incongruous professional worlds, where there is no blueprint for dealing with unpredictable people and events, it is imperative that individuals develop reflexive approaches to professional identity building. Notwithstanding the importance of disciplinary knowledge and skills, higher education has a crucial role to play in…

Wood and Chemistry – or How to Combine Bob Heath's Two Passions into Entomology Research

USDA-ARS?s Scientific Manuscript database

Plants generally produce complex mixtures of terpenoids that may differ greatly among species. Terpenoids, such C10 monoterpenes and C15 sesquiterpenes, are known to play an important role in the biology and ecology of plants, directly or indirectly influencing their interactions with their biotic e...

Narcissism: The Good, the Bad, and the Ugly

ERIC Educational Resources Information Center

Spencer, Vicky G.; Garcia-Simpson, Cynthia; Newland, Shera

2007-01-01

The purpose of this article was to explore the complex issues surrounding the behaviors exhibited by students who have Narcissistic Personality Disorder (NPD) and the role the disorder may play in school violence. Students with NPD are often characterized by arrogance, grandiosity, and self-importance; a preoccupation with fantasies of success and…

Black-White Summer Learning Gaps: Interpreting the Variability of Estimates across Representations

ERIC Educational Resources Information Center

Quinn, David M.

2015-01-01

The estimation of racial test score gap trends plays an important role in monitoring educational equality. Documenting gap trends is complex, however, and estimates can differ depending on the metric, modeling strategy, and psychometric assumptions. The sensitivity of summer learning gap estimates to these factors has been under-examined. Using…

Higher Education and Health Care at a Crossroads

ERIC Educational Resources Information Center

Kirch, Darrell G.

2011-01-01

As major providers and consumers of health care, higher-education institutions have an important role to play in improving health and the nation's health-care system. Health care is a complex issue for colleges and universities. Not only do institutions of higher education provide health insurance to faculty members, staff members, and students,…

Complex modeling of technological processes in pneumatic mixers for production of dry construction mixtures

NASA Astrophysics Data System (ADS)

Orekhova, T. N.; Nosov, O. A.; Prokopenko, V. S.; Kachaev, A. E.

2018-03-01

The improvement of the design of the pneumatic mixers aimed at the possibility of obtaining homogeneous disperse systems, while the resource and energy saving issues play an important role in the conditions of enterprises that use this type of equipment in their technological chain, is described in the article.

Telephone Coaching in Dialectical Behavior Therapy: A Decision-Tree Model for Managing Inter-Session Contact with Clients

ERIC Educational Resources Information Center

Ben-Porath, Denise D.; Koons, Cedar R.

2005-01-01

Several studies have indicated that telephone coaching can play an important role in psychological intervention (Beebe, 2001; Burgess & Chalder, 2001; Meyersberg, 1985). Less well understood, however, is the role of telephone coaching with severe, complex, multiproblem clients, such as those diagnosed with borderline personality disorder.…

Enhancing Architecture-Implementation Conformance with Change Management and Support for Behavioral Mapping

ERIC Educational Resources Information Center

Zheng, Yongjie

2012-01-01

Software architecture plays an increasingly important role in complex software development. Its further application, however, is challenged by the fact that software architecture, over time, is often found not conformant to its implementation. This is usually caused by frequent development changes made to both artifacts. Against this background,…

Insights from Cognitive Neuroscience: The Importance of Executive Function for Early Reading Development and Education

ERIC Educational Resources Information Center

Cartwright, Kelly B.

2012-01-01

Research Findings: Executive function begins to develop in infancy and involves an array of processes, such as attention, inhibition, working memory, and cognitive flexibility, which provide the means by which individuals control their own behavior, work toward goals, and manage complex cognitive processes. Thus, executive function plays a…

Using Home Irrigation Users' Perceptions to Inform Water Conservation Programs

ERIC Educational Resources Information Center

Warner, Laura A.; Chaudhary, Anil Kumar; Lamm, Alexa J.; Rumble, Joy N.; Momol, Esen

2017-01-01

Targeted agricultural education programs can play a role in solving complex water issues. This article applies importance-performance analysis to examine dimensions of water resources that may inform local water conservation campaigns in the United States. The purpose of this study was to generate a deep understanding of home irrigation users'…

The Creative Soccer Platform: New Strategies for Stimulating Creativity in Organized Youth Soccer Practice

ERIC Educational Resources Information Center

Rasmussen, Ludvig Johan Torp; Østergaard, Lars Domino

2016-01-01

Creativity is essential in soccer due to the unpredictable and complex situations occurring in the game, where stereotypical play gradually loses its efficiency. Further, creativity is an important psychological factor for the development of soccer expertise, and valuing creativity increases satisfaction and well-being. Although creative players…

Organization Development: An Approach for Achieving Desired Organizational Goals within the Venezuelan Navy.

DTIC Science & Technology

1982-06-01

Machismo , the complex of beliefs and attitudes that came to define masculinity, stressed chivalry, virility, courage and daring, played an important...continuum. In between lies a currently stagnant middle class. Sex Role Differentiation: " Machismo " is still a strong tendency and so is the "Marianismo

The Search Is on: Engendering Faculty Diversity through More Effective Search and Recruitment

ERIC Educational Resources Information Center

Bilimoria, Diana; Buch, Kimberly K.

2010-01-01

The underrepresentation of women and minority faculty in the science, technology, engineering, and mathematics (STEM) disciplines continues to be a major concern to university leaders, policy makers, and scientists. While a number of complex factors across the entire academic pipeline play significant roles in this problem, important contributing…

The canine and feline skin microbiome in health and disease.

PubMed

Weese, J Scott

2013-02-01

The skin harbours a diverse and abundant, yet inadequately investigated, microbial population. The population is believed to play an important role in both the pathophysiology and the prevention of disease, through a variety of poorly explored mechanisms. Early studies of the skin microbiota in dogs and cats reported a minimally diverse microbial composition of low overall abundance, most probably as a reflection of the limitations of testing methodology. Despite these limitations, it was clear that the bacterial population of the skin plays an important role in disease and in changes in response to both infectious and noninfectious diseases. Recent advances in technology are challenging some previous assumptions about the canine and feline skin microbiota and, with preliminary application of next-generation sequenced-based methods, it is apparent that the diversity and complexity of the canine skin microbiome has been greatly underestimated. A better understanding of this complex microbial population is critical for elucidation of the pathophysiology of various dermatological (and perhaps systemic) diseases and to develop novel ways to manipulate this microbial population to prevent or treat disease. © 2013 The Author. Veterinary Dermatology © 2013 ESVD and ACVD.

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

Carvalho, R. S.; Ávila, H. C.; Cremona, M., E-mail: cremona@fis.puc-rio.br

The recently discovered organic magnetoresistance effect (OMAR) reveals the spin-dependent behavior of the charge transport in organic semiconductors. So far, it is known that hyperfine interactions play an important role in this phenomenon and also that spin-orbit coupling is negligible for light-atom based compounds. However, in the presence of heavy atoms, spin-orbit interactions should play an important role in OMAR. It is known that these interactions are responsible for singlet and triplet states mixing via intersystem crossing and the change of spin-charge relaxation time in the charge mobility process. In this work, we report a dramatic change in the OMARmore » effect caused by the presence of strong intramolecular spin-orbit coupling in a series of rare-earth quinolate organic complex-based devices. Our data show a different OMAR lineshape compared with the OMAR lineshape of tris(8-hydroxyquinolinate) aluminum-based devices, which are well described in the literature. In addition, electronic structure calculations based on density functional theory help to establish the connection between this results and the presence of heavy central ions in the different complexes.« less

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

Marcianò, G.; Huang, D. T., E-mail: d.huang@beatson.gla.ac.uk

The Spt16–SSRP1 heterodimer is a histone chaperone that plays an important role in regulating chromatin assembly. Here, a crystal structure of the N-terminal domain of human Spt16 is presented and it is shown that this domain may contribute to histone binding. The histone chaperone FACT plays an important role in facilitating nucleosome assembly and disassembly during transcription. FACT is a heterodimeric complex consisting of Spt16 and SSRP1. The N-terminal domain of Spt16 resembles an inactive aminopeptidase. How this domain contributes to the histone chaperone activity of FACT remains elusive. Here, the crystal structure of the N-terminal domain (NTD) of humanmore » Spt16 is reported at a resolution of 1.84 Å. The structure adopts an aminopeptidase-like fold similar to those of the Saccharomyces cerevisiae and Schizosaccharomyces pombe Spt16 NTDs. Isothermal titration calorimetry analyses show that human Spt16 NTD binds histones H3/H4 with low-micromolar affinity, suggesting that Spt16 NTD may contribute to histone binding in the FACT complex. Surface-residue conservation and electrostatic analysis reveal a conserved acidic patch that may be involved in histone binding.« less

Senescence and the pro-tumorigenic stroma.

PubMed

Alspach, Elise; Fu, Yujie; Stewart, Sheila A

2013-01-01

Hayflick and Moorhead first described senescence in the late 1960's as a permanent growth arrest that primary cells underwent after a defined number of cellular divisions in culture. This observation gave rise to the hypothesis that cells contained an internal counting mechanism that limited cellular division and that this limit was an important barrier to cellular transformation. What began as an in vitro observation has led to an immense body of work that reaches into all fields of biology and is of particular interest in the areas of aging, tissue regeneration, and tumorigenesis. The initially simplistic view that senescence limits cellular division and contributes to aging while stymying tumorigenesis has now evolved into an important and complex biological process that has numerous caveats and often opposing effects on tumorigenesis. In this review, we limit our discussion to the complex role senescence plays in tumorigenesis. Throughout the review we attempt to draw many parallels to other systems including the role senescent cells play in the tumor microenvironment and their significant molecular and phenotypic similarities to cancer associated fibroblasts (CAFs).

Ontogenetic Trajectories of Chimpanzee Social Play: Similarities with Humans

PubMed Central

Cordoni, Giada; Palagi, Elisabetta

2011-01-01

Social play, a widespread phenomenon in mammals, is a multifunctional behavior, which can have many different roles according to species, sex, age, relationship quality between playmates, group membership, context, and habitat. Play joins and cuts across a variety of disciplines leading directly to inquiries relating to individual developmental changes and species adaptation, thus the importance of comparative studies appears evident. Here, we aim at proposing a possible ontogenetic pathway of chimpanzee play (Pan troglodytes) and contrast our data with those of human play. Chimpanzee play shows a number of changes from infancy to juvenility. Particularly, solitary and social play follows different developmental trajectories. While solitary play peaks in infancy, social play does not show any quantitative variation between infancy and juvenility but shows a strong qualitative variation in complexity, asymmetry, and playmate choice. Like laughter in humans, the playful expressions in chimpanzees (at the different age phases) seem to have a role in advertising cooperative dispositions and intentions thus increasing the likelihood of engaging in solid social relationships. In conclusion, in chimpanzees, as in humans, both play behavior and the signals that accompany play serve multiple functions according to the different age phases. PMID:22110630

Ontogenetic trajectories of chimpanzee social play: similarities with humans.

PubMed

Cordoni, Giada; Palagi, Elisabetta

2011-01-01

Social play, a widespread phenomenon in mammals, is a multifunctional behavior, which can have many different roles according to species, sex, age, relationship quality between playmates, group membership, context, and habitat. Play joins and cuts across a variety of disciplines leading directly to inquiries relating to individual developmental changes and species adaptation, thus the importance of comparative studies appears evident. Here, we aim at proposing a possible ontogenetic pathway of chimpanzee play (Pan troglodytes) and contrast our data with those of human play. Chimpanzee play shows a number of changes from infancy to juvenility. Particularly, solitary and social play follows different developmental trajectories. While solitary play peaks in infancy, social play does not show any quantitative variation between infancy and juvenility but shows a strong qualitative variation in complexity, asymmetry, and playmate choice. Like laughter in humans, the playful expressions in chimpanzees (at the different age phases) seem to have a role in advertising cooperative dispositions and intentions thus increasing the likelihood of engaging in solid social relationships. In conclusion, in chimpanzees, as in humans, both play behavior and the signals that accompany play serve multiple functions according to the different age phases.

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.

Chlamydia Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning.

PubMed

Wesolowski, Jordan; Weber, Mary M; Nawrotek, Agata; Dooley, Cheryl A; Calderon, Mike; St Croix, Claudette M; Hackstadt, Ted; Cherfils, Jacqueline; Paumet, Fabienne

2017-05-02

The intracellular bacterium Chlamydia trachomatis develops in a parasitic compartment called the inclusion. Posttranslationally modified microtubules encase the inclusion, controlling the positioning of Golgi complex fragments around the inclusion. The molecular mechanisms by which Chlamydia coopts the host cytoskeleton and the Golgi complex to sustain its infectious compartment are unknown. Here, using a genetically modified Chlamydia strain, we discovered that both posttranslationally modified microtubules and Golgi complex positioning around the inclusion are controlled by the chlamydial inclusion protein CT813/CTL0184/InaC and host ARF GTPases. CT813 recruits ARF1 and ARF4 to the inclusion membrane, where they induce posttranslationally modified microtubules. Similarly, both ARF isoforms are required for the repositioning of Golgi complex fragments around the inclusion. We demonstrate that CT813 directly recruits ARF GTPases on the inclusion membrane and plays a pivotal role in their activation. Together, these results reveal that Chlamydia uses CT813 to hijack ARF GTPases to couple posttranslationally modified microtubules and Golgi complex repositioning at the inclusion. IMPORTANCE Chlamydia trachomatis is an important cause of morbidity and a significant economic burden in the world. However, how Chlamydia develops its intracellular compartment, the so-called inclusion, is poorly understood. Using genetically engineered Chlamydia mutants, we discovered that the effector protein CT813 recruits and activates host ADP-ribosylation factor 1 (ARF1) and ARF4 to regulate microtubules. In this context, CT813 acts as a molecular platform that induces the posttranslational modification of microtubules around the inclusion. These cages are then used to reposition the Golgi complex during infection and promote the development of the inclusion. This study provides the first evidence that ARF1 and ARF4 play critical roles in controlling posttranslationally modified microtubules around the inclusion and that Chlamydia trachomatis hijacks this novel function of ARF to reposition the Golgi complex. Copyright © 2017 Wesolowski et al.

Jab1 Mediates Protein Degradation of Rad9/Rad1/Hus1 Checkpoint Complex

PubMed Central

Huang, Jin; Yuan, Honglin; Lu, Chongyuan; Liu, Ximeng; Cao, Xu; Wan, Mei

2009-01-01

Summary The Rad1-Rad9-Hus1 (9-1-1) complex serves a dual role as a DNA-damage sensor in checkpoint signaling and as a mediator in DNA repair pathway. However, the intercellular mechanisms that regulate 9-1-1 complex are poorly understood. Jab1, the fifth component of the COP9 signalosome complex, plays a central role in the degradation of multiple proteins and is emerging as an important regulator in cancer development. Here, we tested the hypothesis that Jab1 controls the protein stability of the 9-1-1 complex via the proteosome pathway. We provide evidence that Jab1 physically associates with the 9-1-1 complex. This association is mediated through direct interaction between Jab1 and Rad1, one of the subunits of 9-1-1 complex. Importantly, Jab1 causes the translocation of the 9-1-1 complex from the nucleus to the cytoplasm, mediating rapid degradation of the 9-1-1 complex via 26S proteasome. Furthermore, Jab1 significantly suppresses checkpoint signaling activation, DNA synthesis recovery from blockage and cell viability after replication stresses such as UV exposure, γ radiation and hydroxyurea treatment. These results suggest that Jab1 is an important regulator for 9-1-1 protein stability control in cells, which may provide novel information on the involvement of Jab1 in checkpoint and DNA repair signaling in response to DNA damage. PMID:17583730

Path induced coherent energy transfer in light-harvesting complexes in purple bacteria

NASA Astrophysics Data System (ADS)

Sun, Kewei; Ye, Jun; Zhao, Yang

2014-09-01

Features of path dependent energy transfer in a dual-ring light-harvesting (LH2) complexes (B850) system have been examined in detail systematically. The Frenkel-Dirac time dependent variational method with the Davydov D1 Ansatz is employed with detailed evolution of polaron dynamics in real space readily obtained. It is found that the phase of the transmission amplitude through the LH2 complexes plays an important role in constructing the coherent excitonic energy transfer. It is also found that the symmetry breaking caused by the dimerization of bacteriochlorophylls and coherence or correlation between two rings will be conducive in enhancing the exciton transfer efficiency.

Small-time Scale Network Traffic Prediction Based on Complex-valued Neural Network

NASA Astrophysics Data System (ADS)

Yang, Bin

2017-07-01

Accurate models play an important role in capturing the significant characteristics of the network traffic, analyzing the network dynamic, and improving the forecasting accuracy for system dynamics. In this study, complex-valued neural network (CVNN) model is proposed to further improve the accuracy of small-time scale network traffic forecasting. Artificial bee colony (ABC) algorithm is proposed to optimize the complex-valued and real-valued parameters of CVNN model. Small-scale traffic measurements data namely the TCP traffic data is used to test the performance of CVNN model. Experimental results reveal that CVNN model forecasts the small-time scale network traffic measurement data very accurately

Hsp90 can Accommodate the Simultaneous Binding of the FKBP52 and HOP Proteins

PubMed Central

Hildenbrand, Zacariah L.; Molugu, Sudheer K.; Herrera, Nadia; Ramirez, Citlally; Xiao, Chuan; Bernal, Ricardo A.

2011-01-01

The regulation of steroidogenic hormone receptor-mediated activity plays an important role in the development of hormone-dependent cancers. For example, during prostate carcinogenesis, the regulatory function played by the androgen receptor is often converted from a growth suppressor to an oncogene thus promoting prostate cancer cell survival and eventual metastasis. Within the cytoplasm, steroid hormone receptor activity is regulated by the Hsp90 chaperone in conjunction with a series of co-chaperone proteins. Collectively, Hsp90 and its binding associates form a large heteromeric complex that scaffold the fully mature receptor for binding with the respective hormone. To date our understanding of the interactions between Hsp90 with the various TPR domain-containing co-chaperone proteins is limited due to a lack of available structural information. Here we present the stable formation of Hsp902-FKBP521- HOP2 and Hsp902-FKBP521-p232-HOP2 complexes as detected by immunoprecipitation, time course dynamic light scattering and electron microscopy. The simultaneous binding of FKBP52 and HOP to the Hsp90 dimer provide direct evidence of a novel chaperone sub-complex that likely plays a transient role in the regulation of the fully mature steroid hormone receptor. PMID:21378414

Differential Effects of Low-Molecular-Weight Organic Acids on the Mobilization of Soil-Borne Arsenic and Trace Metals.

PubMed

Nworie, Obinna Elijah; Qin, Junhao; Lin, Chuxia

2017-08-21

A batch experiment was conducted to examine the effects of six low-molecular-weight organic acids on the mobilization of arsenic and trace metals from a range of contaminated soils. The results showed that the organic acids behaved differently when reacting with soil-borne As and trace metals. Oxalic acid and acetic acid had the strongest and weakest capacity to mobilize the investigated elements, respectively. The solubilisation of iron oxides by the organic acids appears to play a critical role in mobilizing other trace metals and As. Apart from acidification and complexation, reductive dissolution played a dominant role in the dissolution of iron oxides in the presence of oxalic acid, while acidification tended to be more important for dissolving iron oxides in the presence of other organic acids. The unique capacity of oxalic acid to solubilize iron oxides tended to affect the mobilization of other elements in different ways. For Cu, Mn, and Zn, acidification-driven mobilization was likely to be dominant while complexation might play a major role in Pb mobilization. The formation of soluble Fe and Pb oxalate complexes could effectively prevent arsenate or arsenite from combining with these metals to form solid phases of Fe or Pb arsenate or arsenite.

Identification of a small TAF complex and its role in the assembly of TAF-containing complexes.

PubMed

Demény, Màté A; Soutoglou, Evi; Nagy, Zita; Scheer, Elisabeth; Jànoshàzi, Agnes; Richardot, Magalie; Argentini, Manuela; Kessler, Pascal; Tora, Laszlo

2007-03-21

TFIID plays a role in nucleating RNA polymerase II preinitiation complex assembly on protein-coding genes. TFIID is a multisubunit complex comprised of the TATA box binding protein (TBP) and 14 TBP-associated factors (TAFs). Another class of multiprotein transcriptional regulatory complexes having histone acetyl transferase (HAT) activity, and containing TAFs, includes TFTC, STAGA and the PCAF/GCN5 complex. Looking for as yet undiscovered subunits by a proteomic approach, we had identified TAF8 and SPT7L in human TFTC preparations. Subsequently, however, we demonstrated that TAF8 was not a stable component of TFTC, but that it is present in a small TAF complex (SMAT), containing TAF8, TAF10 and SPT7L, that co-purified with TFTC. Thus, TAF8 is a subunit of both TFIID and SMAT. The latter has to be involved in a pathway of complex formation distinct from the other known TAF complexes, since these three histone fold (HF)-containing proteins (TAF8, TAF10 and SPT7L) can never be found together either in TFIID or in STAGA/TFTC HAT complexes. Here we show that TAF8 is absolutely necessary for the integration of TAF10 in a higher order TFIID core complex containing seven TAFs. TAF8 forms a heterodimer with TAF10 through its HF and proline rich domains, and also interacts with SPT7L through its C-terminal region, and the three proteins form a complex in vitro and in vivo. Thus, the TAF8-TAF10 and TAF10-SPT7L HF pairs, and also the SMAT complex, seem to be important regulators of the composition of different TFIID and/or STAGA/TFTC complexes in the nucleus and consequently may play a role in gene regulation.

Regulation of metabolism by the Mediator complex.

PubMed

Youn, Dou Yeon; Xiaoli, Alus M; Pessin, Jeffrey E; Yang, Fajun

2016-01-01

The Mediator complex was originally discovered in yeast, but it is conserved in all eukaryotes. Its best-known function is to regulate RNA polymerase II-dependent gene transcription. Although the mechanisms by which the Mediator complex regulates transcription are often complicated by the context-dependent regulation, this transcription cofactor complex plays a pivotal role in numerous biological pathways. Biochemical, molecular, and physiological studies using cancer cell lines or model organisms have established the current paradigm of the Mediator functions. However, the physiological roles of the mammalian Mediator complex remain poorly defined, but have attracted a great interest in recent years. In this short review, we will summarize some of the reported functions of selective Mediator subunits in the regulation of metabolism. These intriguing findings suggest that the Mediator complex may be an important player in nutrient sensing and energy balance in mammals.

Complexity in the new NHS: longitudinal case studies of CCGs in England

PubMed Central

Checkland, Katherine; Coleman, Anna; Perkins, Neil

2016-01-01

Objective The reform in the English National Health Services (NHS) under the Health and Social Care Act 2012 is unlike previous NHS reorganisations. The establishment of clinical commissioning groups (CCGs) was intended to be ‘bottom up’ with no central blueprint. This paper sets out to offer evidence about how this process has played out in practice and examines the implications of the complexity and variation which emerged. Design Detailed case studies in CCGs across England, using interviews, observation and documentary analysis. Using realist framework, we unpacked the complexity of CCG structures. Setting/participants In phase 1 of the study (January 2011 to September 2012), we conducted 96 interviews, 439 h of observation in a wide variety of meetings, 2 online surveys and 38 follow-up telephone interviews. In phase 2 (April 2013 to March 2015), we conducted 42 interviews with general practitioners (GPs) and managers and observation of 48 different types of meetings. Results Our study has highlighted the complexity inherent in CCGs, arising out of the relatively permissive environment in which they developed. Not only are they very different from one another in size, but also in structure, functions between different bodies and the roles played by GPs. Conclusions The complexity and lack of uniformity of CCGs is important as it makes it difficult for those who must engage with CCGs to know who to approach at what level. This is of increasing importance as CCGs are moving towards greater integration across health and social care. Our study also suggests that there is little consensus as to what being a ‘membership’ organisation means and how it should operate. The lack of uniformity in CCG structure and lack of clarity over the meaning of ‘membership’ raises questions over accountability, which becomes of greater importance as CCG is taking over responsibility for primary care co-commissioning. PMID:26743708

Complexity in the new NHS: longitudinal case studies of CCGs in England.

PubMed

Checkland, Katherine; McDermott, Imelda; Coleman, Anna; Perkins, Neil

2016-01-07

The reform in the English National Health Services (NHS) under the Health and Social Care Act 2012 is unlike previous NHS reorganisations. The establishment of clinical commissioning groups (CCGs) was intended to be 'bottom up' with no central blueprint. This paper sets out to offer evidence about how this process has played out in practice and examines the implications of the complexity and variation which emerged. Detailed case studies in CCGs across England, using interviews, observation and documentary analysis. Using realist framework, we unpacked the complexity of CCG structures. In phase 1 of the study (January 2011 to September 2012), we conducted 96 interviews, 439 h of observation in a wide variety of meetings, 2 online surveys and 38 follow-up telephone interviews. In phase 2 (April 2013 to March 2015), we conducted 42 interviews with general practitioners (GPs) and managers and observation of 48 different types of meetings. Our study has highlighted the complexity inherent in CCGs, arising out of the relatively permissive environment in which they developed. Not only are they very different from one another in size, but also in structure, functions between different bodies and the roles played by GPs. The complexity and lack of uniformity of CCGs is important as it makes it difficult for those who must engage with CCGs to know who to approach at what level. This is of increasing importance as CCGs are moving towards greater integration across health and social care. Our study also suggests that there is little consensus as to what being a 'membership' organisation means and how it should operate. The lack of uniformity in CCG structure and lack of clarity over the meaning of 'membership' raises questions over accountability, which becomes of greater importance as CCG is taking over responsibility for primary care co-commissioning. 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/

Identification of a Golgi apparatus protein complex important for the asexual erythrocytic cycle of the malaria parasite Plasmodium falciparum.

PubMed

Hallée, Stéphanie; Thériault, Catherine; Gagnon, Dominic; Kehrer, Jessica; Frischknecht, Friedrich; Mair, Gunnar R; Richard, Dave

2018-03-26

Compared with other eukaryotic cell types, malaria parasites appear to possess a more rudimentary Golgi apparatus being composed of dispersed, unstacked cis and trans-cisternae. Despite playing a central role in the secretory pathway of the parasite, few Plasmodium Golgi resident proteins have been characterised. We had previously identified a new Golgi resident protein of unknown function, which we had named Golgi Protein 1, and now show that it forms a complex with a previously uncharacterised transmembrane protein (Golgi Protein 2, GP2). The Golgi Protein complex localises to the cis-Golgi throughout the erythrocytic cycle and potentially also during the mosquito stages. Analysis of parasite strains where GP1 expression is conditionally repressed and/or the GP2 gene is inactivated reveals that though the Golgi protein complex is not essential at any stage of the parasite life cycle, it is important for optimal asexual development in the blood stages. © 2018 John Wiley & Sons Ltd.

Molecular dynamics study of thermodynamic stability and dynamics of [Li(glyme)]+ complex in lithium-glyme solvate ionic liquids

NASA Astrophysics Data System (ADS)

Shinoda, Wataru; Hatanaka, Yuta; Hirakawa, Masashi; Okazaki, Susumu; Tsuzuki, Seiji; Ueno, Kazuhide; Watanabe, Masayoshi

2018-05-01

Equimolar mixtures of glymes and organic lithium salts are known to produce solvate ionic liquids, in which the stability of the [Li(glyme)]+ complex plays an important role in determining the ionic dynamics. Since these mixtures have attractive physicochemical properties for application as electrolytes, it is important to understand the dependence of the stability of the [Li(glyme)]+ complex on the ion dynamics. A series of microsecond molecular dynamics simulations has been conducted to investigate the dynamic properties of these solvate ionic liquids. Successful solvate ionic liquids with high stability of the [Li(glyme)]+ complex have been shown to have enhanced ion dynamics. Li-glyme pair exchange rarely occurs: its characteristic time is longer than that of ion diffusion by one or two orders of magnitude. Li-glyme pair exchange most likely occurs through cluster formation involving multiple [Li(glyme)]+ pairs. In this process, multiple exchanges likely take place in a concerted manner without the production of energetically unfavorable free glyme or free Li+ ions.

miR-181c-BRK1 axis plays a key role in actin cytoskeleton-dependent T cell function.

PubMed

Lim, Shok Ping; Ioannou, Nikolaos; Ramsay, Alan G; Darling, David; Gäken, Joop; Mufti, Ghulam J

2018-05-01

MicroRNAs are short endogenous noncoding RNAs that play pivotal roles in a diverse range of cellular processes. The miR-181 family is important in T cell development, proliferation, and activation. In this study, we have identified BRK1 as a potential target of miR-181c using a dual selection functional assay and have showed that miR-181c regulates BRK1 by translational inhibition. Given the importance of miR-181 in T cell function and the potential role of BRK1 in the involvement of WAVE2 complex and actin polymerization in T cells, we therefore investigated the influence of miR-181c-BRK1 axis in T cell function. Stimulation of PBMC derived CD3 + T cells resulted in reduced miR-181c expression and up-regulation of BRK1 protein expression, suggesting that miR-181c-BRK1 axis is important in T cell activation. We further showed that overexpression of miR-181c or suppression of BRK1 resulted in inhibition of T cell activation and actin polymerization coupled with defective lamellipodia generation and immunological synapse formation. Additionally, we found that BRK1 silencing led to reduced expressions of other proteins in the WAVE2 complex, suggesting that the impairment of T cell actin dynamics was a result of the instability of the WAVE2 complex following BRK1 depletion. Collectively, we demonstrated that miR-181c reduces BRK1 protein expression level and highlighted the important role of miR-181c-BRK1 axis in T cell activation and actin polymerization-mediated T cell functions. ©2018 Society for Leukocyte Biology.

A core hSSB1–INTS complex participates in the DNA damage response

PubMed Central

Zhang, Feng; Ma, Teng; Yu, Xiaochun

2013-01-01

Summary Human single-stranded DNA-binding protein 1 (hSSB1) plays an important role in the DNA damage response and the maintenance of genomic stability. It has been shown that the core hSSB1 complex contains hSSB1, INTS3 and C9orf80. Using protein affinity purification, we have identified integrator complex subunit 6 (INTS6) as a major subunit of the core hSSB1 complex. INTS6 forms a stable complex with INTS3 and hSSB1 both in vitro and in vivo. In this complex, INTS6 directly interacts with INTS3. In response to the DNA damage response, along with INTS3 and hSSB1, INTS6 relocates to the DNA damage sites. Moreover, the hSSB1–INTS complex regulates the accumulation of RAD51 and BRCA1 at DNA damage sites and the correlated homologous recombination. PMID:23986477

The MeCP1 complex represses transcription through preferential binding, remodeling, and deacetylating methylated nucleosomes

PubMed Central

Feng, Qin; Zhang, Yi

2001-01-01

Histone deacetylation plays an important role in methylated DNA silencing. Recent studies indicated that the methyl-CpG-binding protein, MBD2, is a component of the MeCP1 histone deacetylase complex. Interestingly, MBD2 is able to recruit the nucleosome remodeling and histone deacetylase, NuRD, to methylated DNA in vitro. To understand the relationship between the MeCP1 complex and the NuRD complex, we purified the MeCP1 complex to homogeneity and found that it contains 10 major polypeptides including MBD2 and all of the known NuRD components. Functional analysis of the purified MeCP1 complex revealed that it preferentially binds, remodels, and deacetylates methylated nucleosomes. Thus, our study defines the MeCP1 complex, and provides biochemical evidence linking nucleosome remodeling and histone deacetylation to methylated gene silencing. PMID:11297506

Interhemispheric Control of Unilateral Movement

PubMed Central

Beaulé, Vincent; Tremblay, Sara; Théoret, Hugo

2012-01-01

To perform strictly unilateral movements, the brain relies on a large cortical and subcortical network. This network enables healthy adults to perform complex unimanual motor tasks without the activation of contralateral muscles. However, mirror movements (involuntary movements in ipsilateral muscles that can accompany intended movement) can be seen in healthy individuals if a task is complex or fatiguing, in childhood, and with increasing age. Lateralization of movement depends on complex interhemispheric communication between cortical (i.e., dorsal premotor cortex, supplementary motor area) and subcortical (i.e., basal ganglia) areas, probably coursing through the corpus callosum (CC). Here, we will focus on transcallosal interhemispheric inhibition (IHI), which facilitates complex unilateral movements and appears to play an important role in handedness, pathological conditions such as Parkinson's disease, and stroke recovery. PMID:23304559

Examining the locus of age effects on complex span tasks.

PubMed

McCabe, Jennifer; Hartman, Marilyn

2003-09-01

To investigate the locus of age effects on complex span tasks, the authors evaluated the contributions of working memory functions and processing speed. Age differences were found in measures of storage capacity, language processing speed, and lower level speed. Statistically controlling for each of these in hierarchical regressions substantially reduced, but did not eliminate, the complex span age effect. Accounting for lower level speed and storage, however, removed essentially the entire age effect, suggesting that both functions play important and independent roles. Additional evidence for the role of storage capacity was the absence of complex span age differences with span size calibrated to individual word span performance. Explanations for age differences based on inhibition and concurrent task performamce were not supported.

Assembly and activation of neurotrophic factor receptor complexes.

PubMed

Simi, Anastasia; Ibáñez, Carlos F

2010-04-01

Neurotrophic factors play important roles in the development and function of both neuronal and glial elements of the central and peripheral nervous systems. Their functional diversity is in part based on their ability to interact with alternative complexes of receptor molecules. This review focuses on our current understanding of the mechanisms that govern the assembly and activation of neurotrophic factor receptor complexes. The realization that many, if not the majority, of these complexes exist in a preassembled form at the plasma membrane has forced the revision of classical ligand-mediated oligomerization models, and led to the discovery of novel mechanisms of receptor activation and generation of signaling diversity which are likely to be shared by many different classes of receptors.

Young Children's Playfully Complex Communication: Distributed Imagination

ERIC Educational Resources Information Center

Alcock, Sophie

2010-01-01

This paper draws on research exploring young children's playful and humorous communication. It explores how playful activity mediates and connects children in complex activity systems where imagination, cognition, and consciousness become distributed across individuals. Children's playfulness is mediated and distributed via artefacts (tools, signs…

A theoretical study of complexes formed between cations and curved aromatic systems: electrostatics does not always control cation-π interaction.

PubMed

Carrazana-García, Jorge A; Cabaleiro-Lago, Enrique M; Rodríguez-Otero, Jesús

2017-04-19

The present work studies the interaction of two extended curved π-systems (corannulene and sumanene) with various cations (sodium, potassium, ammonium, tetramethylammonium, guanidinium and imidazolium). Polyatomic cations are models of groups found in important biomolecules in which cation-π interaction plays a fundamental role. The results indicate an important size effect: with extended π systems and cations of the size of potassium and larger, dispersion is much more important than has been generally recognized for cation-π interactions. In most of the systems studied here, the stability of the cation-π complexes is the result of a balanced combination of electrostatic, induction and dispersion contributions. None of the systems studied here owes its stability to the electrostatic interaction more than 42%. Induction dominates stabilization in complexes with sodium, and in some of the potassium and ammonium complexes. In complexes with large cations and with flat cations dispersion is the major stabilizing contribution and can provide more than 50% of the stabilization energy. This implies that theoretical studies of the cation-π interaction involving large or even medium-size fragments require a level of calculation capable of properly modelling dispersion. The separation between the cation and the π system is another important factor to take into account, especially when the fragments of the cation-π complex are bound (for example, to a protein backbone) and cannot interact at the most favourable distance.

Diapause in ticks of the medically important Ixodes ricinus species complex

PubMed Central

Gray, Jeremy S.; Kahl, Olaf; Lane, Robert S.; Levin, Michael L.; Tsao, Jean I.

2017-01-01

Four members of the Ixodes ricinus species complex, Ixodes pacificus, Ixodes persulcatus, Ixodes ricinus and Ixodes scapularis, have, between them, a worldwide distribution within the northern hemisphere. They are responsible for the transmission of several animal and human pathogens, including the causal agents of Lyme borreliosis, tick-borne encephalitis, human granulocytic anaplasmosis and human babesiosis. Despite the importance of these ticks as vectors, the knowledge and understanding of the role that diapause plays in their complex life cycles are confused and incomplete. In view of the continuing geographic spread of these tick species, as well as the effects of climate change on vector-borne diseases, it is timely encourage research on diapause phenomena to improve understanding of their biology and of pathogen transmission dynamics. In our review we seek to clarify thinking on the topic and to address gaps in our knowledge that require the attention of researchers. PMID:27263092

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

The Caenorhabditis elegans LET-418/Mi2 plays a conserved role in lifespan regulation.

PubMed

De Vaux, Véronique; Pfefferli, Catherine; Passannante, Myriam; Belhaj, Khaoula; von Essen, Alina; Sprecher, Simon G; Müller, Fritz; Wicky, Chantal

2013-12-01

The evolutionarily conserved nucleosome-remodeling protein Mi2 is involved in transcriptional repression during development in various model systems, plays a role in embryonic patterning and germ line development, and participates in DNA repair and cell cycle progression. It is the catalytic subunit of the nucleosome remodeling and histone deacetylase (NuRD) complex, a key determinant of differentiation in mammalian embryonic stem cells. In addition, the Drosophila and C. elegans Mi2 homologs participate in another complex, the MEC complex, which also plays an important developmental role in these organisms. Here we show a new and unexpected feature of the C. elegans Mi2 homolog, LET-418/Mi2. Lack of LET-418/Mi2 results in longevity and enhanced stress resistance, a feature that we found to be conserved in Drosophila and in Arabidopsis. The fact that depletion of other components of the NuRD and the MEC complexes did not result in longevity suggests that LET-418 may regulate lifespan in a different molecular context. Genetic interaction studies suggest that let-418 could act in the germ-cell-loss pathway, downstream of kri-1 and tcer-1. On the basis of our data and on previous findings showing a role for let-418 during development, we propose that LET-418/Mi2 could be part of a system that drives development and reproduction with concomitant life-reducing effects later in life. © 2013 the Anatomical Society and John Wiley & Sons Ltd.

Complex thermoelectric materials.

PubMed

Snyder, G Jeffrey; Toberer, Eric S

2008-02-01

Thermoelectric materials, which can generate electricity from waste heat or be used as solid-state Peltier coolers, could play an important role in a global sustainable energy solution. Such a development is contingent on identifying materials with higher thermoelectric efficiency than available at present, which is a challenge owing to the conflicting combination of material traits that are required. Nevertheless, because of modern synthesis and characterization techniques, particularly for nanoscale materials, a new era of complex thermoelectric materials is approaching. We review recent advances in the field, highlighting the strategies used to improve the thermopower and reduce the thermal conductivity.

Formation mechanism of complex pattern on fishes' skin

NASA Astrophysics Data System (ADS)

Li, Xia; Liu, Shuhua

2009-10-01

In this paper, the formation mechanism of the complex patterns observed on the skin of fishes has been investigated by a two-coupled reaction diffusion model. The effects of coupling strength between two layers play an important role in the pattern-forming process. It is found that only the epidermis layer can produce complicated patterns that have structures on more than one length scale. These complicated patterns including super-stripe pattern, mixture of spots and stripe, and white-eye pattern are similar to the pigmentation patterns on fishes' skin.

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.

A Multifaceted Mathematical Approach for Complex Systems

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

Alexander, F.; Anitescu, M.; Bell, J.

2012-03-07

Applied mathematics has an important role to play in developing the tools needed for the analysis, simulation, and optimization of complex problems. These efforts require the development of the mathematical foundations for scientific discovery, engineering design, and risk analysis based on a sound integrated approach for the understanding of complex systems. However, maximizing the impact of applied mathematics on these challenges requires a novel perspective on approaching the mathematical enterprise. Previous reports that have surveyed the DOE's research needs in applied mathematics have played a key role in defining research directions with the community. Although these reports have had significantmore » impact, accurately assessing current research needs requires an evaluation of today's challenges against the backdrop of recent advances in applied mathematics and computing. To address these needs, the DOE Applied Mathematics Program sponsored a Workshop for Mathematics for the Analysis, Simulation and Optimization of Complex Systems on September 13-14, 2011. The workshop had approximately 50 participants from both the national labs and academia. The goal of the workshop was to identify new research areas in applied mathematics that will complement and enhance the existing DOE ASCR Applied Mathematics Program efforts that are needed to address problems associated with complex systems. This report describes recommendations from the workshop and subsequent analysis of the workshop findings by the organizing committee.« less

Educating for a Changing World: The Importance of an Equity Mindset

ERIC Educational Resources Information Center

Ramaley, Judith A.

2014-01-01

Our nation's colleges and universities are being asked to play demanding roles in creating the capacity for active and engaged collaboration and collective action to address complex challenges that are shaping the world we live in. An essential ingredient of any effort to build healthy communities for any purpose, including education, is the…

The Role of Children's Literature in One Rural Town's Elementary School: A Case Study.

ERIC Educational Resources Information Center

Altieri, Jennifer L.

1997-01-01

Surveys all 11 teachers in one rural setting to determine complexities surrounding literature use in that school. Finds the basal played a predominant role in classrooms--only the Chapter I teacher used literature during reading. Finds that "textbooks" were important for teachers and that trade books did not figure much in instruction.…

Social Environmental Risk and Protection: A Typology with Implications for Practice in Elementary Schools

ERIC Educational Resources Information Center

Bowen, Natasha K.; Lee, Jung-Sook; Weller, Bridget E.

2007-01-01

Social environmental assessments can play a critical role in prevention planning in schools. The purpose of this study was to describe the importance of conducting social environmental assessments, demonstrate that complex social environmental data can be simplified into a useful and valid typology, and illustrate how the typology can guide…

Creating My Own Story: Catholic Women's College Students Narrating Their Lives

ERIC Educational Resources Information Center

Enke, Kathryn A. E.; Winters, Kelly T.; Ropers-Huilman, Rebecca

2013-01-01

Given the complex and gendered messages college women receive about their future professional and personal lives, a woman's college experiences play an important role in helping her make difficult life choices. In this article, we present a narrative analysis of the envisioned futures of students at two Catholic women's colleges in the Midwestern…

Implementing a Successful Bilingual Educational Program in Japan: Support for Minority Languages and the Present Climate of Bilingual Education

ERIC Educational Resources Information Center

Cumming, Brett

2011-01-01

Although generally acknowledged as complex and multidimensional, bilingual education, when successful, plays an important role in maintaining and developing bilingualism, resulting in numerous benefits to those who undertake it. This essay will discuss the necessary components and principles of what is required to make a successful bilingual…

Trainee Primary Teachers' Beliefs and Practices about Physical Education during Student Teaching

ERIC Educational Resources Information Center

Tsangaridou, Niki

2008-01-01

Background: In exploring the complexity of teaching, scholars have suggested that greater attention needs to be paid to the teachers' thoughts and actions and to how these affect quality teaching. Up to today, very few studies have investigated the relationship between teachers' beliefs and practices even though it has an important role to play in…

The Role of Personality and Team-Based Product Dissection on Fixation Effects

ERIC Educational Resources Information Center

Toh, Christine; Miller, Scarlett; Kremer, Gül E. Okudan

2013-01-01

Design fixation has been found to be complex in its definition and expression, but it plays an important role in design idea generation. Identifying the factors that influence fixation is crucial in understanding how to enhance the design process and reduce the negative effects of fixation. One way to potentially mitigate fixation is through…

Two-Step Adsorption of PtCl 6 2– Complexes at a Charged Langmuir Monolayer: Role of Hydration and Ion Correlations

DOE PAGES

Uysal, Ahmet; Rock, William; Qiao, Baofu; ...

2017-11-03

Anion exchange at positively charged interfaces plays an important role in a variety of physical and chemical processes. However, the molecular-scale details of these processes, especially with heavy and large anionic complexes, are not well-understood. Here, we studied the adsorption of PtCl 6 2– anionic complexes to floating DPTAP monolayers in the presence of excess Cl– as a function of the bulk chlorometalate concentration. This system aims to simulate the industrial conditions for heavy metal separations with solvent extraction. In situ X-ray scattering and fluorescence measurements, which are element and depth sensitive, show that the chlorometalate ions only adsorb inmore » the diffuse layer at lower concentrations, while they adsorb predominantly in the Stern layer at higher concentrations. The response of DPTAP molecules to the adsorbed ions is determined independently by grazing incidence X-ray diffraction and supports this picture. Molecular dynamics simulations further elucidate the nanoscale structure of the interfacial complexes. The results suggest that ion hydration and ion–ion correlations play a key role in the competitive adsorption process.« less

Design and reactivity of Ni-complexes using pentadentate neutral-polypyridyl ligands: Possible mimics of NiSOD.

PubMed

Snider, Victoria G; Farquhar, Erik R; Allen, Mark; Abu-Spetani, Ayah; Mukherjee, Anusree

2017-10-01

Superoxide plays a key role in cell signaling, but can be cytotoxic within cells unless well regulated by enzymes known as superoxide dismutases (SOD). Nickel superoxide dismutase (NiSOD) catalyzes the disproportion of the harmful superoxide radical into hydrogen peroxide and dioxygen. NiSOD has a unique active site structure that plays an important role in tuning the potential of the nickel center to function as an effective catalyst for superoxide dismutation with diffusion controlled rates. The synthesis of structural and functional analogues of NiSOD provides a route to better understand the role of the nickel active site in superoxide dismutation. In this work, the synthesis of a series of nickel complexes supported by nitrogen rich pentadentate ligands is reported. The complexes have been characterized through absorption spectroscopy, mass spectrometry, and elemental analysis. X-ray absorption spectroscopy was employed to establish the oxidation state and the coordination geometry around the metal center. The reactivity of these complexes toward KO 2 was evaluated to elucidate the role of the coordination sphere in controlling superoxide dismutation reactivity. Copyright © 2017 Elsevier Inc. All rights reserved.

Protein translocation channel of mitochondrial inner membrane and matrix-exposed import motor communicate via two-domain coupling protein

PubMed Central

Banerjee, Rupa; Gladkova, Christina; Mapa, Koyeli; Witte, Gregor; Mokranjac, Dejana

2015-01-01

The majority of mitochondrial proteins are targeted to mitochondria by N-terminal presequences and use the TIM23 complex for their translocation across the mitochondrial inner membrane. During import, translocation through the channel in the inner membrane is coupled to the ATP-dependent action of an Hsp70-based import motor at the matrix face. How these two processes are coordinated remained unclear. We show here that the two domain structure of Tim44 plays a central role in this process. The N-terminal domain of Tim44 interacts with the components of the import motor, whereas its C-terminal domain interacts with the translocation channel and is in contact with translocating proteins. Our data suggest that the translocation channel and the import motor of the TIM23 complex communicate through rearrangements of the two domains of Tim44 that are stimulated by translocating proteins. DOI: http://dx.doi.org/10.7554/eLife.11897.001 PMID:26714107

Understanding titanium-catalysed radical-radical reactions: a DFT study unravels the complex kinetics of ketone-nitrile couplings.

PubMed

Streuff, Jan; Himmel, Daniel; Younas, Sara L

2018-04-03

The computational investigation of a titanium-catalysed reductive radical-radical coupling is reported. The results match the conclusions from an earlier experimental study and enable a further interpretation of the previously observed complex reaction kinetics. Furthermore, the interplay between neutral and cationic reaction pathways in titanium(iii)-catalysed reactions is investigated for the first time. The results show that hydrochloride additives and reaction byproducts play an important role in the respective equilibria. A full reaction profile is assembled and the computed activation barrier is found to be in reasonable agreement with the experiment. The conclusions are of fundamental importance to the field of low-valent titanium catalysis and the understanding of related catalytic radical-radical coupling reactions.

Direct DNA binding by Brca1.

PubMed

Paull, T T; Cortez, D; Bowers, B; Elledge, S J; Gellert, M

2001-05-22

The tumor suppressor Brca1 plays an important role in protecting mammalian cells against genomic instability, but little is known about its modes of action. In this work we demonstrate that recombinant human Brca1 protein binds strongly to DNA, an activity conferred by a domain in the center of the Brca1 polypeptide. As a result of this binding, Brca1 inhibits the nucleolytic activities of the Mre11/Rad50/Nbs1 complex, an enzyme implicated in numerous aspects of double-strand break repair. Brca1 displays a preference for branched DNA structures and forms protein-DNA complexes cooperatively between multiple DNA strands, but without DNA sequence specificity. This fundamental property of Brca1 may be an important part of its role in DNA repair and transcription.

[Knowledge transfer in the light of changing values].

PubMed

Hahnenkamp, Klaus; Brinkrolf, Peter; Wenning, Markus; Hasebrook, Joachim

2013-11-01

Besides its formal and legal relevance, postgraduate medical education plays an important role in recruiting and retaining employees. Success of graduate education is affected by a changing environment: the former employer market is turning into an employee market. Demographic changes are taking place and a new generation of employees 'Generation Y' is entering the job market. In addition, working conditions are changing: part-time work is increasing and the learning behavior of young professionals demands more flexibility and the use of digital media. These changes and conditions will shape graduate medical education. On the one hand, medical interventions are becoming increasingly complex, on the other hand patients are getting older and sicker. Therefore, simulation-based learning will play an important role in medical training. © Georg Thieme Verlag Stuttgart · New York.

Structural Asymmetry of the Terminal Catalytic Complex in Selenocysteine Synthesis*

PubMed Central

French, Rachel L.; Gupta, Nirupama; Copeland, Paul R.; Simonović, Miljan

2014-01-01

Selenocysteine (Sec), the 21st amino acid, is synthesized from a serine precursor in a series of reactions that require selenocysteine tRNA (tRNASec). In archaea and eukaryotes, O-phosphoseryl-tRNASec:selenocysteinyl-tRNASec synthase (SepSecS) catalyzes the terminal synthetic reaction during which the phosphoseryl intermediate is converted into the selenocysteinyl moiety while being attached to tRNASec. We have previously shown that only the SepSecS tetramer is capable of binding to and recognizing the distinct fold of tRNASec. Because only two of the four tRNA-binding sites were occupied in the crystal form, a question was raised regarding whether the observed arrangement and architecture faithfully recapitulated the physiologically relevant ribonucleoprotein complex important for selenoprotein formation. Herein, we determined the stoichiometry of the human terminal synthetic complex of selenocysteine by using small angle x-ray scattering, multi-angle light scattering, and analytical ultracentrifugation. In addition, we provided the first estimate of the ratio between SepSecS and tRNASec in vivo. We show that SepSecS preferentially binds one or two tRNASec molecules at a time and that the enzyme is present in large molar excess over the substrate tRNA in vivo. Moreover, we show that in a complex between SepSecS and two tRNAs, one enzyme homodimer plays a role of the noncatalytic unit that positions CCA ends of two tRNASec molecules into the active site grooves of the other, catalytic, homodimer. Finally, our results demonstrate that the previously determined crystal structure represents the physiologically and catalytically relevant complex and suggest that allosteric regulation of SepSecS might play an important role in regulation of selenocysteine and selenoprotein synthesis. PMID:25190812

A trypanosomal orthologue of an intermembrane space chaperone has a non-canonical function in biogenesis of the single mitochondrial inner membrane protein translocase.

PubMed

Wenger, Christoph; Oeljeklaus, Silke; Warscheid, Bettina; Schneider, André; Harsman, Anke

2017-08-01

Mitochondrial protein import is essential for Trypanosoma brucei across its life cycle and mediated by membrane-embedded heterooligomeric protein complexes, which mainly consist of trypanosomatid-specific subunits. However, trypanosomes contain orthologues of small Tim chaperones that escort hydrophobic proteins across the intermembrane space. Here we have experimentally analyzed three novel trypanosomal small Tim proteins, one of which contains only an incomplete Cx3C motif. RNAi-mediated ablation of TbERV1 shows that their import, as in other organisms, depends on the MIA pathway. Submitochondrial fractionation combined with immunoprecipitation and BN-PAGE reveals two pools of small Tim proteins: a soluble fraction forming 70 kDa complexes, consistent with hexamers and a second fraction that is tightly associated with the single trypanosomal TIM complex. RNAi-mediated ablation of the three proteins leads to a growth arrest and inhibits the formation of the TIM complex. In line with these findings, the changes in the mitochondrial proteome induced by ablation of one small Tim phenocopy the effects observed after ablation of TbTim17. Thus, the trypanosomal small Tims play an unexpected and essential role in the biogenesis of the single TIM complex, which for one of them is not linked to import of TbTim17.

NMR studies of protein-nucleic acid interactions.

PubMed

Varani, Gabriele; Chen, Yu; Leeper, Thomas C

2004-01-01

Protein-DNA and protein-RNA complexes play key functional roles in every living organism. Therefore, the elucidation of their structure and dynamics is an important goal of structural and molecular biology. Nuclear magnetic resonance (NMR) studies of protein and nucleic acid complexes have common features with studies of protein-protein complexes: the interaction surfaces between the molecules must be carefully delineated, the relative orientation of the two species needs to be accurately and precisely determined, and close intermolecular contacts defined by nuclear Overhauser effects (NOEs) must be obtained. However, differences in NMR properties (e.g., chemical shifts) and biosynthetic pathways for sample productions generate important differences. Chemical shift differences between the protein and nucleic acid resonances can aid the NMR structure determination process; however, the relatively limited dispersion of the RNA ribose resonances makes the process of assigning intermolecular NOEs more difficult. The analysis of the resulting structures requires computational tools unique to nucleic acid interactions. This chapter summarizes the most important elements of the structure determination by NMR of protein-nucleic acid complexes and their analysis. The main emphasis is on recent developments (e.g., residual dipolar couplings and new Web-based analysis tools) that have facilitated NMR studies of these complexes and expanded the type of biological problems to which NMR techniques of structural elucidation can now be applied.

Elastic Network Model of a Nuclear Transport Complex

NASA Astrophysics Data System (ADS)

Ryan, Patrick; Liu, Wing K.; Lee, Dockjin; Seo, Sangjae; Kim, Young-Jin; Kim, Moon K.

2010-05-01

The structure of Kap95p was obtained from the Protein Data Bank (www.pdb.org) and analyzed RanGTP plays an important role in both nuclear protein import and export cycles. In the nucleus, RanGTP releases macromolecular cargoes from importins and conversely facilitates cargo binding to exportins. Although the crystal structure of the nuclear import complex formed by importin Kap95p and RanGTP was recently identified, its molecular mechanism still remains unclear. To understand the relationship between structure and function of a nuclear transport complex, a structure-based mechanical model of Kap95p:RanGTP complex is introduced. In this model, a protein structure is simply modeled as an elastic network in which a set of coarse-grained point masses are connected by linear springs representing biochemical interactions at atomic level. Harmonic normal mode analysis (NMA) and anharmonic elastic network interpolation (ENI) are performed to predict the modes of vibrations and a feasible pathway between locked and unlocked conformations of Kap95p, respectively. Simulation results imply that the binding of RanGTP to Kap95p induces the release of the cargo in the nucleus as well as prevents any new cargo from attaching to the Kap95p:RanGTP complex.

Heart rate complexity in sinoaortic-denervated mice.

PubMed

Silva, Luiz Eduardo V; Rodrigues, Fernanda Luciano; de Oliveira, Mauro; Salgado, Hélio Cesar; Fazan, Rubens

2015-02-01

What is the central question of this study? New measurements for cardiovascular complexity, such as detrended fluctuation analysis (DFA) and multiscale entropy (MSE), have been shown to predict cardiovascular outcomes. Given that cardiovascular diseases are accompanied by autonomic imbalance and decreased baroreflex sensitivity, the central question is: do baroreceptors contribute to cardiovascular complexity? What is the main finding and its importance? Sinoaortic denervation altered both DFA scaling exponents and MSE, indicating that both short- and long-term mechanisms of complexity are altered in sinoaortic denervated mice, resulting in a loss of physiological complexity. These results suggest that the baroreflex is a key element in the complex structures involved in heart rate variability regulation. Recently, heart rate (HR) oscillations have been recognized as complex behaviours derived from non-linear processes. Physiological complexity theory is based on the idea that healthy systems present high complexity, i.e. non-linear, fractal variability at multiple scales, with long-range correlations. The loss of complexity in heart rate variability (HRV) has been shown to predict adverse cardiovascular outcomes. Based on the idea that most cardiovascular diseases are accompanied by autonomic imbalance and a decrease in baroreflex sensitivity, we hypothesize that the baroreflex plays an important role in complex cardiovascular behaviour. Mice that had been subjected to sinoaortic denervation (SAD) were implanted with catheters in the femoral artery and jugular vein 5 days prior to the experiment. After recording the baseline arterial pressure (AP), pulse interval time series were generated from the intervals between consecutive values of diastolic pressure. The complexity of the HRV was determined using detrended fluctuation analysis and multiscale entropy. The detrended fluctuation analysis α1 scaling exponent (a short-term index) was remarkably decreased in the SAD mice (0.79 ± 0.06 versus 1.13 ± 0.04 for the control mice), whereas SAD slightly increased the α2 scaling exponent (a long-term index; 1.12 ± 0.03 versus 1.04 ± 0.02 for control mice). In the SAD mice, the total multiscale entropy was decreased (13.2 ± 1.3) compared with the control mice (18.9 ± 1.4). In conclusion, fractal and regularity structures of HRV are altered in SAD mice, affecting both short- and long-term mechanisms of complexity, suggesting that the baroreceptors play a considerable role in the complex structure of HRV. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Gout and Metabolic Syndrome: a Tangled Web.

PubMed

Thottam, Gabrielle E; Krasnokutsky, Svetlana; Pillinger, Michael H

2017-08-26

The complexity of gout continues to unravel with each new investigation. Gout sits at the intersection of multiple intrinsically complex processes, and its prevalence, impact on healthcare costs, and association with important co-morbidities make it increasingly relevant. The association between gout and type 2 diabetes, hypertension, hyperlipidemia, cardiovascular disease, renal disease, and obesity suggest that either gout, or its necessary precursor hyperuricemia, may play an important role in the manifestations of the metabolic syndrome. In this review, we analyze the complex interconnections between gout and metabolic syndrome, by reviewing gout's physiologic and epidemiologic relationships with its major co-morbidities. Increasing evidence supports gout's association with metabolic syndrome. More specifically, both human studies and animal models suggest that hyperuricemia may play a role in promoting inflammation, hypertension and cardiovascular disease, adipogenesis and lipogenesis, insulin and glucose dysregulation, and liver disease. Fructose ingestion is associated with increased rates of hypertension, weight gain, impaired glucose tolerance, and dyslipidemia and is a key driver of urate biosynthesis. AMP kinase (AMPK) is a central regulator of processes that tend to mitigate against the metabolic syndrome. Within hepatocytes, leukocytes, and other cells, a fructose/urate metabolic loop drives key inhibitors of AMPK, including AMP deaminase and fructokinase, that may tilt the balance toward metabolic syndrome progression. Preliminary evidence suggests that agents that block the intracellular synthesis of urate may restore AMPK activity and help maintain metabolic homeostasis. Gout is both an inflammatory and a metabolic disease. With further investigation of urate's role, the possibility of proper gout management additionally mitigating metabolic syndrome is an evolving and important question.

Distinct Roles of Velvet Complex in the Development, Stress Tolerance, and Secondary Metabolism in Pestalotiopsis microspora, a Taxol Producer

PubMed Central

Akhberdi, Oren; Zhang, Qian; Wang, Dan; Wang, Haichuan; Hao, Xiaoran; Liu, Yanjie; Wei, Dongsheng; Zhu, Xudong

2018-01-01

The velvet family proteins have been shown to play critical roles in fungal secondary metabolism and development. However, variations of the roles have been observed in different fungi. We report here the observation on the role of three velvet complex components VeA, VelB, and LaeA in Pestalotiopsis microspora, a formerly reported taxol-producing fungus. Deletion of individual members led to the retardation of vegetative growth and sporulation and pigmentation, suggesting critical roles in these processes. The mutant strain △velB appeared hypersensitive to osmotic stress and the dye Congo red, whereas △veA and △laeA were little affected by the pressures, suggesting only velB was required for the integrity of the cell wall. Importantly, we found that the genes played distinct roles in the biosynthesis of secondary metabolites in P. microspora. For instance, the production of pestalotiollide B, a previously characterized polyketide, required velB and laeA. In contrast, the veA gene appeared to inhibit the pestalotiollide B (PB) role in its biosynthesis. This study suggests that the three components of the velvet complex are important global regulators, but with distinct roles in hyphal growth, asexual production, and secondary metabolism in P. microspora. This work provides information for further understanding the biosynthesis of secondary metabolism in the fungus. PMID:29538316

Distinct Roles of Velvet Complex in the Development, Stress Tolerance, and Secondary Metabolism in Pestalotiopsis microspora, a Taxol Producer.

PubMed

Akhberdi, Oren; Zhang, Qian; Wang, Dan; Wang, Haichuan; Hao, Xiaoran; Liu, Yanjie; Wei, Dongsheng; Zhu, Xudong

2018-03-14

The velvet family proteins have been shown to play critical roles in fungal secondary metabolism and development. However, variations of the roles have been observed in different fungi. We report here the observation on the role of three velvet complex components VeA, VelB, and LaeA in Pestalotiopsis microspora , a formerly reported taxol-producing fungus. Deletion of individual members led to the retardation of vegetative growth and sporulation and pigmentation, suggesting critical roles in these processes. The mutant strain △velB appeared hypersensitive to osmotic stress and the dye Congo red, whereas △veA and △laeA were little affected by the pressures, suggesting only velB was required for the integrity of the cell wall. Importantly, we found that the genes played distinct roles in the biosynthesis of secondary metabolites in P. microspora . For instance, the production of pestalotiollide B, a previously characterized polyketide, required velB and laeA . In contrast, the veA gene appeared to inhibit the pestalotiollide B (PB) role in its biosynthesis. This study suggests that the three components of the velvet complex are important global regulators, but with distinct roles in hyphal growth, asexual production, and secondary metabolism in P. microspora . This work provides information for further understanding the biosynthesis of secondary metabolism in the fungus.

Functional inhibition of UQCRB suppresses angiogenesis in zebrafish

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

Cho, Yoon Sun; Jung, Hye Jin; Seok, Seung Hyeok

2013-04-19

Highlights: ► This is the first functional characterization of UQCRB in vivo model. ► Angiogenesis is inhibited with UQCRB loss of function in zebrafish. ► UQCRB is introduced as a prognostic marker for mitochondria- and angiogenesis-related diseases. -- Abstract: As a subunit of mitochondrial complex III, UQCRB plays an important role in complex III stability, electron transport, and cellular oxygen sensing. Herein, we report UQCRB function regarding angiogenesis in vivo with the zebrafish (Danio rerio). UQCRB knockdown inhibited angiogenesis in zebrafish leading to the suppression of VEGF expression. Moreover, the UQCRB-targeting small molecule terpestacin also inhibited angiogenesis and VEGF levelsmore » in zebrafish, supporting the role of UQCRB in angiogenesis. Collectively, UQCRB loss of function by either genetic and pharmacological means inhibited angiogenesis, indicating that UQCRB plays a key role in this process and can be a prognostic marker of angiogenesis- and mitochondria-related diseases.« less

Magnesium degradation as determined by artificial neural networks.

PubMed

Willumeit, Regine; Feyerabend, Frank; Huber, Norbert

2013-11-01

Magnesium degradation under physiological conditions is a highly complex process in which temperature, the use of cell culture growth medium and the presence of CO2, O2 and proteins can influence the corrosion rate and the composition of the resulting corrosion layer. Due to the complexity of this process it is almost impossible to predict the parameters that are most important and whether some parameters have a synergistic effect on the corrosion rate. Artificial neural networks are a mathematical tool that can be used to approximate and analyse non-linear problems with multiple inputs. In this work we present the first analysis of corrosion data obtained using this method, which reveals that CO2 and the composition of the buffer system play a crucial role in the corrosion of magnesium, whereas O2, proteins and temperature play a less prominent role. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Play: early and eternal.

PubMed Central

Mears, C E; Harlow, H F

1975-01-01

A systematic 12-week investigation of development of play behavior was conducted with eight socially reared rhesus monkey infants. A new, basic and primary play form termed self-motion play or peragration was identified and examined. This behavior follows a human model which includes a wide range of pleasurable activities involving motion of the body through space, e.g., rocking, swinging, running, leaping, and water or snow skiing. It can be argued that self-motion play is the initial primate play form and because of its persistence constitutes a reinforcing agent for maintaining many complex patterns and even pastimes. Monkey self-motion play in the present study was divided into five separate patterns in order to compare the relative importance of social and individual peragration play, the role of apparatus and the overall developmental relationships between the different individual and social self-motion play patterns. The data showed that from 90 to 180 days of age self-motion play was independent of other forms of play, that individual self-motion play appeared earlier and with significantly greater increases in frequency than did social self-motion play, and that apparatus was a necessary component for significant increases in social self-motion play. Other findings were that self-motion play existed independent of locomotion and, though initiated by exploration, was separate from it. Therapeutic implications of self-motion play were discussed. Images PMID:1057178

Pokemon (FBI-1) interacts with Smad4 to repress TGF-β-induced transcriptional responses.

PubMed

Yang, Yutao; Cui, Jiajun; Xue, Feng; Zhang, Chuanfu; Mei, Zhu; Wang, Yue; Bi, Mingjun; Shan, Dapeng; Meredith, Alex; Li, Hui; Xu, Zhi-Qing David

2015-03-01

Pokemon, an important proto-oncoprotein, is a transcriptional repressor that belongs to the POK (POZ and Krüppel) family. Smad4, a key component of TGF-β pathway, plays an essential role in TGF-β-induced transcriptional responses. In this study, we show that Pokemon can interact directly with Smad4 both in vitro and in vivo. Overexpression of Pokemon decreases TGF-β-induced transcriptional activities, whereas knockdown of Pokemon increases these activities. Interestingly, Pokemon does not affect activation of Smad2/3, formation of Smads complex, or DNA binding activity of Smad4. TGF-β1 treatment increases the interaction between Pokemon and Smad4, and also enhances the recruitment of Pokemon to Smad4-DNA complex. In addition, we also find that Pokemon recruits HDAC1 to Smad4 complex but decreases the interaction between Smad4 and p300/CBP. Taken together, all these data suggest that Pokemon is a new partner of Smad4 and plays a negative role in TGF-β pathway. Copyright © 2014. Published by Elsevier B.V.

Phase transitions in Pareto optimal complex networks

NASA Astrophysics Data System (ADS)

Seoane, Luís F.; Solé, Ricard

2015-09-01

The organization of interactions in complex systems can be described by networks connecting different units. These graphs are useful representations of the local and global complexity of the underlying systems. The origin of their topological structure can be diverse, resulting from different mechanisms including multiplicative processes and optimization. In spatial networks or in graphs where cost constraints are at work, as it occurs in a plethora of situations from power grids to the wiring of neurons in the brain, optimization plays an important part in shaping their organization. In this paper we study network designs resulting from a Pareto optimization process, where different simultaneous constraints are the targets of selection. We analyze three variations on a problem, finding phase transitions of different kinds. Distinct phases are associated with different arrangements of the connections, but the need of drastic topological changes does not determine the presence or the nature of the phase transitions encountered. Instead, the functions under optimization do play a determinant role. This reinforces the view that phase transitions do not arise from intrinsic properties of a system alone, but from the interplay of that system with its external constraints.

DNA is structured as a linear "jigsaw puzzle" in the genomes of Arabidopsis, rice, and budding yeast.

PubMed

Liu, Yun-Hua; Zhang, Meiping; Wu, Chengcang; Huang, James J; Zhang, Hong-Bin

2014-01-01

Knowledge of how a genome is structured and organized from its constituent elements is crucial to understanding its biology and evolution. Here, we report the genome structuring and organization pattern as revealed by systems analysis of the sequences of three model species, Arabidopsis, rice and yeast, at the whole-genome and chromosome levels. We found that all fundamental function elements (FFE) constituting the genomes, including genes (GEN), DNA transposable elements (DTE), retrotransposable elements (RTE), simple sequence repeats (SSR), and (or) low complexity repeats (LCR), are structured in a nonrandom and correlative manner, thus leading to a hypothesis that the DNA of the species is structured as a linear "jigsaw puzzle". Furthermore, we showed that different FFE differ in their importance in the formation and evolution of the DNA jigsaw puzzle structure between species. DTE and RTE play more important roles than GEN, LCR, and SSR in Arabidopsis, whereas GEN and RTE play more important roles than LCR, SSR, and DTE in rice. The genes having multiple recognized functions play more important roles than those having single functions. These results provide useful knowledge necessary for better understanding genome biology and evolution of the species and for effective molecular breeding of rice.

Divergent Small Tim Homologues Are Associated with TbTim17 and Critical for the Biogenesis of TbTim17 Protein Complexes in Trypanosoma brucei

PubMed Central

Smith, Joseph T.; Singha, Ujjal K.; Misra, Smita

2018-01-01

ABSTRACT The small Tim proteins belong to a group of mitochondrial intermembrane space chaperones that aid in the import of mitochondrial inner membrane proteins with internal targeting signals. Trypanosoma brucei, the protozoan parasite that causes African trypanosomiasis, possesses multiple small Tim proteins that include homologues of T. brucei Tim9 (TbTim9) and Tim10 (TbTim10) and a unique small Tim that shares homology with both Tim8 and Tim13 (TbTim8/13). Here, we found that these three small TbTims are expressed as soluble mitochondrial intermembrane space proteins. Coimmunoprecipitation and mass spectrometry analysis showed that the small TbTims stably associated with each other and with TbTim17, the major component of the mitochondrial inner membrane translocase in T. brucei. Yeast two-hybrid analysis indicated direct interactions among the small TbTims; however, their interaction patterns appeared to be different from those of their counterparts in yeast and humans. Knockdown of the small TbTims reduced cell growth and decreased the steady-state level of TbTim17 and T. brucei ADP/ATP carrier (TbAAC), two polytopic mitochondrial inner membrane proteins. Knockdown of small TbTims also reduced the matured complexes of TbTim17 in mitochondria. Depletion of any of the small TbTims reduced TbTim17 import moderately but greatly hampered the stability of the TbTim17 complexes in T. brucei. Altogether, our results revealed that TbTim9, TbTim10, and TbTim8/13 interact with each other, associate with TbTim17, and play a crucial role in the integrity and maintenance of the levels of TbTim17 complexes. IMPORTANCE Trypanosoma brucei is the causative agent of African sleeping sickness. The parasite’s mitochondrion represents a useful source for potential chemotherapeutic targets. Similarly to yeast and humans, mitochondrial functions depend on the import of proteins that are encoded in the nucleus and made in the cytosol. Even though the machinery involved in this mitochondrial protein import process is becoming clearer in T. brucei, a comprehensive picture of protein complex composition and function is still lacking. In this study, we characterized three T. brucei small Tim proteins, TbTim9, TbTim10, and TbTim8/13. Although the parasite does not have the classical TIM22 complex that imports mitochondrial inner membrane proteins containing internal targeting signals in yeast or humans, we found that these small TbTims associate with TbTim17, the major subunit of the TbTIM complex in T. brucei, and play an essential role in the stability of the TbTim17 complexes. Therefore, these divergent proteins are critical for mitochondrial protein biogenesis in T. brucei. PMID:29925672

Divergent Small Tim Homologues Are Associated with TbTim17 and Critical for the Biogenesis of TbTim17 Protein Complexes in Trypanosoma brucei.

PubMed

Smith, Joseph T; Singha, Ujjal K; Misra, Smita; Chaudhuri, Minu

2018-06-27

The small Tim proteins belong to a group of mitochondrial intermembrane space chaperones that aid in the import of mitochondrial inner membrane proteins with internal targeting signals. Trypanosoma brucei , the protozoan parasite that causes African trypanosomiasis, possesses multiple small Tim proteins that include homologues of T. brucei Tim9 (TbTim9) and Tim10 (TbTim10) and a unique small Tim that shares homology with both Tim8 and Tim13 (TbTim8/13). Here, we found that these three small TbTims are expressed as soluble mitochondrial intermembrane space proteins. Coimmunoprecipitation and mass spectrometry analysis showed that the small TbTims stably associated with each other and with TbTim17, the major component of the mitochondrial inner membrane translocase in T. brucei Yeast two-hybrid analysis indicated direct interactions among the small TbTims; however, their interaction patterns appeared to be different from those of their counterparts in yeast and humans. Knockdown of the small TbTims reduced cell growth and decreased the steady-state level of TbTim17 and T. brucei ADP/ATP carrier (TbAAC), two polytopic mitochondrial inner membrane proteins. Knockdown of small TbTims also reduced the matured complexes of TbTim17 in mitochondria. Depletion of any of the small TbTims reduced TbTim17 import moderately but greatly hampered the stability of the TbTim17 complexes in T. brucei Altogether, our results revealed that TbTim9, TbTim10, and TbTim8/13 interact with each other, associate with TbTim17, and play a crucial role in the integrity and maintenance of the levels of TbTim17 complexes. IMPORTANCE Trypanosoma brucei is the causative agent of African sleeping sickness. The parasite's mitochondrion represents a useful source for potential chemotherapeutic targets. Similarly to yeast and humans, mitochondrial functions depend on the import of proteins that are encoded in the nucleus and made in the cytosol. Even though the machinery involved in this mitochondrial protein import process is becoming clearer in T. brucei , a comprehensive picture of protein complex composition and function is still lacking. In this study, we characterized three T. brucei small Tim proteins, TbTim9, TbTim10, and TbTim8/13. Although the parasite does not have the classical TIM22 complex that imports mitochondrial inner membrane proteins containing internal targeting signals in yeast or humans, we found that these small TbTims associate with TbTim17, the major subunit of the TbTIM complex in T. brucei , and play an essential role in the stability of the TbTim17 complexes. Therefore, these divergent proteins are critical for mitochondrial protein biogenesis in T. brucei . Copyright © 2018 Smith et al.

"Let's Get Physical": Advantages of a Physical Model over 3D Computer Models and Textbooks in Learning Imaging Anatomy

ERIC Educational Resources Information Center

Preece, Daniel; Williams, Sarah B.; Lam, Richard; Weller, Renate

2013-01-01

Three-dimensional (3D) information plays an important part in medical and veterinary education. Appreciating complex 3D spatial relationships requires a strong foundational understanding of anatomy and mental 3D visualization skills. Novel learning resources have been introduced to anatomy training to achieve this. Objective evaluation of their…

A Comparative Study of the Writing/Spelling Performances of "Normal," Dyslexic, and Dysgraphic Children.

ERIC Educational Resources Information Center

Sovik, Nils; Arntzen, Oddvar

1986-01-01

General movement/feedback theory and a "two-routes" theoretical model were tested on 24 normal, 24 dyslexic, and 24 dysgraphic children. Familiarity of the test items and complexity and length of required movement pattern played an important role in the writing/spelling performance of the nine-year-old subjects defined as dyslexic or dysgraphic.…

Examining the Complexities of Measuring Effectiveness of Online Counselling for Young People Using Routine Evaluation Data

ERIC Educational Resources Information Center

Sefi, Aaron; Hanley, Terry

2012-01-01

As mental health services for young people develop, the need for evaluation and audit to justify expenditure follows suit. Counselling is being provided in more and more schools and community settings across the country, and there is an increasing focus on evidence-based funding. Practice-based evidence has an important role to play in fulfilling…

Preliminary Investigation of Visual Attention to Human Figures in Photographs: Potential Considerations for the Design of Aided AAC Visual Scene Displays

ERIC Educational Resources Information Center

Wilkinson, Krista M.; Light, Janice

2011-01-01

Purpose: Many individuals with complex communication needs may benefit from visual aided augmentative and alternative communication systems. In visual scene displays (VSDs), language concepts are embedded into a photograph of a naturalistic event. Humans play a central role in communication development and might be important elements in VSDs.…

The allosteric communication pathways in KIX domain of CBP.

PubMed

Palazzesi, Ferruccio; Barducci, Alessandro; Tollinger, Martin; Parrinello, Michele

2013-08-27

Allosteric regulation plays an important role in a myriad of biomacromolecular processes. Specifically, in a protein, the process of allostery refers to the transmission of a local perturbation, such as ligand binding, to a distant site. Decades after the discovery of this phenomenon, models built on static images of proteins are being reconsidered with the knowledge that protein dynamics plays an important role in its function. Molecular dynamics simulations are a valuable tool for studying complex biomolecular systems, providing an atomistic description of their structure and dynamics. Unfortunately, their predictive power has been limited by the complexity of the biomolecule free-energy surface and by the length of the allosteric timescale (in the order of milliseconds). In this work, we are able to probe the origins of the allosteric changes that transcription factor mixed lineage leukemia (MLL) causes to the interactions of KIX domain of CREB-binding protein (CBP) with phosphorylated kinase inducible domain (pKID), by combing all-atom molecular dynamics with enhanced sampling methods recently developed in our group. We discuss our results in relation to previous NMR studies. We also develop a general simulations protocol to study allosteric phenomena and many other biological processes that occur in the micro/milliseconds timescale.

Catalytic transformation of dinitrogen into ammonia and hydrazine by iron-dinitrogen complexes bearing pincer ligand

PubMed Central

Kuriyama, Shogo; Arashiba, Kazuya; Nakajima, Kazunari; Matsuo, Yuki; Tanaka, Hiromasa; Ishii, Kazuyuki; Yoshizawa, Kazunari; Nishibayashi, Yoshiaki

2016-01-01

Synthesis and reactivity of iron-dinitrogen complexes have been extensively studied, because the iron atom plays an important role in the industrial and biological nitrogen fixation. As a result, iron-catalyzed reduction of molecular dinitrogen into ammonia has recently been achieved. Here we show that an iron-dinitrogen complex bearing an anionic PNP-pincer ligand works as an effective catalyst towards the catalytic nitrogen fixation, where a mixture of ammonia and hydrazine is produced. In the present reaction system, molecular dinitrogen is catalytically and directly converted into hydrazine by using transition metal-dinitrogen complexes as catalysts. Because hydrazine is considered as a key intermediate in the nitrogen fixation in nitrogenase, the findings described in this paper provide an opportunity to elucidate the reaction mechanism in nitrogenase. PMID:27435503

Whatever happened to "What might have been"? Regrets, happiness, and maturity.

PubMed

King, Laura A; Hicks, Joshua A

2007-10-01

Although lost opportunities and mistaken expectations are unpleasant to think and talk about, these experiences may have a role to play in personality development. Drawing on research using narratives of lost possible selves, the authors review the relations of regrettable experiences to 2 important and independent aspects of maturity, happiness and complexity. Thinking about a lost possible self is related to concurrent regrets, distress, and lowered well-being; however, elaborating on a lost possible self is related, concurrently, to complexity and predicts complexity, prospectively, over time. In this article, the authors describe the role that regrettable experiences have in promoting both happiness and complexity. Finally, expanding on previous work, the authors examine potential affordances of happy maturity and suggest psychological capacities that may promote happy maturity. Copyright 2007 APA, all rights reserved.

Spatial complexity of carcass location influences vertebrate scavenger efficiency and species composition.

PubMed

Smith, Joshua B; Laatsch, Lauren J; Beasley, James C

2017-08-31

Scavenging plays an important role in shaping communities through inter- and intra-specific interactions. Although vertebrate scavenger efficiency and species composition is likely influenced by the spatial complexity of environments, heterogeneity in carrion distribution has largely been disregarded in scavenging studies. We tested this hypothesis by experimentally placing juvenile bird carcasses on the ground and in nests in trees to simulate scenarios of nestling bird carrion availability. We used cameras to record scavengers removing carcasses and elapsed time to removal. Carrion placed on the ground was scavenged by a greater diversity of vertebrates and at > 2 times the rate of arboreal carcasses, suggesting arboreal carrion may represent an important resource to invertebrate scavengers, particularly in landscapes with efficient vertebrate scavenging communities. Nonetheless, six vertebrate species scavenged arboreal carcasses. Rat snakes (Elaphe obsolete), which exclusively scavenged from trees, and turkey vultures (Cathartes aura) were the primary scavengers of arboreal carrion, suggesting such resources are potentially an important pathway of nutrient acquisition for some volant and scansorial vertebrates. Our results highlight the intricacy of carrion-derived food web linkages, and how consideration of spatial complexity in carcass distribution (i.e., arboreal) may reveal important pathways of nutrient acquisition by invertebrate and vertebrate scavenging guilds.

Role of membrane contact sites in protein import into mitochondria

PubMed Central

Horvath, Susanne E; Rampelt, Heike; Oeljeklaus, Silke; Warscheid, Bettina; van der Laan, Martin; Pfanner, Nikolaus

2015-01-01

Mitochondria import more than 1,000 different proteins from the cytosol. The proteins are synthesized as precursors on cytosolic ribosomes and are translocated by protein transport machineries of the mitochondrial membranes. Five main pathways for protein import into mitochondria have been identified. Most pathways use the translocase of the outer mitochondrial membrane (TOM) as the entry gate into mitochondria. Depending on specific signals contained in the precursors, the proteins are subsequently transferred to different intramitochondrial translocases. In this article, we discuss the connection between protein import and mitochondrial membrane architecture. Mitochondria possess two membranes. It is a long-standing question how contact sites between outer and inner membranes are formed and which role the contact sites play in the translocation of precursor proteins. A major translocation contact site is formed between the TOM complex and the presequence translocase of the inner membrane (TIM23 complex), promoting transfer of presequence-carrying preproteins to the mitochondrial inner membrane and matrix. Recent findings led to the identification of contact sites that involve the mitochondrial contact site and cristae organizing system (MICOS) of the inner membrane. MICOS plays a dual role. It is crucial for maintaining the inner membrane cristae architecture and forms contacts sites to the outer membrane that promote translocation of precursor proteins into the intermembrane space and outer membrane of mitochondria. The view is emerging that the mitochondrial protein translocases do not function as independent units, but are embedded in a network of interactions with machineries that control mitochondrial activity and architecture. PMID:25514890

Esophageal cancer alters the expression of nuclear pore complex binding protein Hsc70 and eIF5A-1.

PubMed

Moghanibashi, Mehdi; Rastgar Jazii, Ferdous; Soheili, Zahra-Soheila; Zare, Maryam; Karkhane, Aliasghar; Parivar, Kazem; Mohamadynejad, Parisa

2013-06-01

Nuclear pore complex (NPC) is the only corridor for macromolecules exchange between nucleus and cytoplasm. NPC and its components, nucleoporins, play important role in the diverse physiological processes including macromolecule exchange, chromosome segregation, apoptosis and gene expression. Recent reports also suggest involvement of nucleoporins in carcinogenesis. Applying proteomics, we analyzed expression pattern of the NPC components in a newly established esophageal cancer cell line from Persia (Iran), the high-risk region for esophageal cancer. Our results indicate overexpression of Hsc70 and downregulation of subunit alpha type-3 of proteasome, calpain small subunit 1, and eIF5A-1. Among these proteins, Hsc70 and eIF5A-1 are in direct interaction with NPC and involved in the nucleocytoplasmic exchange. Hsc70 plays a critical role as a chaperone in the formation of a cargo-receptor complex in nucleocytoplasmic transport. On the other hand, it is an NPC-associated protein that binds to nucleoporins and contributes in recycling of the nucleocytoplasmic transport receptors in mammals and affects transport of proteins between nucleus and cytoplasm. The other nuclear pore interacting protein: eIF5A-1 binds to the several nucleoporins and participates in nucleocytoplasmic transport. Altered expression of Hsc70 and eIF5A-1 may cause defects in nucleocytoplasmic transport and play a role in esophageal carcinogenesis.

A Chemokine Receptor CXCR2 Macromolecular Complex Regulates Neutrophil Functions in Inflammatory Diseases*

PubMed Central

Wu, Yanning; Wang, Shuo; Farooq, Shukkur M.; Castelvetere, Marcello P.; Hou, Yuning; Gao, Ji-Liang; Navarro, Javier V.; Oupicky, David; Sun, Fei; Li, Chunying

2012-01-01

Inflammation plays an important role in a wide range of human diseases such as ischemia-reperfusion injury, arteriosclerosis, cystic fibrosis, inflammatory bowel disease, etc. Neutrophilic accumulation in the inflamed tissues is an essential component of normal host defense against infection, but uncontrolled neutrophilic infiltration can cause progressive damage to the tissue epithelium. The CXC chemokine receptor CXCR2 and its specific ligands have been reported to play critical roles in the pathophysiology of various inflammatory diseases. However, it is unclear how CXCR2 is coupled specifically to its downstream signaling molecules and modulates cellular functions of neutrophils. Here we show that the PDZ scaffold protein NHERF1 couples CXCR2 to its downstream effector phospholipase C (PLC)-β2, forming a macromolecular complex, through a PDZ-based interaction. We assembled a macromolecular complex of CXCR2·NHERF1·PLC-β2 in vitro, and we also detected such a complex in neutrophils by co-immunoprecipitation. We further observed that the CXCR2-containing macromolecular complex is critical for the CXCR2-mediated intracellular calcium mobilization and the resultant migration and infiltration of neutrophils, as disrupting the complex with a cell permeant CXCR2-specific peptide (containing the PDZ motif) inhibited intracellular calcium mobilization, chemotaxis, and transepithelial migration of neutrophils. Taken together, our data demonstrate a critical role of the PDZ-dependent CXCR2 macromolecular signaling complex in regulating neutrophil functions and suggest that targeting the CXCR2 multiprotein complex may represent a novel therapeutic strategy for certain inflammatory diseases. PMID:22203670

Regulation of Nuclear Import and Export of Negative Cofactor 2*S⃞

PubMed Central

Kahle, Joerg; Piaia, Elisa; Neimanis, Sonja; Meisterernst, Michael; Doenecke, Detlef

2009-01-01

The negative cofactor 2 (NC2) is a protein complex composed of two subunits, NC2α and NC2β, and plays a key role in transcription regulation. Here we investigate whether each subunit contains a nuclear localization signal (NLS) that permits individual crossing of the nuclear membrane or whether nuclear import of NC2α and NC2β depends on heterodimerization. Our results from in vitro binding studies and transfection experiments in cultured cells show that each subunit contains a classical NLS (cNLS) that is recognized by the importin α/β heterodimer. Regardless of the individual cNLSs the two NC2 subunits are translocated as a preassembled complex as co-transfection experiments with wild-type and cNLS-deficient NC2 subunits demonstrate. Ran-dependent binding of the nuclear export receptor Crm1/exportin 1 confirmed the presence of a leucine-rich nuclear export signal (NES) in NC2β. In contrast, NC2α does not exhibit a NES. Our results from interspecies heterokaryon assays suggest that heterodimerization with NC2α masks the NES in NC2β, which prevents nuclear export of the NC2 complex. A mutation in either one of the two cNLSs decreases the extent of importin α/β-mediated nuclear import of the NC2 complex. In addition, the NC2 complex can enter the nucleus via a second pathway, facilitated by importin 13. Because importin 13 binds exclusively to the NC2 complex but not to the individual subunits this alternative import pathway depends on sequence elements distributed among the two subunits. PMID:19204005

Mechanobiology of the Meniscus

PubMed Central

McNulty, Amy L.; Guilak, Farshid

2015-01-01

The meniscus plays a critical biomechanical role in the knee, providing load support, joint stability, and congruity. Importantly, growing evidence indicates that the mechanobiologic response of meniscal cells plays a critical role in the physiologic, pathologic, and repair responses of the meniscus. Here we review experimental and theoretical studies that have begun to directly measure the biomechanical effects of joint loading on the meniscus under physiologic and pathologic conditions, showing that the menisci are exposed to high contact stresses, resulting in a complex and nonuniform stress-strain environment within the tissue. By combining microscale measurements of the mechanical properties of meniscal cells and their pericellular and extracellular matrix regions, theoretical and experimental models indicate that the cells in the meniscus are exposed to a complex and inhomogeneous environment of stress, strain, fluid pressure, fluid flow, and a variety of physicochemical factors. Studies across a range of culture systems from isolated cells to tissues have revealed that the biological response of meniscal cells is directly influenced by physical factors, such as tension, compression, and hydrostatic pressure. In addition, these studies have provided new insights into the mechanotransduction mechanisms by which physical signals are converted into metabolic or pro/anti-inflammatory responses. Taken together, these in vivo and in vitro studies show that mechanical factors play an important role in the health, degeneration, and regeneration of the meniscus. A more thorough understanding of the mechanobiologic responses of the meniscus will hopefully lead to therapeutic approaches to prevent degeneration and enhance repair of the meniscus. PMID:25731738

MITD1 is recruited to midbodies by ESCRT-III and participates in cytokinesis

PubMed Central

Lee, Seongju; Chang, Jaerak; Renvoisé, Benoît; Tipirneni, Anita; Yang, Sarah; Blackstone, Craig

2012-01-01

Diverse cellular processes, including multivesicular body formation, cytokinesis, and viral budding, require the sequential functions of endosomal sorting complexes required for transport (ESCRTs) 0 to III. Of these multiprotein complexes, ESCRT-III in particular plays a key role in mediating membrane fission events by forming large, ring-like helical arrays. A number of proteins playing key effector roles, most notably the ATPase associated with diverse cellular activities protein VPS4, harbor present in microtubule-interacting and trafficking molecules (MIT) domains comprising asymmetric three-helical bundles, which interact with helical MIT-interacting motifs in ESCRT-III subunits. Here we assess comprehensively the ESCRT-III interactions of the MIT-domain family member MITD1 and identify strong interactions with charged multivesicular body protein 1B (CHMP1B), CHMP2A, and increased sodium tolerance-1 (IST1). We show that these ESCRT-III subunits are important for the recruitment of MITD1 to the midbody and that MITD1 participates in the abscission phase of cytokinesis. MITD1 also dimerizes through its C-terminal domain. Both types of interactions appear important for the role of MITD1 in negatively regulating the interaction of IST1 with VPS4. Because IST1 binding in turn regulates VPS4, MITD1 may function through downstream effects on the activity of VPS4, which plays a critical role in the processing and remodeling of ESCRT filaments in abscission. PMID:23015756

The formation of prebiotic molecules in star-forming regions

NASA Astrophysics Data System (ADS)

Rivilla, V. M.

New sensitive observations using the current generation of (sub)millimeter telescopes have revealed in several star-forming regions molecular species of different chemical families (e.g. sugars, esters, isocyanates, phosphorus-bearing species) that may play an important role in prebiotic chemistry, and eventually in the origin of life. The observed molecular abundances of complex organic molecules (glycolaldehyde, ethylene glycol and ethyl formate) are better explained by surface-phase chemistry on dust grains, although gas-phase reactions can also play an important role, as in the case of methyl isocyanate. The PO molecule - a basic chemical bond to build-up the backbone of the DNA - has been detected for the first time in star-forming regions. These new observations indicate that phosphorus, a key element for the development of life, is much more abundant in star-forming regions than previously thought.

Evaluating Motivation for the Use of an Electronic Health Record Simulation Game.

PubMed

McLeod, Alexander; Hewitt, Barbara; Gibbs, David; Kristof, Caitlin

2017-01-01

Experiential learning via simulation offers a variety of benefits including reduced risks, repetitive exposure, and mastery of complex processes. How to motivate people to engage in and enjoy playing games is an important concept in the creation of serious games focused on learning new skills. This study sought to determine the motivators that increase users' pleasurable experience when playing an electronic health record simulation game. To examine how intrinsic and extrinsic motivation affected both engagement and enjoyment, we surveyed students of health professions at one university. Results indicate that while both forms of motivation are significant in increasing engagement and enjoyment, extrinsic motivation such as badges, points, and scoreboards were much more important than internal motivations for our participants. These findings have implications for the development of an electronic health record simulation game.

Evaluating Motivation for the Use of an Electronic Health Record Simulation Game

PubMed Central

McLeod, Alexander; Hewitt, Barbara; Gibbs, David; Kristof, Caitlin

2017-01-01

Experiential learning via simulation offers a variety of benefits including reduced risks, repetitive exposure, and mastery of complex processes. How to motivate people to engage in and enjoy playing games is an important concept in the creation of serious games focused on learning new skills. This study sought to determine the motivators that increase users’ pleasurable experience when playing an electronic health record simulation game. To examine how intrinsic and extrinsic motivation affected both engagement and enjoyment, we surveyed students of health professions at one university. Results indicate that while both forms of motivation are significant in increasing engagement and enjoyment, extrinsic motivation such as badges, points, and scoreboards were much more important than internal motivations for our participants. These findings have implications for the development of an electronic health record simulation game. PMID:28566987

Team Creative Environment as a Mediator Between CWX and R&D Team Performance and Moderating Boundary Conditions.

PubMed

Bornay-Barrachina, Mar; Herrero, Inés

2018-01-01

The purpose of this study was to investigate how high-quality dyadic co-worker relationships (CWXs) favour or hinder team performance. Specifically, we examine the role played by CWX, team creative environment, job complexity and task interdependence to achieve higher levels of team performance. We analyse data from 410 individuals belonging to 81 R&D teams in technology sciences to examine the quality of the dyadic relationships between team members under the same supervisor (co-workers) and team performance measured by the number of publications as their research output. Higher levels of team average CWX relationships are positively related to the establishment of a favourable creative team environment, ending into higher levels of team performance. Specifically, the role played by team average CWX in such relationship is stronger when job complexity and task interdependence are also high. Team's output not only depends on the leader and his/her relationships with subordinates but also on quality relationships among team members. CWXs contribute to creative team environments, but they are essential where jobs are complex and tasks are highly dependent. This study provides evidence of the important role played by CWXs in determining a creative environment, irrespective of their leaders. Previous research has provided information about how leader's role affects team outcomes, but the role of dyadic co-worker relationships in a team remains still relatively unknown. Considering job complexity and task interdependence variables, the study provides with a better understanding about how and when high-quality CWXs should be promoted to achieve higher team performance.

Harnessing the Power of Play: Opportunities for Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Mastrangelo, Sonia

2009-01-01

Play is a complex phenomenon that occurs naturally for most children; they move through the various stages of play development and are able to add complexity, imagination, and creativity to their thought processes and actions. However, for many children with autism spectrum disorders (ASD), the various stages of play never truly develop, or occur…

Player Types, Play Styles, and Play Complexity: Updating the Entertainment Grid

ERIC Educational Resources Information Center

Rademacher Mena, Ricardo Javier

2012-01-01

In a previous work the author created the Education and Entertainment Grid by combining various taxonomies from the fields of play and learning. In this paper, a section of this grid known as the Entertainment Grid will be extended by including previously unused elements of Richard Bartle's online player types and Robert Caillois' play complexity.…

Continuum Level Density of a Coupled-Channel System in the Complex Scaling Method

NASA Astrophysics Data System (ADS)

Suzuki, R.; Kruppa, A. T.; Giraud, B. G.; Katō, K.

2008-06-01

We study the continuum level density (CLD) in the formalism of the complex scaling method (CSM) for coupled-channel systems. We apply the formalism to the ^{4}He = [^{3}H + p] + [^3{He} + n] coupled-channel cluster model where there are resonances at low energy. Numerical calculations of the CLD in the CSM with a finite number of L^{2} basis functions are consistent with the exact result calculated from the S-matrix by solving coupled-channel equations. We also study channel densities. In this framework, the extended completeness relation (ECR) plays an important role.

Role of Edges in Complex Network Epidemiology

NASA Astrophysics Data System (ADS)

Zhang, Hao; Jiang, Zhi-Hong; Wang, Hui; Xie, Fei; Chen, Chao

2012-09-01

In complex network epidemiology, diseases spread along contacting edges between individuals and different edges may play different roles in epidemic outbreaks. Quantifying the efficiency of edges is an important step towards arresting epidemics. In this paper, we study the efficiency of edges in general susceptible-infected-recovered models, and introduce the transmission capability to measure the efficiency of edges. Results show that deleting edges with the highest transmission capability will greatly decrease epidemics on scale-free networks. Basing on the message passing approach, we get exact mathematical solution on configuration model networks with edge deletion in the large size limit.

Aerothermal modeling program, phase 1

NASA Technical Reports Server (NTRS)

Srinivasan, R.; Reynolds, R.; Ball, I.; Berry, R.; Johnson, K.; Mongia, H.

1983-01-01

The combustor performance submodels for complex flows are evaluated. The benchmark test cases for complex nonswirling flows are identified and analyzed. The introduction of swirl into the flow creates much faster mixing, caused by radial pressure gradients and increase in turbulence generation. These phenomena are more difficult to predict than the effects due to geometrical streamline curvatures, like the curved duct, and sudden expansion. Flow fields with swirl, both confined and unconfined are studied. The role of the dilution zone to achieve the turbine inlet radial profile plays an important part, therefore temperature field measurements were made in several idealized dilution zone configurations.

Quality of pre-school children's pretend play and subsequent development of semantic organization and narrative re-telling skills.

PubMed

Stagnitti, Karen; Lewis, Fiona M

2015-04-01

This study investigated if the quality of pre-school children's pretend play predicted their semantic organization and narrative re-telling ability when they were in early primary school. It was hypothesized that the elaborateness of a child's play and the child's use of symbols in play were predictors of their semantic organization and narrative re-tell scores of the School Age Oral Language Assessment. Forty-eight children were assessed using the Child-Initiated Pretend Play Assessment when they were aged 4-5 years. Three-to-five years after this assessment their semantic organization and narrative re-telling skills were assessed. Results indicate that the elaborateness of a child's play and their ability to use symbols was predictive of semantic organization skills. Use of symbols in play was the strongest play predictor of narrative re-telling skills. The quality of a pre-school child's ability to elaborate complex sequences in pretend play and use symbols predicted up to 20% of a child's semantic organization and narrative re-telling skills up to 5 years later. The study provides evidence that the quality of pretend play in 4-5 year olds is important for semantic organization and narrative re-telling abilities in the school-aged child.

[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.

Solubility profiles, hydration and desolvation of curcumin complexed with γ-cyclodextrin and hydroxypropyl-γ-cyclodextrin

NASA Astrophysics Data System (ADS)

Shityakov, Sergey; Salmas, Ramin Ekhteiari; Durdagi, Serdar; Roewer, Norbert; Förster, Carola; Broscheit, Jens

2017-04-01

In this study, we investigated curcumin (CUR) solubility profiles and hydration/desolvation effects of this substance formulated with γ-cyclodextrin (γ-CD) and hydroxypropyl-γ-cyclodextrin (HP-γ-CD) excipients. The CUR/HP-γ-CD complex was found to be more stable in solution with the highest apparent stability constant for CUR/HP-γ-CD (Kc = 1.58*104 M-1) as the more soluble form in distilled water. The in silico calculations, including molecular docking, Monte Carlo (MC), and molecular dynamics (MD) simulations, indicated that water molecules play an important role in host-guest complexation mediating the CUR binding to cyclodextrins via hydrogen bond formations. The CUR hydration/desolvation effects contributed to the complex formation by elevating the CUR binding affinity to both CDs. The CUR/HP-γ-CD complex after the CUR hydration was determined with a minimal Gibbs free energy of binding (ΔGbind = -9.93 kcal*mol-1) due to the major hydrophobic (vdW) forces. Overall, the results of this study can aid a development of cyclodextrin-based drug delivery vectors, signifying the importance of water molecules during the formulation processes.

Molecular architecture and function of the SEA complex, a modulator of the TORC1 pathway.

PubMed

Algret, Romain; Fernandez-Martinez, Javier; Shi, Yi; Kim, Seung Joong; Pellarin, Riccardo; Cimermancic, Peter; Cochet, Emilie; Sali, Andrej; Chait, Brian T; Rout, Michael P; Dokudovskaya, Svetlana

2014-11-01

The TORC1 signaling pathway plays a major role in the control of cell growth and response to stress. Here we demonstrate that the SEA complex physically interacts with TORC1 and is an important regulator of its activity. During nitrogen starvation, deletions of SEA complex components lead to Tor1 kinase delocalization, defects in autophagy, and vacuolar fragmentation. TORC1 inactivation, via nitrogen deprivation or rapamycin treatment, changes cellular levels of SEA complex members. We used affinity purification and chemical cross-linking to generate the data for an integrative structure modeling approach, which produced a well-defined molecular architecture of the SEA complex and showed that the SEA complex comprises two regions that are structurally and functionally distinct. The SEA complex emerges as a platform that can coordinate both structural and enzymatic activities necessary for the effective functioning of the TORC1 pathway. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

LINCing complex functions at the nuclear envelope

PubMed Central

Rothballer, Andrea; Schwartz, Thomas U.; Kutay, Ulrike

2013-01-01

Linker of nucleoskeleton and cytoskeleton (LINC) complexes span the double membrane of the nuclear envelope (NE) and physically connect nuclear structures to cytoskeletal elements. LINC complexes are envisioned as force transducers in the NE, which facilitate processes like nuclear anchorage and migration, or chromosome movements. The complexes are built from members of two evolutionary conserved families of transmembrane (TM) proteins, the SUN (Sad1/UNC-84) domain proteins in the inner nuclear membrane (INM) and the KASH (Klarsicht/ANC-1/SYNE homology) domain proteins in the outer nuclear membrane (ONM). In the lumen of the NE, the SUN and KASH domains engage in an intimate assembly to jointly form a NE bridge. Detailed insights into the molecular architecture and atomic structure of LINC complexes have recently revealed the molecular basis of nucleo-cytoskeletal coupling. They bear important implications for LINC complex function and suggest new potential and as yet unexplored roles, which the complexes may play in the cell. PMID:23324460

New Insights into the Role of Pb-BHA Complexes in the Flotation of Tungsten Minerals

NASA Astrophysics Data System (ADS)

Yue, Tong; Han, Haisheng; Hu, Yuehua; Sun, Wei; Li, Xiaodong; Liu, Runqing; Gao, Zhiyong; Wang, Li; Chen, Pan; Zhang, Chenyang; Tian, Mengjie

2017-11-01

Lead ions (lead nitrate) were introduced to modify the surface properties of tungsten minerals, effectively improving the floatability, with benzohydroxamic acid (BHA) serving as the collector. Flotation tests indicated that Pb-BHA complexes were the active species responsible for flotation of the tungsten minerals. The developed Pb-BHA complexes and the novel flotation process effectively increased the recovery of scheelite and wolframite, simplified the technological process, and led to reduced costs. Fourier transform infrared spectra data showed the presence of adsorbed Pb-BHA complexes on the surface of the minerals. The characteristic peaks of BHA shifted by a considerable extent, indicating that chemical adsorption plays an important role in the flotation process. Zeta potential results confirmed physical adsorption of the positively charged Pb-BHA complexes on the mineral surfaces. The synergistic effect between chemical and physical adsorption facilitated the maximum flotation recovery of scheelite and wolframite.

Middle region of FancM interacts with Mhf and Rmi1 in silkworms, a species lacking the Fanconi anaemia (FA) core complex.

PubMed

Sugahara, R; Mon, H; Lee, J M; Kusakabe, T

2014-04-01

The Fanconi anaemia (FA) pathway is responsible for interstrand crosslink (ICL) repair. Among the FA core complex components, FANCM is believed to act as a damage sensor for the ICL-blocked replication fork and also as a molecular platform for FA core complex assembly and interaction with Bloom's syndrome (BS) complex that is thought to play an important role in the processing of DNA structures such as stalled replication forks. In the present study, we found that in silkworms, Bombyx mori, a species lacking the major FA core complex components (FANCA, B, C, E, F, and G), FancM is required for FancD2 monoubiquitination and cell proliferation in the presence of mitomycin C (MMC). Silkworm FancM (BmFancM) was phosphorylated in the middle regions, and the modification was associated with its subcellular localization. In addition, BmFancM interacted with Mhf1, a histone-fold protein, and Rmi1, a subunit of the BS complex, in the different regions. The interaction region containing at least these two protein-binding domains played an essential role in FancM-dependent resistance to MMC. Our results suggest that BmFancM also acts as a platform for recruitment of both the FA protein and the BS protein, although the silkworm genome seems to lose FAAP24, a FancM-binding partner protein in mammals. © 2013 The Royal Entomological Society.

Integrating structure-from-motion photogrammetry with geospatial software as a novel technique for quantifying 3D ecological characteristics of coral reefs

PubMed Central

Delparte, D; Gates, RD; Takabayashi, M

2015-01-01

The structural complexity of coral reefs plays a major role in the biodiversity, productivity, and overall functionality of reef ecosystems. Conventional metrics with 2-dimensional properties are inadequate for characterization of reef structural complexity. A 3-dimensional (3D) approach can better quantify topography, rugosity and other structural characteristics that play an important role in the ecology of coral reef communities. Structure-from-Motion (SfM) is an emerging low-cost photogrammetric method for high-resolution 3D topographic reconstruction. This study utilized SfM 3D reconstruction software tools to create textured mesh models of a reef at French Frigate Shoals, an atoll in the Northwestern Hawaiian Islands. The reconstructed orthophoto and digital elevation model were then integrated with geospatial software in order to quantify metrics pertaining to 3D complexity. The resulting data provided high-resolution physical properties of coral colonies that were then combined with live cover to accurately characterize the reef as a living structure. The 3D reconstruction of reef structure and complexity can be integrated with other physiological and ecological parameters in future research to develop reliable ecosystem models and improve capacity to monitor changes in the health and function of coral reef ecosystems. PMID:26207190

Cisplatin binds to pre-miR-200b and impairs its processing to mature microRNA.

PubMed

Mezencev, R; Wartell, R M

2018-01-01

Cisplatin is an important anticancer drug with a complex mode of action, a variety of possible targets, and numerous resistance mechanisms. While genomic DNA has traditionally been considered to be its most critical anticancer target, several lines of evidence suggest that various RNAs and other biomolecules may play a role in its anticancer mode of action. In this report we demonstrate that cisplatin modifies pre-miR-200b, impairs its processing to mature miRNA, and decreases miR-200b expression in ovarian cancer cells. Considering the role of miR-200b in epithelial-to-mesenchymal transition and cancer chemosensitivity, cisplatin-induced modification of pre-miR-200b and subsequent deregulation of mature miR-200b may, depending on cell context, limit anticancer activity of this important anticancer drug. More gener- ally, precursor miRNAs may be important targets of cisplatin and play a role in this drug's anticancer activity or modulate cell responses to this drug.

Taxonomy, Physiology, and Natural Products of Actinobacteria.

PubMed

Barka, Essaid Ait; Vatsa, Parul; Sanchez, Lisa; Gaveau-Vaillant, Nathalie; Jacquard, Cedric; Meier-Kolthoff, Jan P; Klenk, Hans-Peter; Clément, Christophe; Ouhdouch, Yder; van Wezel, Gilles P

2016-03-01

Actinobacteria are Gram-positive bacteria with high G+C DNA content that constitute one of the largest bacterial phyla, and they are ubiquitously distributed in both aquatic and terrestrial ecosystems. Many Actinobacteria have a mycelial lifestyle and undergo complex morphological differentiation. They also have an extensive secondary metabolism and produce about two-thirds of all naturally derived antibiotics in current clinical use, as well as many anticancer, anthelmintic, and antifungal compounds. Consequently, these bacteria are of major importance for biotechnology, medicine, and agriculture. Actinobacteria play diverse roles in their associations with various higher organisms, since their members have adopted different lifestyles, and the phylum includes pathogens (notably, species of Corynebacterium, Mycobacterium, Nocardia, Propionibacterium, and Tropheryma), soil inhabitants (e.g., Micromonospora and Streptomyces species), plant commensals (e.g., Frankia spp.), and gastrointestinal commensals (Bifidobacterium spp.). Actinobacteria also play an important role as symbionts and as pathogens in plant-associated microbial communities. This review presents an update on the biology of this important bacterial phylum. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Taxonomy, Physiology, and Natural Products of Actinobacteria

PubMed Central

Vatsa, Parul; Sanchez, Lisa; Gaveau-Vaillant, Nathalie; Jacquard, Cedric; Klenk, Hans-Peter; Clément, Christophe; Ouhdouch, Yder

2015-01-01

SUMMARY Actinobacteria are Gram-positive bacteria with high G+C DNA content that constitute one of the largest bacterial phyla, and they are ubiquitously distributed in both aquatic and terrestrial ecosystems. Many Actinobacteria have a mycelial lifestyle and undergo complex morphological differentiation. They also have an extensive secondary metabolism and produce about two-thirds of all naturally derived antibiotics in current clinical use, as well as many anticancer, anthelmintic, and antifungal compounds. Consequently, these bacteria are of major importance for biotechnology, medicine, and agriculture. Actinobacteria play diverse roles in their associations with various higher organisms, since their members have adopted different lifestyles, and the phylum includes pathogens (notably, species of Corynebacterium, Mycobacterium, Nocardia, Propionibacterium, and Tropheryma), soil inhabitants (e.g., Micromonospora and Streptomyces species), plant commensals (e.g., Frankia spp.), and gastrointestinal commensals (Bifidobacterium spp.). Actinobacteria also play an important role as symbionts and as pathogens in plant-associated microbial communities. This review presents an update on the biology of this important bacterial phylum. PMID:26609051

Inorganic chemistry in nuclear imaging and radiotherapy: current and future directions

PubMed Central

Carroll, Valerie; Demoin, Dustin W.; Hoffman, Timothy J; Jurisson, Silvia S

2013-01-01

Summary Radiometals play an important role in diagnostic and therapeutic radiopharmaceuticals. This field of radiochemistry is multidisciplinary, involving radiometal production, separation of the radiometal from its target, chelate design for complexing the radiometal in a biologically stable environment, specific targeting of the radiometal to its in vivo site, and nuclear imaging and/or radiotherapy applications of the resultant radiopharmaceutical. The critical importance of inorganic chemistry in the design and application of radiometal-containing imaging and therapy agents is described from a historical perspective to future directions. PMID:25382874

TWT transmitter fault prediction based on ANFIS

NASA Astrophysics Data System (ADS)

Li, Mengyan; Li, Junshan; Li, Shuangshuang; Wang, Wenqing; Li, Fen

2017-11-01

Fault prediction is an important component of health management, and plays an important role in the reliability guarantee of complex electronic equipments. Transmitter is a unit with high failure rate. The cathode performance of TWT is a common fault of transmitter. In this dissertation, a model based on a set of key parameters of TWT is proposed. By choosing proper parameters and applying adaptive neural network training model, this method, combined with analytic hierarchy process (AHP), has a certain reference value for the overall health judgment of TWT transmitters.

Contact Angle of Drops Measured on Nontransparent Surfaces and Capillary Flow Visualized

NASA Technical Reports Server (NTRS)

Chao, David F.; Zhang, Nengli

2003-01-01

The spreading of a liquid on a solid surface is important for various practical processes, and contact-angle measurements provide an elegant method to characterize the interfacial properties of the liquid with the solid substrates. The complex physical processes occurring when a liquid contacts a solid play an important role in determining the performance of chemical processes and materials. Applications for these processes are in printing, coating, gluing, textile dyeing, and adhesives and in the pharmaceutical industry, biomedical research, adhesives, flat panel display manufacturing, surfactant chemistry, and thermal engineering.

Stimulus control: Part II

PubMed Central

Dinsmoor, James A.

1995-01-01

The second part of my tutorial stresses the systematic importance of two parameters of discrimination training: (a) the magnitude of the physical difference between the positive and the negative stimulus (disparity) and (b) the magnitude of the difference between the positive stimulus, in particular, and the background stimulation (salience). It then examines the role these variables play in such complex phenomena as blocking and overshadowing, progressive discrimination training, and the transfer of control by fading. It concludes by considering concept formation and imitation, which are important forms of application, and recent work on equivalence relations. PMID:22478222

Oxidative Stress and Immune System in Vitiligo and Thyroid Diseases

PubMed Central

Colucci, Roberta; Dragoni, Federica

2015-01-01

Vitiligo is an acquired dermatological disease frequently associated with autoimmune thyroid disorders. Several theories have been proposed so far to unravel the complex vitiligo pathogenesis. Currently, the autocytotoxic and the autoimmune theories are the most accredited hypothesis, since they are sustained by several important clinical and experimental evidences. A growing body of evidences shows that autoimmunity and oxidative stress strictly interact to finally determine melanocyte loss. In this scenario, associated thyroid autoimmunity might play an active and important role in triggering and maintaining the depigmentation process of vitiligo. PMID:25838868

The Future of Computerized Decision Making

DTIC Science & Technology

2014-12-01

complex, historically reserved for governing bodies or market places where the collective human experience and intelligence come to play. Other decision...access. In all cases, we should think about this carefully first: what data are really important for our goals and what data should be ignored or not even...stored? The answer to these questions involves human intelligence and understanding before the data-to-decision process begins.

Molecular basis of atopic dermatitis.

PubMed

Bonness, Sonja; Bieber, Thomas

2007-10-01

Atopic dermatitis is a common chronic inflammatory skin disease and there are numerous publications on this topic. This review will focus on developments in understanding the molecular basis of atopic dermatitis while considering the genetic background, skin barrier impairment, immune system deviation and microbial superinfections. Atopic dermatitis is a complex genetic disease in which gene-gene and gene-environment interactions play a key role. Surprisingly some genetic regions of interest were found to be overlapping with loci identified to play a role in another very common inflammatory skin disease, psoriasis, while no overlap has so far been observed with asthma. Impairment of the skin barrier followed by antigens trespassing seems to play an important role, favouring sensitization via transepidermal penetration which is the focus of current investigations. Superinfections by pathogens such as Staphylococcus aureus due to a weak innate defence seem to be significant in atopic dermatitis as they elicit a strong inflammatory response. Atopic dermatitis is a chronic inflammatory skin disease with a high incidence in school children and adults. Disease pathogenesis is complex and the background is multifactorial, making the underlying predispositions elusive. Understanding new pathogenic pathways may lead to the development of new drugs with enhanced benefit for the patient.

Stress anisotropy analysis and its effect on unconventional resource development in Montney play, Kakwa, Canada

NASA Astrophysics Data System (ADS)

Tak, Heewon; Choi, Jaewon; Jo, Sohyun; Hwang, Sukyeon

2017-04-01

Stress anisotropy analysis is important for estimating both stress regime and fracture geometry for the efficient development of unconventional resources. Despite being within the same play, different areas can have different stress regimes, which can affect drilling decisions. The Montney play is located in Canada between British Columbia and Alberta. In British Columbia it is known for its ductile shale and high horizontal stress anisotropy because of the Rocky Mountains; however, in Alberta, it has different geological characteristics with some studies finding weak horizontal stress anisotropy. Therefore, we studied the horizontal stress anisotropy using full azimuth seismic and well data in the Kakwa area in order to establish a drilling plan. Minimal horizontal anisotropy was discovered within the area and the direction of maximum horizontal anisotropy corresponded with the regional scale (i.e., NE-SW). The induced fractures were assumed to have a normal stress regime because of the large depth (> 3000 m). Additionally, because of the very high brittleness (Young's modulus > 9) and relatively weak horizontal stress anisotropy, the fracture geometry in the Kakwa area was estimated as complex or complex planar, as opposed to simply planar.

FADS gene cluster polymorphisms: important modulators of fatty acid levels and their impact on atopic diseases.

PubMed

Lattka, Eva; Illig, Thomas; Heinrich, Joachim; Koletzko, Berthold

2009-01-01

Long-chain polyunsaturated fatty acids (LC-PUFAs) play an important role in several physiological processes and their concentration in phospholipids has been associated with several complex diseases, such as atopic disease. The level and composition of LC-PUFAs in the human body is highly dependent on their intake in the diet or on the intake of fatty acid precursors, which are endogenously elongated and desaturated to physiologically active LC-PUFAs. The most important enzymes in this reaction cascade are the Delta(5) and Delta(6) desaturase. Several studies in the last few years have revealed that single nucleotide polymorphisms (SNPs) in the 2 desaturase encoding genes (FADS1 and FADS2) are highly associated with the concentration of omega-6 and omega-3 fatty acids, showing that beside nutrition, genetic factors also play an important role in the regulation of LC-PUFAs. This review focuses on current knowledge of the impact of genetic polymorphisms on LC-PUFA metabolism and on their potential role in the development of atopic diseases. Copyright (c) 2009 S. Karger AG, Basel.

Water soluble biocompatible vesicles based on polysaccharides and oligosaccharides inclusion complexes for carotenoid delivery.

PubMed

Polyakov, Nikolay E; Kispert, Lowell D

2015-09-05

Since carotenoids are highly hydrophobic, air- and light-sensitive hydrocarbon compounds, developing methods for increasing their bioavailability and stability towards irradiation and reactive oxygen species is an important goal. Application of inclusion complexes of "host-guest" type with polysaccharides and oligosaccharides such as arabinogalactan, cyclodextrins and glycyrrhizin minimizes the disadvantages of carotenoids when these compounds are used in food processing (colors and antioxidant capacity) as well as for production of therapeutic formulations. Cyclodextrin complexes which have been used demonstrated enhanced storage stability but suffered from poor solubility. Polysaccharide and oligosaccharide based inclusion complexes play an important role in pharmacology by providing increased solubility and stability of lipophilic drugs. In addition they are used as drug delivery systems to increase absorption rate and bioavailability of the drugs. In this review we summarize the existing data on preparation methods, analysis, and chemical reactivity of carotenoids in inclusion complexes with cyclodextrin, arabinogalactan and glycyrrhizin. It was demonstrated that incorporation of carotenoids into the "host" macromolecule results in significant changes in their physical and chemical properties. In particular, polysaccharide complexes show enhanced photostability of carotenoids in water solutions. A significant decrease in the reactivity towards metal ions and reactive oxygen species in solution was also detected. Copyright © 2015 Elsevier Ltd. All rights reserved.

Growth mechanisms of MgO nanocrystals via a sol-gel synthesis using different complexing agents

PubMed Central

2014-01-01

In the preparation of nanostructured materials, it is important to optimize synthesis parameters in order to obtain the desired material. This work investigates the role of complexing agents, oxalic acid and tartaric acid, in the production of MgO nanocrystals. Results from simultaneous thermogravimetric analysis (STA) show that the two different synthesis routes yield precursors with different thermal profiles. It is found that the thermal profiles of the precursors can reveal the effects of crystal growth during thermal annealing. X-ray diffraction confirms that the final products are pure, single phase and of cubic shape. It is also found that complexing agents can affect the rate of crystal growth. The structures of the oxalic acid and tartaric acid as well as the complexation sites play very important roles in the formation of the nanocrystals. The complexing agents influence the rate of growth which affects the final crystallite size of the materials. Surprisingly, it is also found that oxalic acid and tartaric acid act as surfactants inhibiting crystal growth even at a high temperature of 950°C and a long annealing time of 36 h. The crystallite formation routes are proposed to be via linear and branched polymer networks due to the different structures of the complexing agents. PMID:24650322

Interaction Network and Localization of Brucella abortus Membrane Proteins Involved in the Synthesis, Transport, and Succinylation of Cyclic β-1,2-Glucans

PubMed Central

Guidolin, Leticia S.; Morrone Seijo, Susana M.; Guaimas, Francisco F.

2015-01-01

ABSTRACT Cyclic β-1,2-glucans (CβG) are periplasmic homopolysaccharides that play an important role in the virulence and interaction of Brucella with the host. Once synthesized in the cytoplasm by the CβG synthase (Cgs), CβG are transported to the periplasm by the CβG transporter (Cgt) and succinylated by the CβG modifier enzyme (Cgm). Here, we used a bacterial two-hybrid system and coimmunoprecipitation techniques to study the interaction network between these three integral inner membrane proteins. Our results indicate that Cgs, Cgt, and Cgm can form both homotypic and heterotypic interactions. Analyses carried out with Cgs mutants revealed that the N-terminal region of the protein (Cgs region 1 to 418) is required to sustain the interactions with Cgt and Cgm as well as with itself. We demonstrated by single-cell fluorescence analysis that in Brucella, Cgs and Cgt are focally distributed in the membrane, particularly at the cell poles, whereas Cgm is mostly distributed throughout the membrane with a slight accumulation at the poles colocalizing with the other partners. In summary, our results demonstrate that Cgs, Cgt, and Cgm form a membrane-associated biosynthetic complex. We propose that the formation of a membrane complex could serve as a mechanism to ensure the fidelity of CβG biosynthesis by coordinating their synthesis with the transport and modification. IMPORTANCE In this study, we analyzed the interaction and localization of the proteins involved in the synthesis, transport, and modification of Brucella abortus cyclic β-1,2-glucans (CβG), which play an important role in the virulence and interaction of Brucella with the host. We demonstrate that these proteins interact, forming a complex located mainly at the cell poles; this is the first experimental evidence of the existence of a multienzymatic complex involved in the metabolism of osmoregulated periplasmic glucans in bacteria and argues for another example of pole differentiation in Brucella. We propose that the formation of this membrane complex could serve as a mechanism to ensure the fidelity of CβG biosynthesis by coordinating synthesis with the transport and modification. PMID:25733613

Biochemical Reconstitution of the WAVE Regulatory Complex

PubMed Central

Chen, Baoyu; Padrick, Shae B.; Henry, Lisa; Rosen, Michael K.

2014-01-01

The WAVE regulatory complex (WRC) is a 400-KDa heteropentameric protein assembly that plays a central role in controlling actin cytoskeletal dynamics in many cellular processes. The WRC acts by integrating diverse cellular cues and stimulating the actin nucleating activity of the Arp2/3 complex at membranes. Biochemical and biophysical studies of the underlying mechanisms of these processes require large amounts of purified WRC. Recent success in recombinant expression, reconstitution, purification and crystallization of the WRC has greatly advanced our understanding of the inhibition, activation and membrane recruitment mechanisms of this complex. But many important questions remain to be answered. Here we summarize and update the methods developed in our laboratory, which allow reliable and flexible production of tens of milligrams of recombinant WRC of crystallographic quality, sufficient for many biochemical and structural studies. PMID:24630101

The origin of phosphorescence in Iridium (III) complexes. The role of relativistic effects

NASA Astrophysics Data System (ADS)

Cantero-López, Plinio; Páez-Hernández, Dayan; Arratia-Pérez, Ramiro

2017-10-01

A series of luminescent Ir(III) complexes of the type [Ir(F2ppy)2L] (where L = Lpytz , LOMe , Lbut) have been studied using relativistic two-component density functional theory considering the spin-orbit coupling. The absorption spectra of the three complexes were determined. The most important transition appears in the region between 250 and 350 nm, which is in good agreement with the experimental reports. The three complexes show phosphorescent properties due to a metal-ligand charge transfer (MLCT) process, where the spin-orbit coupling (SOC) plays a key role due to the introduction of a zero field splitting (ZFS) and the mixing of states with different spins which contributes to modify the emission selection rule. The lifetimes of the emission processes were calculated, and the values are in the same order of the experimental reports.

The Large Hydrophilic Loop of Presenilin 1 Is Important for Regulating γ-Secretase Complex Assembly and Dictating the Amyloid β Peptide (Aβ) Profile without Affecting Notch Processing*

PubMed Central

Wanngren, Johanna; Frånberg, Jenny; Svensson, Annelie I.; Laudon, Hanna; Olsson, Fredrik; Winblad, Bengt; Liu, Frank; Näslund, Jan; Lundkvist, Johan; Karlström, Helena

2010-01-01

γ-Secretase is an enzyme complex that mediates both Notch signaling and β-amyloid precursor protein (APP) processing, resulting in the generation of Notch intracellular domain, APP intracellular domain, and the amyloid β peptide (Aβ), the latter playing a central role in Alzheimer disease (AD). By a hitherto undefined mechanism, the activity of γ-secretase gives rise to Aβ peptides of different lengths, where Aβ42 is considered to play a particular role in AD. In this study we have examined the role of the large hydrophilic loop (amino acids 320–374, encoded by exon 10) of presenilin 1 (PS1), the catalytic subunit of γ-secretase, for γ-secretase complex formation and activity on Notch and APP processing. Deletion of exon 10 resulted in impaired PS1 endoproteolysis, γ-secretase complex formation, and had a differential effect on Aβ-peptide production. Although the production of Aβ38, Aβ39, and Aβ40 was severely impaired, the effect on Aβ42 was affected to a lesser extent, implying that the production of the AD-related Aβ42 peptide is separate from the production of the Aβ38, Aβ39, and Aβ40 peptides. Interestingly, formation of the intracellular domains of both APP and Notch was intact, implying a differential cleavage activity between the ϵ/S3 and γ sites. The most C-terminal amino acids of the hydrophilic loop were important for regulating APP processing. In summary, the large hydrophilic loop of PS1 appears to differentially regulate the relative production of different Aβ peptides without affecting Notch processing, two parameters of significance when considering γ-secretase as a target for pharmaceutical intervention in AD. PMID:20106965

Probing ‘Spin-Forbidden’ Oxygen Atom Transfer: Gas-Phase Reactions of Chromium-Porphyrin Complexes

PubMed Central

Fornarini, Simonetta; Lanucara, Francesco; Warren, Jeffrey J.

2010-01-01

Oxygen-atom transfer reactions of metalloporphyrin species play an important role in biochemical and synthetic oxidation reactions. An emerging theme in this chemistry is that spin-state changes can play important roles, and a ‘two-state’ reactivity model has been extensively applied especially in iron-porphyrin systems. Herein we explore the gas phase oxygen-atom transfer chemistry of meso-tetrakis(pentafluorophenyl)porphyrin (TPFPP) chromium complexes, as well as some other tetradentate macrocyclic ligands. Electrospray ionization in concert with Fourier transform ion cyclotron resonance (FT-ICR) spectrometry has been used to characterize and observe reactivity of the ionic species [(TPFPP)CrIII]+ (1) and [(TPFPP)CrVO]+ (2). These are an attractive system to examine the effects of spin state change on oxygen atom transfer because the d1 CrV species are doublets while the CrIII complexes have quartet ground states with high-lying doublet excited states. In the gas phase, [(TPFPP)CrIII]+ forms adducts with a variety of neutral donors but O-atom transfer is only observed for NO2. Pyridine N-oxide adducts of 1 do yield 2 upon collision induced dissociation (CID), but the ethylene oxide, DMSO, and TEMPO analogs do not. [(TPFPP)CrVO]+ is shown by its reactivity and by CID experiments to be a terminal metal-oxo with a single vacant coordination site. It also displays limited reaction chemistry, being deoxygenated only by the very potent reductant P(OMe)3. In general, [(TPFPP)CrVO]+ species are much less reactive than the Fe and Mn analogs. Thermochemical analysis of the reactions points towards the involvement of spin issues in the lower observed reactivity of the chromium complexes. PMID:20218631

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.

A Developmental Learning Approach of Mobile Manipulator via Playing

PubMed Central

Wu, Ruiqi; Zhou, Changle; Chao, Fei; Zhu, Zuyuan; Lin, Chih-Min; Yang, Longzhi

2017-01-01

Inspired by infant development theories, a robotic developmental model combined with game elements is proposed in this paper. This model does not require the definition of specific developmental goals for the robot, but the developmental goals are implied in the goals of a series of game tasks. The games are characterized into a sequence of game modes based on the complexity of the game tasks from simple to complex, and the task complexity is determined by the applications of developmental constraints. Given a current mode, the robot switches to play in a more complicated game mode when it cannot find any new salient stimuli in the current mode. By doing so, the robot gradually achieves it developmental goals by playing different modes of games. In the experiment, the game was instantiated into a mobile robot with the playing task of picking up toys, and the game is designed with a simple game mode and a complex game mode. A developmental algorithm, “Lift-Constraint, Act and Saturate,” is employed to drive the mobile robot move from the simple mode to the complex one. The experimental results show that the mobile manipulator is able to successfully learn the mobile grasping ability after playing simple and complex games, which is promising in developing robotic abilities to solve complex tasks using games. PMID:29046632

Recombination, Pairing, and Synapsis of Homologs during Meiosis

PubMed Central

Zickler, Denise; Kleckner, Nancy

2015-01-01

Recombination is a prominent feature of meiosis in which it plays an important role in increasing genetic diversity during inheritance. Additionally, in most organisms, recombination also plays mechanical roles in chromosomal processes, most notably to mediate pairing of homologous chromosomes during prophase and, ultimately, to ensure regular segregation of homologous chromosomes when they separate at the first meiotic division. Recombinational interactions are also subject to important spatial patterning at both early and late stages. Recombination-mediated processes occur in physical and functional linkage with meiotic axial chromosome structure, with interplay in both directions, before, during, and after formation and dissolution of the synaptonemal complex (SC), a highly conserved meiosis-specific structure that links homolog axes along their lengths. These diverse processes also are integrated with recombination-independent interactions between homologous chromosomes, nonhomology-based chromosome couplings/clusterings, and diverse types of chromosome movement. This review provides an overview of these diverse processes and their interrelationships. PMID:25986558

Refusing the cure: Sophocles's Philoctetes and the clinical problems of self-injurious spite, shame and forgiveness.

PubMed

Gottlieb, Richard M

2004-06-01

Sophocles's Philoctetes (409 BCE) is a dramatic masterpiece unfamiliar to most analysts. The play presents a complex portrait of self-injurious spite of heroic dimensions as it touches on issues of intense shame, feelings of helplessness and the refusal of forgiveness. Sophocles's protagonist, Philoctetes, is a man who, like some of our patients, refuses to be healed. He intends, through his continued sickness and misery, to exact revenge against those who mistreated him. These are recognizable clinical issues, playing roles in every psychoanalytic treatment, issues that may assume a special importance in protracted, stalemated or aborted analyses. There are patients who damage the analyst by damaging the analysis they are in, a malevolent project often undertaken in revenge for wrongs suffered during childhood. This paper links Sophocles's drama to these vitally important clinical considerations through the discussion of a particular case.

Toward an integrated software platform for systems pharmacology

PubMed Central

Ghosh, Samik; Matsuoka, Yukiko; Asai, Yoshiyuki; Hsin, Kun-Yi; Kitano, Hiroaki

2013-01-01

Understanding complex biological systems requires the extensive support of computational tools. This is particularly true for systems pharmacology, which aims to understand the action of drugs and their interactions in a systems context. Computational models play an important role as they can be viewed as an explicit representation of biological hypotheses to be tested. A series of software and data resources are used for model development, verification and exploration of the possible behaviors of biological systems using the model that may not be possible or not cost effective by experiments. Software platforms play a dominant role in creativity and productivity support and have transformed many industries, techniques that can be applied to biology as well. Establishing an integrated software platform will be the next important step in the field. © 2013 The Authors. Biopharmaceutics & Drug Disposition published by John Wiley & Sons, Ltd. PMID:24150748

Trafficking Mechanisms Underlying Neuronal Voltage-gated Ion Channel Localization at the Axon Initial Segment

PubMed Central

Vacher, Helene; Trimmer, James S.

2012-01-01

Summary Voltage-gated ion channels are diverse and fundamental determinants of neuronal intrinsic excitability. Voltage-gated K+ (Kv) and Na+ (Nav) channels play complex yet fundamentally important roles in determining intrinsic excitability. The Kv and Nav channels located at the axon initial segment (AIS) play a unique and especially important role in generating neuronal output in the form of anterograde axonal and backpropagating action potentials, Aberrant intrinsic excitability in individual neurons within networks contributes to synchronous neuronal activity leading to seizures. Mutations in ion channel genes gives rise to a variety of seizure-related “Channelopathies”, and many of the ion channel subunits associated with epilepsy mutations are localized at the AIS, making this a hotspot for epileptogenesis. Here we review the cellular mechanisms that underlie the trafficking of Kv and Nav channels found at the AIS, and how Kv and Nav channel mutations associated with epilepsy can alter these processes. PMID:23216576

The association of mammalian DREAM complex and HPV16 E7 proteins

PubMed Central

Rashid, Nurshamimi Nor; Rothan, Hussin A; Yusoff, Mohd Shahrizal Mohd

2015-01-01

The mammalian DREAM (Drosophila, RB, E2F, and Myb) complex was discovered in 2004 by several research groups. It was initially identified in Drosophila followed by Caenorhaditis elegans and later in mammalian cells. The composition of DREAM is temporally regulated during cell cycle; being associated with E2F-4 and either p107 or p130 in G0/G1 (repressive DREAM complexes) and with B-myb transcription factor in S/G2 (activator DREAM complex). High risk human papillomavirus (HPV) E6 and E7 oncoproteins expression are important for malignant transformation of cervical cancer cells. In particular, the E7 of high risk HPV binds to pRB family members (pRB, p107 and p130) for degradation. It has recently been discovered that the p107 and p130 ‘pocket proteins’ are members of mammalian DREAM complexes. With this understanding, we would like to hypothesise the mammalian DREAM complex could plays a critical role for malignant transformation in cervical cancer cells. PMID:26885443

Structure of a C-terminal fragment of its Vps53 subunit suggests similarity of Golgi-associated retrograde protein (GARP) complex to a family of tethering complexes

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

Vasan, Neil; Hutagalung, Alex; Novick, Peter

2010-08-13

The Golgi-associated retrograde protein (GARP) complex is a membrane-tethering complex that functions in traffic from endosomes to the trans-Golgi network. Here we present the structure of a C-terminal fragment of the Vps53 subunit, important for binding endosome-derived vesicles, at a resolution of 2.9 {angstrom}. We show that the C terminus consists of two {alpha}-helical bundles arranged in tandem, and we identify a highly conserved surface patch, which may play a role in vesicle recognition. Mutations of the surface result in defects in membrane traffic. The fold of the Vps53 C terminus is strongly reminiscent of proteins that belong to threemore » other tethering complexes - Dsl1, conserved oligomeric Golgi, and the exocyst - thought to share a common evolutionary origin. Thus, the structure of the Vps53 C terminus suggests that GARP belongs to this family of complexes.« less

Occurrence of amylose-lipid complexes in teff and maize starch biphasic pastes.

PubMed

Wokadala, Obiro Cuthbert; Ray, Suprakas Sinha; Emmambux, Mohammad Naushad

2012-09-01

The occurrence of amylose-lipid complexes was determined in maize and teff starch biphasic pastes i.e. peak viscosity pastes at short and prolonged pasting times. Maize and teff starches were pasted for 11.5 and 130 min with or without added stearic acid followed by thermo-stable alpha-amylase hydrolysis in a rapid visco-analyzer. X-ray diffraction analysis of pastes before and residues after hydrolysis showed crystalline V-amylose diffraction patterns for the starches pasted for a prolonged time with added stearic acid while less distinct V-amylose patterns with non-complexed stearic acid peaks were observed with a short pasting time. Differential scanning calorimetry of pastes before and residues after paste hydrolysis showed that Type I amylose-lipid complexes were formed after pasting for the short duration with added stearic acid, while Type II complexes are formed after pasting for the prolonged time. The present research provides evidence that amylose-lipid complexes play an important role in starch biphasic pasting. Copyright © 2012 Elsevier Ltd. All rights reserved.

Synthesis, characterization, and binding assessment with human serum albumin of three bipyridine lanthanide(III) complexes.

PubMed

Aramesh-Boroujeni, Zahra; Bordbar, Abdol-Khalegh; Khorasani-Motlagh, Mozhgan; Sattarinezhad, Elham; Fani, Najme; Noroozifar, Meissam

2018-05-18

In this work, the terbium(III), dysprosium(III), and ytterbium(III) complexes containing 2, 2'-bipyridine (bpy) ligand have been synthesized and characterized using CHN elemental analysis, FT-IR, UV-Vis and 1 H-NMR techniques and their binding behavior with human serum albumin (HSA) was studied by UV-Vis, fluorescence and molecular docking examinations. The experimental data indicated that all three lanthanide complexes have high binding affinity to HSA with effective quenching of HSA fluorescence via static mechanism. The binding parameters, the type of interaction, the value of resonance energy transfer, and the binding distance between complexes and HSA were estimated from the analysis of fluorescence measurements and Förster theory. The thermodynamic parameters suggested that van der Waals interactions and hydrogen bonds play an important role in the binding mechanism. While, the energy transfer from HSA molecules to all these complexes occurs with high probability, the order of binding constants (BpyTb > BpyDy > BpyYb) represents the importance of radius of Ln 3+ ion in the complex-HSA interaction. The results of molecular docking calculation and competitive experiments assessed site 3 of HSA, located in subdomain IB, as the most probable binding site for these ligands and also indicated the microenvironment residues around the bound mentioned complexes. The computational results kept in good agreement with experimental data.

Neuroscience of water molecules: a salute to professor Linus Carl Pauling.

PubMed

Nakada, Tsutomu

2009-04-01

More than 35 years ago double Nobel laureate Linus Carl Pauling published a powerful model of the molecular mechanism of general anesthesia, generally referred to as the hydrate-microcrystal (aqueous-phase) theory. This hypothesis, based on the molecular behavior of water molecules, did not receive serious attention during Pauling's life time, when scientific tools for examining complex systems such as the brain were still in their infancy. The situation has since drastically changed, and, now, in the twenty first century, many scientific tools are available for examining different types of complex systems. The discovery of aquaporin-4, a subtype of water channel abundantly expressed in glial systems, further highlighted the concept that the dynamics of water molecules in the cerebral cortex play an important role in important physiological brain functions including consciousness and information processing.

Information flow in the pharmaceutical supply chain.

PubMed

Yousefi, Nazila; Alibabaei, Ahmad

2015-01-01

Managing the supply chain plays an important role in creating competitive advantages for companies. Adequate information flow in supply chain is one of the most important issues in SCM. Therefore, using certain Information Systems can have a significant role in managing and integrating data and information within the supply chain. Pharmaceutical supply chain is more complex than many other supply chains, in the sense that it can affect social and political perspectives. On the other hand, managing the pharmaceutical supply chain is difficult because of its complexity and also government regulations in this field. Although, Iran has progressed a lot in pharmaceutical manufacturing, still there are many unsolved issues in managing the information flow in the pharmaceutical supply chain. In this study, we reviewed the benefits of using different levels of an integrated information system in the supply chain and the possible challenges ahead.

Water and complex organic molecules in the warm inner regions of solar-type protostars

NASA Astrophysics Data System (ADS)

Coutens, A.; Jørgensen, J. K.; Persson, M. V.; Lykke, J. M.; Taquet, V.; van Dishoeck, E. F.; Vastel, C.; Wampfler, S. F.

2015-12-01

Water and complex organic molecules play an important role in the emergence of Life. They have been detected in different types of astrophysical environments (protostars, prestellar cores, outflows, protoplanetary disks, comets, etc). In particular, they show high abundances towards the warm inner regions of protostars, where the icy grain mantles thermally desorb. Can a part of the molecular content observed in these regions be preserved during the star formation process and incorporated into asteroids and comets, that can deliver it to planetary embryos through impacts? By comparison with cometary studies, interferometric observations of solar-type protostars can help to address this important question. We present recent results obtained with the Plateau de Bure interferometer about water deuteration, glycolaldehyde and ethylene glycol towards the low-mass protostar NGC 1333 IRAS2A.

Emergence of complex chemistry on an organic monolayer.

PubMed

Prins, Leonard J

2015-07-21

In many origin-of-life scenarios, inorganic materials, such as FeS or mineral clays, play an important role owing to their ability to concentrate and select small organic molecules on their surface and facilitate their chemical transformations into new molecules. However, considering that life is made up of organic matter, at a certain stage during the evolution the role of the inorganic material must have been taken over by organic molecules. How this exactly happened is unclear, and, indeed, a big gap separates the rudimentary level of organization involving inorganic materials and the complex organization of cells, which are the building blocks of life. Over the past years, we have extensively studied the interaction of small molecules with monolayer-protected gold nanoparticles (Au NPs) for the purpose of developing innovative sensing and catalytic systems. During the course of these studies, we realized that the functional role of this system is very similar to that typically attributed to inorganic surfaces in the early stages of life, with the important being difference that the functional properties (molecular recognition, catalysis, signaling, adaptation) originate entirely from the organic monolayer rather than the inorganic support. This led us to the proposition that this system may serve as a model that illustrates how the important role of inorganic surfaces in dictating chemical processes in the early stages of life may have been taken over by organic matter. Here, we reframe our previously obtained results in the context of the origin-of-life question. The following functional roles of Au NPs will be discussed: the ability to concentrate small molecules and create different local populations, the ability to catalyze the chemical transformation of bound molecules, and, finally, the ability to install rudimentary signaling pathways and display primitive adaptive behavior. In particular, we will show that many of the functional properties of the system originate from two features: the presence of metal ions that are complexed in the organic monolayer and the multivalent nature of the system. Complexed metal ions play an important role in determining the affinity and selectivity of the interaction with small molecules, but serve also as regulatory elements for determining how many molecules are bound simultaneously. Importantly, neighboring metal ion complexes also create catalytic pockets in which two metal ions cooperatively catalyze the cleavage of an RNA-model compound. The multivalent nature of the system permits multiple noncovalent interactions with small molecules that enhances the affinity, but is also at the basis of simple signal transduction pathways and adaptive behavior.

Effect of interaction strength on robustness of controlling edge dynamics in complex networks

NASA Astrophysics Data System (ADS)

Pang, Shao-Peng; Hao, Fei

2018-05-01

Robustness plays a critical role in the controllability of complex networks to withstand failures and perturbations. Recent advances in the edge controllability show that the interaction strength among edges plays a more important role than network structure. Therefore, we focus on the effect of interaction strength on the robustness of edge controllability. Using three categories of all edges to quantify the robustness, we develop a universal framework to evaluate and analyze the robustness in complex networks with arbitrary structures and interaction strengths. Applying our framework to a large number of model and real-world networks, we find that the interaction strength is a dominant factor for the robustness in undirected networks. Meanwhile, the strongest robustness and the optimal edge controllability in undirected networks can be achieved simultaneously. Different from the case of undirected networks, the robustness in directed networks is determined jointly by the interaction strength and the network's degree distribution. Moreover, a stronger robustness is usually associated with a larger number of driver nodes required to maintain full control in directed networks. This prompts us to provide an optimization method by adjusting the interaction strength to optimize the robustness of edge controllability.

Innovation and nested preferential growth in chess playing behavior

NASA Astrophysics Data System (ADS)

Perotti, J. I.; Jo, H.-H.; Schaigorodsky, A. L.; Billoni, O. V.

2013-11-01

Complexity develops via the incorporation of innovative properties. Chess is one of the most complex strategy games, where expert contenders exercise decision making by imitating old games or introducing innovations. In this work, we study innovation in chess by analyzing how different move sequences are played at the population level. It is found that the probability of exploring a new or innovative move decreases as a power law with the frequency of the preceding move sequence. Chess players also exploit already known move sequences according to their frequencies, following a preferential growth mechanism. Furthermore, innovation in chess exhibits Heaps' law suggesting similarities with the process of vocabulary growth. We propose a robust generative mechanism based on nested Yule-Simon preferential growth processes that reproduces the empirical observations. These results, supporting the self-similar nature of innovations in chess are important in the context of decision making in a competitive scenario, and extend the scope of relevant findings recently discovered regarding the emergence of Zipf's law in chess.

SusG: A Unique Cell-Membrane-Associated [alpha]-Amylase from a Prominent Human Gut Symbiont Targets Complex Starch Molecules

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

Koropatkin, Nicole M.; Smith, Thomas J.

SusG is an {alpha}-amylase and part of a large protein complex on the outer surface of the bacterial cell and plays a major role in carbohydrate acquisition by the animal gut microbiota. Presented here, the atomic structure of SusG has an unusual extended, bilobed structure composed of amylase at one end and an unprecedented internal carbohydrate-binding motif at the other. Structural studies further demonstrate that the carbohydrate-binding motif binds maltooligosaccharide distal to, and on the opposite side of, the amylase catalytic site. SusG has an additional starch-binding site on the amylase domain immediately adjacent to the active cleft. Mutagenesis analysismore » demonstrates that these two additional starch-binding sites appear to play a role in catabolism of insoluble starch. However, elimination of these sites has only a limited effect, suggesting that they may have a more important role in product exchange with other Sus components.« less

"Maybe we should talk about it anyway": a qualitative study of understanding expectations and use of an established technology innovation in caring practices.

PubMed

Stokke, Randi

2017-09-15

Technological innovations are strongly promoted to meet the demands posed by increased pressure on home care services and to assist ageing in place in western societies. Although heavily advocated as plug and play solutions, technologies have proven difficult and unpredictable when integrated into home care services. We need greater insight into what happens when technologies are integrated into caring practices. All technologies come with expectations as to their function. This study explores how actors who are involved with the social alarm, which is an established technology innovation, relate to, perceive and articulate these expectations of the technology in everyday living. The article presents results from a two-case study, using a triangulation of qualitative methods in order to gain an in-depth understanding of technology in use in home care services through "thick descriptions". The study was conducted in Norway and data were analysed using a stepwise deductive-inductive analysis. The empirical findings demonstrate that expectations regarding the social alarm, even though it represents a simple and well-established technology, are complex and multidimensional. The notion of script and domestication provided relevant tools for exploring these expectations and for understanding how actors interpret and adapt their practices of using the technology. This enabled a more comprehensive understanding of how technology opens up for different interpretations and puts values in play. This article suggests exploring technology in use as scripted in multidimensional script, and offers a frame for doing so. It also reveals how technology scripts and articulation prove important for understanding the complex reality when integrated into home care practices, thus identifying how using the technology leads to the taming and unleashing of both technology and actors. The study offers an increased understanding of how and why technology is unpredictable and works differently in different contexts. Moreover, it stresses the importance of avoiding expectations of plug-and-play in a reality of complex interactions between different actors.

Spatial complexity of carcass location influences vertebrate scavenger efficiency and species composition

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

Smith, Joshua B.; Laatsch, Lauren J.; Beasley, James C.

Scavenging plays an important role in shaping communities through inter- and intra-specific interactions. Although vertebrate scavenger efficiency and species composition is likely influenced by the spatial complexity of environments, heterogeneity in carrion distribution has largely been disregarded in scavenging studies. We tested this hypothesis by experimentally placing juvenile bird carcasses on the ground and in nests in trees to simulate scenarios of nestling bird carrion availability. We used cameras to record scavengers removing carcasses and elapsed time to removal. Carrion placed on the ground was scavenged by a greater diversity of vertebrates and at > 2 times the rate ofmore » arboreal carcasses, suggesting arboreal carrion may represent an important resource to invertebrate scavengers, particularly in landscapes with efficient vertebrate scavenging communities. Nonetheless, six vertebrate species scavenged arboreal carcasses. Rat snakes (Elaphe obsolete), which exclusively scavenged from trees, and turkey vultures (Cathartes aura) were the primary scavengers of arboreal carrion, suggesting such resources are potentially an important pathway of nutrient acquisition for some volant and scansorial vertebrates. Our results highlight the intricacy of carrion-derived food web linkages, and how consideration of spatial complexity in carcass distribution (i.e., arboreal) may reveal important pathways of nutrient acquisition by invertebrate and vertebrate scavenging guilds.« less

Interaction of divalent metal ions with human translocase of inner membrane of mitochondria Tim23.

PubMed

Feng, Wei; Zhang, Yongqiang; Deng, Honghua; Li, Shu Jie

2016-06-17

The preprotein translocase of the inner membrane of mitochondria (TIM23 complex) is the main entry gate for proteins of the matrix and the inner membrane. Tim23p, the core component of TIM23 complex, forms the import pore across the inner membrane and exerts a key function in the protein import. However, the interaction of divalent metal ions with Tim23p and the contribution in the interaction of presequence peptide with Tim23p are still unknown. Herein, we investigated the interaction of divalent metal ions with the intermembrane space domain of Tim23p (Tim23IMS) and the interaction of presequence peptides with Tim23IMS in presence of Ca(2+) ion by fluorescence spectroscopy in vitro. The static fluorescence quenching indicates the existence of strong binding between divalent metal ions and Tim23IMS. The order of the binding strength is Ca(2+), Mg(2+), Cu(2+), Mn(2+), and Co(2+) (from strong to weak). Moreover, the interaction of presequence peptides with Tim23IMS is weakened in presence of Ca(2+) ion, which implicates that Ca(2+) ion may play an important role in the protein import by TIM23 complex. Copyright © 2016 Elsevier Inc. All rights reserved.

Spatial complexity of carcass location influences vertebrate scavenger efficiency and species composition

DOE PAGES

Smith, Joshua B.; Laatsch, Lauren J.; Beasley, James C.

2017-08-31

Scavenging plays an important role in shaping communities through inter- and intra-specific interactions. Although vertebrate scavenger efficiency and species composition is likely influenced by the spatial complexity of environments, heterogeneity in carrion distribution has largely been disregarded in scavenging studies. We tested this hypothesis by experimentally placing juvenile bird carcasses on the ground and in nests in trees to simulate scenarios of nestling bird carrion availability. We used cameras to record scavengers removing carcasses and elapsed time to removal. Carrion placed on the ground was scavenged by a greater diversity of vertebrates and at > 2 times the rate ofmore » arboreal carcasses, suggesting arboreal carrion may represent an important resource to invertebrate scavengers, particularly in landscapes with efficient vertebrate scavenging communities. Nonetheless, six vertebrate species scavenged arboreal carcasses. Rat snakes (Elaphe obsolete), which exclusively scavenged from trees, and turkey vultures (Cathartes aura) were the primary scavengers of arboreal carrion, suggesting such resources are potentially an important pathway of nutrient acquisition for some volant and scansorial vertebrates. Our results highlight the intricacy of carrion-derived food web linkages, and how consideration of spatial complexity in carcass distribution (i.e., arboreal) may reveal important pathways of nutrient acquisition by invertebrate and vertebrate scavenging guilds.« less

"Mommy, You Are the Princess and I Am the Queen": How Preschool Children's Initiation and Language Use during Pretend Play Relate to Complexity

ERIC Educational Resources Information Center

Melzer, Dawn K.; Palermo, Cori A.

2016-01-01

The present study investigated the relationship between complexity of pretend play, initiation of pretense activities, and mental state utterances used during play. Children 3 to 4 years of age were videotaped while engaging in pretend play with a parent. The videotapes were coded according to mental state utterances (i.e. desire, emotion,…

A 20-year reassessment of the health and status of whitebark pine forests in the Bob Marshall Wilderness Complex, Montana

Treesearch

Molly L. Retzlaff; Signe B. Leirfallom; Robert E. Keane

2016-01-01

Whitebark pine plays a prominent role in high elevation ecosystems of the northern Rocky Mountains. It is an important food source for many birds and mammals as well as an essential component of watershed stabilization. Whitebark pine is vanishing from the landscape due to three main factors: white pine blister rust, mountain pine beetle outbreaks, and successional...

Toll-like receptors and gastrointestinal diseases: from bench to bedside?

PubMed

Cario, Elke

2002-11-01

The family of Toll-like receptors (TLRs) plays a key role in mediating innate immune responses to numerous luminal commensal- and pathogen-derived pattern molecules by the intestinal mucosa. Recent findings have identified several ligands recognized by TLRs as well as the complex downstream signaling effects resulting from activation of these receptors. Understanding is emerging of the importance of TLRs in mucosal host defense-potentially triggering gastrointestinal diseases.

Electrostatics in pharmaceutical aerosols for inhalation.

PubMed

Wong, Jennifer; Chan, Hak-Kim; Kwok, Philip Chi Lip

2013-08-01

Electrostatics continues to play an important role in pharmaceutical aerosols for inhalation. Despite its ubiquitous nature, the charging process is complex and not well understood. Nonetheless, significant advances in the past few years continue to improve understanding and lead to better control of electrostatics. The purpose of this critical review is to present an overview of the literature, with an emphasis on how electrostatic charge can be useful in improving pulmonary drug delivery.

A Neuronal Model of Classical Conditioning.

DTIC Science & Technology

1987-10-01

animal’s nervous system. This assunption might not hold up well at hiyher, cognitive levels of function but the assumption appears reasonabie as a starting...complex, cognitive phenomena may begin to emerge. To support the process of drive acquisition or learning dt the network level, global centers that...intelligence at higher, cognitive levels. At such levels, explicit teachers play an important role. However, I suggest that this has misled neural

mTORC1 Plays an Important Role in Skeletal Development by Controlling Preosteoblast Differentiation

PubMed Central

Matthews, Mary P.; Martin, Sally K.; Xie, Jianling; Ooi, Soo Siang; Walkley, Carl R.; Codrington, John D.; Ruegg, Markus A.; Hall, Michael N.; Proud, Christopher G.; Gronthos, Stan; Zannettino, Andrew C. W.

2017-01-01

ABSTRACT The mammalian target of rapamycin complex 1 (mTORC1) is activated by extracellular factors that control bone accrual. However, the direct role of this complex in osteoblast biology remains to be determined. To investigate this question, we disrupted mTORC1 function in preosteoblasts by targeted deletion of Raptor (Rptor) in Osterix-expressing cells. Deletion of Rptor resulted in reduced limb length that was associated with smaller epiphyseal growth plates in the postnatal skeleton. Rptor deletion caused a marked reduction in pre- and postnatal bone accrual, which was evident in skeletal elements derived from both intramembranous and endochondrial ossification. The decrease in bone accrual, as well as the associated increase in skeletal fragility, was due to a reduction in osteoblast function. In vitro, osteoblasts derived from knockout mice display a reduced osteogenic potential, and an assessment of bone-developmental markers in Rptor knockout osteoblasts revealed a transcriptional profile consistent with an immature osteoblast phenotype suggesting that osteoblast differentiation was stalled early in osteogenesis. Metabolic labeling and an assessment of cell size of Rptor knockout osteoblasts revealed a significant decrease in protein synthesis, a major driver of cell growth. These findings demonstrate that mTORC1 plays an important role in skeletal development by regulating mRNA translation during preosteoblast differentiation. PMID:28069737

A muscle-specific knockout implicates nuclear receptor coactivator MED1 in the regulation of glucose and energy metabolism.

PubMed

Chen, Wei; Zhang, Xiaoting; Birsoy, Kivanc; Roeder, Robert G

2010-06-01

As conventional transcriptional factors that are activated in diverse signaling pathways, nuclear receptors play important roles in many physiological processes that include energy homeostasis. The MED1 subunit of the Mediator coactivator complex plays a broad role in nuclear receptor-mediated transcription by anchoring the Mediator complex to diverse promoter-bound nuclear receptors. Given the significant role of skeletal muscle, in part through the action of nuclear receptors, in glucose and fatty acid metabolism, we generated skeletal muscle-specific Med1 knockout mice. Importantly, these mice show enhanced insulin sensitivity and improved glucose tolerance as well as resistance to high-fat diet-induced obesity. Furthermore, the white muscle of these mice exhibits increased mitochondrial density and expression of genes specific to type I and type IIA fibers, indicating a fast-to-slow fiber switch, as well as markedly increased expression of the brown adipose tissue-specific UCP-1 and Cidea genes that are involved in respiratory uncoupling. These dramatic results implicate MED1 as a powerful suppressor in skeletal muscle of genetic programs implicated in energy expenditure and raise the significant possibility of therapeutical approaches for metabolic syndromes and muscle diseases through modulation of MED1-nuclear receptor interactions.

A Graph Approach to Mining Biological Patterns in the Binding Interfaces.

PubMed

Cheng, Wen; Yan, Changhui

2017-01-01

Protein-RNA interactions play important roles in the biological systems. Searching for regular patterns in the Protein-RNA binding interfaces is important for understanding how protein and RNA recognize each other and bind to form a complex. Herein, we present a graph-mining method for discovering biological patterns in the protein-RNA interfaces. We represented known protein-RNA interfaces using graphs and then discovered graph patterns enriched in the interfaces. Comparison of the discovered graph patterns with UniProt annotations showed that the graph patterns had a significant overlap with residue sites that had been proven crucial for the RNA binding by experimental methods. Using 200 patterns as input features, a support vector machine method was able to classify protein surface patches into RNA-binding sites and non-RNA-binding sites with 84.0% accuracy and 88.9% precision. We built a simple scoring function that calculated the total number of the graph patterns that occurred in a protein-RNA interface. That scoring function was able to discriminate near-native protein-RNA complexes from docking decoys with a performance comparable with that of a state-of-the-art complex scoring function. Our work also revealed possible patterns that might be important for binding affinity.

Carotenoids, versatile components of oxygenic photosynthesis.

PubMed

Domonkos, Ildikó; Kis, Mihály; Gombos, Zoltán; Ughy, Bettina

2013-10-01

Carotenoids (CARs) are a group of pigments that perform several important physiological functions in all kingdoms of living organisms. CARs serve as protective agents, which are essential structural components of photosynthetic complexes and membranes, and they play an important role in the light harvesting mechanism of photosynthesizing plants and cyanobacteria. The protection against reactive oxygen species, realized by quenching of singlet oxygen and the excited states of photosensitizing molecules, as well as by the scavenging of free radicals, is one of the main biological functions of CARs. X-ray crystallographic localization of CARs revealed that they are present at functionally and structurally important sites of both the PSI and PSII reaction centers. Characterization of a CAR-less cyanobacterial mutant revealed that while the absence of CARs prevents the formation of PSII complexes, it does not abolish the assembly and function of PSI. CAR molecules assist in the formation of protein subunits of the photosynthetic complexes by gluing together their protein components. In addition to their aforementioned indispensable functions, CARs have a substantial role in the formation and maintenance of proper cellular architecture, and potentially also in the protection of the translational machinery under stress conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Traumatized TFCC: An Illustrated Review of the Anatomy and Injury Patterns of the Triangular Fibrocartilage Complex.

PubMed

Skalski, Matthew R; White, Eric A; Patel, Dakshesh B; Schein, Aaron J; RiveraMelo, Hector; Matcuk, George R

2016-01-01

The triangular fibrocartilage complex (TFCC) plays an important role in wrist biomechanics and is prone to traumatic and degenerative injury, making it a common source of ulnar-sided wrist pain. Because of this, the TFCC is frequently imaged, and a detailed understanding of its anatomy and injury patterns is critical in generating an accurate report to help guide treatment. In this review, we provide a detailed overview of TFCC anatomy, its normal appearance on magnetic resonance imaging, the spectrum of TFCC injuries based on the Palmer classification system, and pitfalls in accurate assessment. Copyright © 2015 Mosby, Inc. All rights reserved.

The recovery model and complex health needs: what health psychology can learn from mental health and substance misuse service provision.

PubMed

Webb, Lucy

2012-07-01

This article reviews key arguments around evidence-based practice and outlines the methodological demands for effective adoption of recovery model principles. The recovery model is outlined and demonstrated as compatible with current needs in substance misuse service provision. However, the concepts of evidence-based practice and the recovery model are currently incompatible unless the current value system of evidence-based practice changes to accommodate the methodologies demanded by the recovery model. It is suggested that critical health psychology has an important role to play in widening the scope of evidence-based practice to better accommodate complex social health needs.

Localized motion in random matrix decomposition of complex financial systems

NASA Astrophysics Data System (ADS)

Jiang, Xiong-Fei; Zheng, Bo; Ren, Fei; Qiu, Tian

2017-04-01

With the random matrix theory, we decompose the multi-dimensional time series of complex financial systems into a set of orthogonal eigenmode functions, which are classified into the market mode, sector mode, and random mode. In particular, the localized motion generated by the business sectors, plays an important role in financial systems. Both the business sectors and their impact on the stock market are identified from the localized motion. We clarify that the localized motion induces different characteristics of the time correlations for the stock-market index and individual stocks. With a variation of a two-factor model, we reproduce the return-volatility correlations of the eigenmodes.

Immobilized magnetic beads-based multi-target affinity selection coupled with HPLC-MS for screening active compounds from traditional Chinese medicine and natural products.

PubMed

Chen, Yaqi; Chen, Zhui; Wang, Yi

2015-01-01

Screening and identifying active compounds from traditional Chinese medicine (TCM) and other natural products plays an important role in drug discovery. Here, we describe a magnetic beads-based multi-target affinity selection-mass spectrometry approach for screening bioactive compounds from natural products. Key steps and parameters including activation of magnetic beads, enzyme/protein immobilization, characterization of functional magnetic beads, screening and identifying active compounds from a complex mixture by LC/MS, are illustrated. The proposed approach is rapid and efficient in screening and identification of bioactive compounds from complex natural products.

Unraveling secrets of telomeres: one molecule at a time

PubMed Central

Lin, Jiangguo; Kaur, Parminder; Countryman, Preston; Opresko, Patricia L.; Wang, Hong

2016-01-01

Telomeres play important roles in maintaining the stability of linear chromosomes. Telomere maintenance involves dynamic actions of multiple proteins interacting with long repetitive sequences and complex dynamic DNA structures, such as G-quadruplexes, T-loops and t-circles. Given the heterogeneity and complexity of telomeres, single-molecule approaches are essential to fully understand the structure-function relationships that govern telomere maintenance. In this review, we present a brief overview of the principles of single-molecule imaging and manipulation techniques. We then highlight results obtained from applying these single-molecule techniques for studying structure, dynamics and functions of G-quadruplexes, telomerase, and shelterin proteins. PMID:24569170

[The importance of relationship satisfaction and the questionnaire techniques of its measurement].

PubMed

Vajda, Dóra; Sz Makó, Hajnalka

2014-01-01

The quality of marriage or partnership has an impact on many areas of life. Consequently, a good working relationship can be a significant resource to cope with difficult life situations and stress, and may contribute to partners' well-being and healthy lifestyle. Therefore, its investigation has particular relevance. Relationship satisfaction is a complex concept which is confirmed by both diversity and multidimensionality of its definition. The aim of this study is to provide an overview of the importance of relationship satisfaction, inter- and intrapersonal factors influencing its development, its changes over family life cycles and the gender differences that may manifest in relationship satisfaction. In addition, this review summarizes the questionnaire techniques of measuring relationship satisfaction which are also reflected within the complexity and the diversity of the concept. Given the fact that the degree of relationship satisfaction plays a salient role in many aspects of life, the empirical research findings which emphasize the importance of this conception can serve as an alternative to aim the mobilization of its practical work.

[Elucidation of key genes in sex determination in genetics teaching].

PubMed

Li, Meng; He, Zhumei

2014-06-01

Sex is an important and complex feature of organisms, which is controlled by the genetic and environmental factors. The genetic factors, i.e., genes, are vital in sex determination. However, not all the related genes play the same roles, and some key genes play a vital role in the sex determination and differentiation. With the development of the modern genetics, a great progress on the key genes has been made in sex determination. In this review, we summarize the mechanism of sex determination and the strategy of how to study the key genes in sex determination. It will help us to understand the mechanism of sex determination better in the teaching of genetics.

The Role of Snow and Ice in the Climate System

ScienceCinema

Barry, Roger G.

2017-12-09

Global snow and ice cover (the 'cryosphere') plays a major role in global climate and hydrology through a range of complex interactions and feedbacks, the best known of which is the ice - albedo feedback. Snow and ice cover undergo marked seasonal and long term changes in extent and thickness. The perennial elements - the major ice sheets and permafrost - play a role in present-day regional and local climate and hydrology, but the large seasonal variations in snow cover and sea ice are of importance on continental to hemispheric scales. The characteristics of these variations, especially in the Northern Hemisphere, and evidence for recent trends in snow and ice extent are discussed.

Dramatic performance of Clostridium thermocellum explained by its wide range of cellulase modalities.

PubMed

Xu, Qi; Resch, Michael G; Podkaminer, Kara; Yang, Shihui; Baker, John O; Donohoe, Bryon S; Wilson, Charlotte; Klingeman, Dawn M; Olson, Daniel G; Decker, Stephen R; Giannone, Richard J; Hettich, Robert L; Brown, Steven D; Lynd, Lee R; Bayer, Edward A; Himmel, Michael E; Bomble, Yannick J

2016-02-01

Clostridium thermocellum is the most efficient microorganism for solubilizing lignocellulosic biomass known to date. Its high cellulose digestion capability is attributed to efficient cellulases consisting of both a free-enzyme system and a tethered cellulosomal system wherein carbohydrate active enzymes (CAZymes) are organized by primary and secondary scaffoldin proteins to generate large protein complexes attached to the bacterial cell wall. This study demonstrates that C. thermocellum also uses a type of cellulosomal system not bound to the bacterial cell wall, called the "cell-free" cellulosomal system. The cell-free cellulosome complex can be seen as a "long range cellulosome" because it can diffuse away from the cell and degrade polysaccharide substrates remotely from the bacterial cell. The contribution of these two types of cellulosomal systems in C. thermocellum was elucidated by characterization of mutants with different combinations of scaffoldin gene deletions. The primary scaffoldin, CipA, was found to play the most important role in cellulose degradation by C. thermocellum, whereas the secondary scaffoldins have less important roles. Additionally, the distinct and efficient mode of action of the C. thermocellum exoproteome, wherein the cellulosomes splay or divide biomass particles, changes when either the primary or secondary scaffolds are removed, showing that the intact wild-type cellulosomal system is necessary for this essential mode of action. This new transcriptional and proteomic evidence shows that a functional primary scaffoldin plays a more important role compared to secondary scaffoldins in the proper regulation of CAZyme genes, cellodextrin transport, and other cellular functions.

Thiabendazole inhibits ubiquinone reduction activity of mitochondrial respiratory complex II via a water molecule mediated binding feature.

PubMed

Zhou, Qiangjun; Zhai, Yujia; Lou, Jizhong; Liu, Man; Pang, Xiaoyun; Sun, Fei

2011-07-01

The mitochondrial respiratory complex II or succinate: ubiquinone oxidoreductase (SQR) is a key membrane complex in both the tricarboxylic acid cycle and aerobic respiration. Five disinfectant compounds were investigated with their potent inhibition effects on the ubiquinone reduction activity of the porcine mitochondrial SQR by enzymatic assay and crystallography. Crystal structure of the SQR bound with thiabendazole (TBZ) reveals a different inhibitor-binding feature at the ubiquinone binding site where a water molecule plays an important role. The obvious inhibitory effect of TBZ based on the biochemical data (IC(50) ~100 μmol/L) and the significant structure-based binding affinity calculation (~94 μmol/L) draw the suspicion of using TBZ as a good disinfectant compound for nematode infections treatment and fruit storage.

Analyzing the causation of a railway accident based on a complex network

NASA Astrophysics Data System (ADS)

Ma, Xin; Li, Ke-Ping; Luo, Zi-Yan; Zhou, Jin

2014-02-01

In this paper, a new model is constructed for the causation analysis of railway accident based on the complex network theory. In the model, the nodes are defined as various manifest or latent accident causal factors. By employing the complex network theory, especially its statistical indicators, the railway accident as well as its key causations can be analyzed from the overall perspective. As a case, the “7.23” China—Yongwen railway accident is illustrated based on this model. The results show that the inspection of signals and the checking of line conditions before trains run played an important role in this railway accident. In conclusion, the constructed model gives a theoretical clue for railway accident prediction and, hence, greatly reduces the occurrence of railway accidents.

The role of the medial prefrontal cortex in the play fighting of rats.

PubMed

Bell, Heather C; McCaffrey, David R; Forgie, Margaret L; Kolb, Bryan; Pellis, Sergio M

2009-12-01

Although decorticated rats are able to engage in play, their play is abnormal in three ways. First, decorticates do not display the normal, age-related shifts in defensive strategies during development. Second, decorticates do not modify their defensive tactics in response to the social identity of their partners. Third, decorticates display a global shift in defensive tactics from more complex to less complex strategies. It has been shown that lesions of the motor cortex (MC) selectively produce the abnormal developmental effects on play, and that lesions of the orbitofrontal cortex (OFC) selectively produce the deficits in behavioral discrimination between social partners. In the current set of experiments, we demonstrate that lesions of the medial prefrontal cortex (mPFC) produce the shift from more complex to less complex defensive tactics, while leaving intact the age-related and partner-related modulation of defensive strategies. Thus, we have evidence for a triple dissociation of function between the MC, the OFC, and the mPFC with respect to social play behavior.

Interdependency of formation and localisation of the Min complex controls symmetric plastid division.

PubMed

Maple, Jodi; Møller, Simon G

2007-10-01

Plastid division represents a fundamental biological process essential for plant development; however, the molecular basis of symmetric plastid division is unclear. AtMinE1 plays a pivotal role in selection of the plastid division site in concert with AtMinD1. AtMinE1 localises to discrete foci in chloroplasts and interacts with AtMinD1, which shows a similar localisation pattern. Here, we investigate the importance of Min protein complex formation during the chloroplast division process. Dissection of the assembly of the Min protein complex and determination of the interdependency of complex assembly and localisation in planta allow us to present a model of the molecular basis of selection of the division site in plastids. Moreover, functional analysis of AtMinE1 in bacteria demonstrates the level of functional conservation and divergence of the plastidic MinE proteins.

Solvent-induced assembly of two helical Eu(III) metal-organic frameworks and fluorescence sensing activities towards nitrobenzene and Cu2+ ions

NASA Astrophysics Data System (ADS)

Ma, Ranran; Chen, Zhiwei; Wang, Suna; Yao, Qingxia; Li, Yunwu; Lu, Jing; Li, Dacheng; Dou, Jianmin

2017-08-01

Two helical Eu(III) metal-organic frameworks, namely, {[Eu(L)(DMF)(H2O)]·0.5DMF}n (1) and [Eu(L)(DEF)(H2O)]n (2) (H3L=3,5-bis(2-carboxylphenoxy)benzoic acid, DMF=N,N-dimethylformamide, DEF=N,N-diethylformamide), have been solvothermally synthesized in different solvents, respectively. Both complexes possess helical structures through the connectivity of Eu atoms and phenolic-oxygen containing branches of the flexible multicarboxylate ligand. Based on different helices, these two complexes exhibited hexagonal and tetragonal channels, respectively. Both complexes possess (3,6)-connected (4.62)2(42.610.83) topology but with different long Schlafli symbol. The solvent plays an important role in the formation of the final frameworks. Both complexes can sensitively and selectively detect nitrobenzene and Cu2+ ions.

Microbial degradation of complex carbohydrates in the gut.

PubMed

Flint, Harry J; Scott, Karen P; Duncan, Sylvia H; Louis, Petra; Forano, Evelyne

2012-01-01

Bacteria that colonize the mammalian intestine collectively possess a far larger repertoire of degradative enzymes and metabolic capabilities than their hosts. Microbial fermentation of complex non-digestible dietary carbohydrates and host-derived glycans in the human intestine has important consequences for health. Certain dominant species, notably among the Bacteroidetes, are known to possess very large numbers of genes that encode carbohydrate active enzymes and can switch readily between different energy sources in the gut depending on availability. Nevertheless, more nutritionally specialized bacteria appear to play critical roles in the community by initiating the degradation of complex substrates such as plant cell walls, starch particles and mucin. Examples are emerging from the Firmicutes, Actinobacteria and Verrucomicrobium phyla, but more information is needed on these little studied groups. The impact of dietary carbohydrates, including prebiotics, on human health requires understanding of the complex relationship between diet composition, the gut microbiota and metabolic outputs.

14N NQR study of hydrogen bonded complexes of 1,4 diazabicyclo [2,2,2] octane (ted) with phenols and thiourea

NASA Astrophysics Data System (ADS)

Murgich, Juan; Magaly, Santana R.; Diaz, Olga E.

The 14N NQR spectra of H bonded complexes of 1,4 diazabicyclo [2,2,2] octane, also known as triethylenediamine (TED), with phenol (1:2), p-chlorophenol (1:2), p-nitrophenol (1:2), hydroquinone (1:1), resorcinol (1:1) and thiourea (1:2) were observed at 77 K. The 14N frequency shifts produced by the H bonds in the TED complexes were approximately two times larger than those found for similar complexes of Hexamethylenetetramine (HMT). Such change was explained by the effect on the remaining N atoms of the increase in the number of -CH 2- groups and the decrease in N atoms in passing from HMT to TED. From the above results it seems that the inductive effect plays an important role in the formation of H bonds in tertiary amines like HMT and TED.

The emerging role of native mass spectrometry in characterizing the structure and dynamics of macromolecular complexes

PubMed Central

Boeri Erba, Elisabetta; Petosa, Carlo

2015-01-01

Mass spectrometry (MS) is a powerful tool for determining the mass of biomolecules with high accuracy and sensitivity. MS performed under so-called “native conditions” (native MS) can be used to determine the mass of biomolecules that associate noncovalently. Here we review the application of native MS to the study of protein−ligand interactions and its emerging role in elucidating the structure of macromolecular assemblies, including soluble and membrane protein complexes. Moreover, we discuss strategies aimed at determining the stoichiometry and topology of subunits by inducing partial dissociation of the holo-complex. We also survey recent developments in "native top-down MS", an approach based on Fourier Transform MS, whereby covalent bonds are broken without disrupting non-covalent interactions. Given recent progress, native MS is anticipated to play an increasingly important role for researchers interested in the structure of macromolecular complexes. PMID:25676284

Identifying hub stations and important lines of bus networks: A case study in Xiamen, China

NASA Astrophysics Data System (ADS)

Zhang, Hui; Zhuge, Chengxiang; Yu, Xiaohua

2018-07-01

Hub stations and important lines play key roles in transfers between stations. In this paper, a node failure model is proposed to identify hub stations. In the model, we introduce two new indicators called neighborhood degree ratio and transfer index to evaluate the importance of stations, which consider neighborhood stations' degree of station and the initial transfer times between stations. Moreover, line accessibility is developed to measure the importance of lines in the bus network. Xiamen bus network in 2016 is utilized to test the model. The results show that the two introduced indicators are more effective to identify hub stations compared with traditional complex network indicators such as degree, clustering coefficient and betweenness.

Interaction of Social and Play Behaviors in Preschoolers With and Without Pervasive Developmental Disorder

ERIC Educational Resources Information Center

Pierce-Jordan, Sandra; Lifter, Karin

2005-01-01

This study investigated the relationship between the social and play behaviors of young children with pervasive developmental disorder (PDD) and without PDD. Videotaped observations of 21 preschool children (12 with PDD and 9 without PDD) were examined independently for (a) social complexity and (b) play complexity that was assessed on an…

TSLP: A Key Regulator of Asthma Pathogenesis.

PubMed

West, Erin E; Kashyap, Mohit; Leonard, Warren J

2012-12-01

Asthma is a complex disorder of the airways that is characterized by T helper type 2 (Th2) inflammation. The pleiotrophic cytokine TSLP has emerged as an important player involved in orchestrating the inflammation seen in asthma and other atopic diseases. Early research elucidated the role of TSLP on CD4 + T cells, and recent work has revealed the impact of TSLP on multiple cell types. Furthermore, TSLP plays an important role in the sequential progression of atopic dermatitis to asthma, clarifying the key role of TSLP in the pathogenesis of asthma, a finding with therapeutic implications.

Impact of whole grains on the gut microbiota: the next frontier for oats?

PubMed

Rose, Devin J

2014-10-01

The gut microbiota plays important roles in proper gut function and can contribute to or help prevent disease. Whole grains, including oats, constitute important sources of nutrients for the gut microbiota and contribute to a healthy gut microbiome. In particular, whole grains provide NSP and resistant starch, unsaturated TAG and complex lipids, and phenolics. The composition of these constituents is unique in oats compared with other whole grains. Therefore, oats may contribute distinctive effects on gut health relative to other grains. Studies designed to determine these effects may uncover new human-health benefits of oat consumption.

The Mediator Complex Subunit PFT1 Is a Key Regulator of Jasmonate-Dependent Defense in Arabidopsis[C][W

PubMed Central

Kidd, Brendan N.; Edgar, Cameron I.; Kumar, Krish K.; Aitken, Elizabeth A.; Schenk, Peer M.; Manners, John M.; Kazan, Kemal

2009-01-01

Jasmonate signaling plays an important role in both plant defense and development. Here, we have identified a subunit of the Mediator complex as a regulator of the jasmonate signaling pathway in Arabidopsis thaliana. The Mediator complex is a conserved multiprotein complex that acts as a universal adaptor between transcription factors and the RNA polymerase II transcriptional machinery. We report that the PHYTOCHROME AND FLOWERING TIME1 (PFT1) gene, which encodes the MEDIATOR25 subunit of Mediator, is required for jasmonate-dependent defense gene expression and resistance to leaf-infecting necrotrophic fungal pathogens. Conversely, PFT1 appears to confer susceptibility to Fusarium oxysporum, a root-infecting hemibiotrophic fungal pathogen known to hijack jasmonate responses for disease development. Consistent with this, jasmonate gene expression was suppressed in the pft1 mutant during infection with F. oxysporum. In addition, a wheat (Triticum aestivum) homolog of PFT1 complemented the defense and the developmental phenotypes of the pft1 mutant, suggesting that the jasmonate signaling functions of PFT1 may be conserved in higher plants. Overall, our results identify an important control point in the regulation of the jasmonate signaling pathway within the transcriptional machinery. PMID:19671879

Cooperation of TOM and TIM23 complexes during translocation of proteins into mitochondria.

PubMed

Waegemann, Karin; Popov-Čeleketić, Dušan; Neupert, Walter; Azem, Abdussalam; Mokranjac, Dejana

2015-03-13

Translocation of the majority of mitochondrial proteins from the cytosol into mitochondria requires the cooperation of TOM and TIM23 complexes in the outer and inner mitochondrial membranes. The molecular mechanisms underlying this cooperation remain largely unknown. Here, we present biochemical and genetic evidence that at least two contacts from the side of the TIM23 complex play an important role in TOM-TIM23 cooperation in vivo. Tim50, likely through its very C-terminal segment, interacts with Tom22. This interaction is stimulated by translocating proteins and is independent of any other TOM-TIM23 contact known so far. Furthermore, the exposure of Tim23 on the mitochondrial surface depends not only on its interaction with Tim50 but also on the dynamics of the TOM complex. Destabilization of the individual contacts reduces the efficiency of import of proteins into mitochondria and destabilization of both contacts simultaneously is not tolerated by yeast cells. We conclude that an intricate and coordinated network of protein-protein interactions involving primarily Tim50 and also Tim23 is required for efficient translocation of proteins across both mitochondrial membranes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Absorption spectroscopic studies of Np(IV) complexes

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

Reed, D. T.

2004-01-01

The complexation of neptunium (IV) with selected inorganic and organic ligands was studied as part of an investigation to establish key subsurface interactions between neptunium and biological systems. The prevalence of reducing environments in most subsurface migation scenarios, which are in many cases induced by biological activity, has increased the role and importance of Np(IV) as a key subsurface neptunium oxidation state. The biodegradation of larger organics that often coexist with actinides in the subsurface leads to the formation of many organic acids as transient products that, by complexation, play a key role in defining the fate and speciation ofmore » neptunium in biologically active systems. These often compete with inorganic complexes e.g. hydrolysis and phosphate. Herein we report the results of a series of complexation studies based on new band formation of the characteristic 960 nm band for Np(IV). Formation constants for Np(IV) complexes with phosphate, hydrolysis, succinate, acetohydroxamic acid, and acetate were determined. These results show the 960 nm absorption band to be very amenable to these types of complexation studies.« less

On Chaotic and Hyperchaotic Complex Nonlinear Dynamical Systems

NASA Astrophysics Data System (ADS)

Mahmoud, Gamal M.

Dynamical systems described by real and complex variables are currently one of the most popular areas of scientific research. These systems play an important role in several fields of physics, engineering, and computer sciences, for example, laser systems, control (or chaos suppression), secure communications, and information science. Dynamical basic properties, chaos (hyperchaos) synchronization, chaos control, and generating hyperchaotic behavior of these systems are briefly summarized. The main advantage of introducing complex variables is the reduction of phase space dimensions by a half. They are also used to describe and simulate the physics of detuned laser and thermal convection of liquid flows, where the electric field and the atomic polarization amplitudes are both complex. Clearly, if the variables of the system are complex the equations involve twice as many variables and control parameters, thus making it that much harder for a hostile agent to intercept and decipher the coded message. Chaotic and hyperchaotic complex systems are stated as examples. Finally there are many open problems in the study of chaotic and hyperchaotic complex nonlinear dynamical systems, which need further investigations. Some of these open problems are given.

[The art of touch. Elisabeth Caland and the physio-aesthetics of piano playing].

PubMed

Herrgott, Gerhard

2008-06-01

The issue of how it is possible to play the piano without striking it was raised by Chopin: one must 'caresser' and not 'frapper' the piano. In her teachings on the art of piano playing, Elisabeth Caland (1862-1929) attempts to articulate a scientifically grounded solution to this complex (kin-)aesthetic problem. The solution turns on her intuitively discovered 'lowering of the shoulderblades' which was documented in 1904, through X-rays, by the Berlin physiologist René du Bois-Reymond, and recorded as a way of coordinating movement which had been unknown to physiology up to that time. Caland's physio-aesthetic of piano playing, which she worked out on the basis of du Bois-Reymond's observations, turns on the ideal of 'floating sound' put forward by her teacher Ludwig Deppe, and on Ferruccio Busoni's technique of piano playing. Her method makes essential use of what Feldenkrais would later call the 'sixth sense' (i.e. proprioceptive perception); in fact, it represents the first modern kinaesthetically based conception of piano playing. Caland's doctrine of touch was ahead of its time and it virtually disappeared from discussions of piano technique after 1930. But it has become accessible again through reprints of her most important writings: Deppe's doctrine of piano playing (1897), Sources of power in piano playing (1904), and Artistic piano playing (1910).

PDZ-containing proteins: alternative splicing as a source of functional diversity.

PubMed

Sierralta, Jimena; Mendoza, Carolina

2004-12-01

Scaffold proteins allow specific protein complexes to be assembled in particular regions of the cell at which they organize subcellular structures and signal transduction complexes. This characteristic is especially important for neurons, which are highly polarized cells. Among the domains contained by scaffold proteins, the PSD-95, Discs-large, ZO-1 (PDZ) domains are of particular relevance in signal transduction processes and maintenance of neuronal and epithelial polarity. These domains are specialized in the binding of the carboxyl termini of proteins allowing membrane proteins to be localized by the anchoring to the cytoskeleton mediated by PDZ-containing scaffold proteins. In vivo studies carried out in Drosophila have taught that the role of many scaffold proteins is not limited to a single process; thus, in many cases the same genes are expressed in different tissues and participate in apparently very diverse processes. In addition to the differential expression of interactors of scaffold proteins, the expression of variants of these molecular scaffolds as the result of the alternative processing of the genes that encode them is proving to be a very important source of variability and complexity on a main theme. Alternative splicing in the nervous system is well documented, where specific isoforms play roles in neurotransmission, ion channel function, neuronal cell recognition, and are developmentally regulated making it a major mechanism of functional diversity. Here we review the current state of knowledge about the diversity and the known function of PDZ-containing proteins in Drosophila with emphasis in the role played by alternatively processed forms in the diversity of functions attributed to this family of proteins.

The plant Polycomb repressive complex 1 (PRC1) existed in the ancestor of seed plants and has a complex duplication history.

PubMed

Berke, Lidija; Snel, Berend

2015-03-13

Polycomb repressive complex 1 (PRC1) is an essential protein complex for plant development. It catalyzes ubiquitination of histone H2A that is an important part of the transcription repression machinery. Absence of PRC1 subunits in Arabidopsis thaliana plants causes severe developmental defects. Many aspects of the plant PRC1 are elusive, including its origin and phylogenetic distribution. We established the evolutionary history of the plant PRC1 subunits (LHP1, Ring1a-b, Bmi1a-c, EMF1, and VRN1), enabled by sensitive phylogenetic methods and newly sequenced plant genomes from previously unsampled taxonomic groups. We showed that all PRC1 core subunits exist in gymnosperms, earlier than previously thought, and that VRN1 is a recent addition, found exclusively in eudicots. The retention of individual subunits in chlorophytes, mosses, lycophytes and monilophytes indicates that they can moonlight as part of other complexes or processes. Moreover, we showed that most PRC1 subunits underwent a complex, duplication-rich history that differs significantly between Brassicaceae and other eudicots. PRC1 existed in the last common ancestor of seed plants where it likely played an important regulatory role, aiding their radiation. The presence of LHP1, Ring1 and Bmi1 in mosses, lycophytes and monilophytes also suggests the presence of a primitive yet functional PRC1.

Dynamics of water around the complex structures formed between the KH domains of far upstream element binding protein and single-stranded DNA molecules

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

Chakraborty, Kaushik; Bandyopadhyay, Sanjoy, E-mail: sanjoy@chem.iitkgp.ernet.in

2015-07-28

Single-stranded DNA (ss-DNA) binding proteins specifically bind to the single-stranded regions of the DNA and protect it from premature annealing, thereby stabilizing the DNA structure. We have carried out atomistic molecular dynamics simulations of the aqueous solutions of two DNA binding K homology (KH) domains (KH3 and KH4) of the far upstream element binding protein complexed with two short ss-DNA segments. Attempts have been made to explore the influence of the formation of such complex structures on the microscopic dynamics and hydrogen bond properties of the interfacial water molecules. It is found that the water molecules involved in bridging themore » ss-DNA segments and the protein domains form a highly constrained thin layer with extremely retarded mobility. These water molecules play important roles in freezing the conformational oscillations of the ss-DNA oligomers and thereby forming rigid complex structures. Further, it is demonstrated that the effect of complexation on the slow long-time relaxations of hydrogen bonds at the interface is correlated with hindered motions of the surrounding water molecules. Importantly, it is observed that the highly restricted motions of the water molecules bridging the protein and the DNA components in the complexed forms originate from more frequent hydrogen bond reformations.« less

SUN1 Regulates HIV-1 Nuclear Import in a Manner Dependent on the Interaction between the Viral Capsid and Cellular Cyclophilin A.

PubMed

Luo, Xinlong; Yang, Wei; Gao, Guangxia

2018-07-01

Human immunodeficiency virus type 1 (HIV-1) can infect nondividing cells via passing through the nuclear pore complex. The nuclear membrane-imbedded protein SUN2 was recently reported to be involved in the nuclear import of HIV-1. Whether SUN1, which shares many functional similarities with SUN2, is involved in this process remained to be explored. Here we report that overexpression of SUN1 specifically inhibited infection by HIV-1 but not that by simian immunodeficiency virus (SIV) or murine leukemia virus (MLV). Overexpression of SUN1 did not affect reverse transcription but led to reduced accumulation of the 2-long-terminal-repeat (2-LTR) circular DNA and integrated viral DNA, suggesting a block in the process of nuclear import. HIV-1 CA was mapped as a determinant for viral sensitivity to SUN1. Treatment of SUN1-expressing cells with cyclosporine (CsA) significantly reduced the sensitivity of the virus to SUN1, and an HIV-1 mutant containing CA-G89A, which does not interact with cyclophilin A (CypA), was resistant to SUN1 overexpression. Downregulation of endogenous SUN1 inhibited the nuclear entry of the wild-type virus but not that of the G89A mutant. These results indicate that SUN1 participates in the HIV-1 nuclear entry process in a manner dependent on the interaction of CA with CypA. IMPORTANCE HIV-1 infects both dividing and nondividing cells. The viral preintegration complex (PIC) can enter the nucleus through the nuclear pore complex. It has been well known that the viral protein CA plays an important role in determining the pathways by which the PIC enters the nucleus. In addition, the interaction between CA and the cellular protein CypA has been reported to be important in the selection of nuclear entry pathways, though the underlying mechanisms are not very clear. Here we show that both SUN1 overexpression and downregulation inhibited HIV-1 nuclear entry. CA played an important role in determining the sensitivity of the virus to SUN1: the regulatory activity of SUN1 toward HIV-1 relied on the interaction between CA and CypA. These results help to explain how SUN1 is involved in the HIV-1 nuclear entry process. Copyright © 2018 American Society for Microbiology.

Engineering Ecosystems and Synthetic Ecologies#

PubMed Central

Mee, Michael T; Wang, Harris H

2012-01-01

Microbial ecosystems play an important role in nature. Engineering these systems for industrial, medical, or biotechnological purposes are important pursuits for synthetic biologists and biological engineers moving forward. Here, we provide a review of recent progress in engineering natural and synthetic microbial ecosystems. We highlight important forward engineering design principles, theoretical and quantitative models, new experimental and manipulation tools, and possible applications of microbial ecosystem engineering. We argue that simply engineering individual microbes will lead to fragile homogenous populations that are difficult to sustain, especially in highly heterogeneous and unpredictable environments. Instead, engineered microbial ecosystems are likely to be more robust and able to achieve complex tasks at the spatial and temporal resolution needed for truly programmable biology. PMID:22722235

Sleep and Cognition

PubMed Central

Deak, Maryann C.; Stickgold, Robert

2018-01-01

Sleep is a complex physiologic state, the importance of which has long been recognized. Lack of sleep is detrimental to humans and animals. Over the past decade, an important link between sleep and cognitive processing has been established. Sleep plays an important role in consolidation of different types of memory and contributes to insightful, inferential thinking. While the mechanism by which memories are processed in sleep remains unknown, several experimental models have been proposed. This article explores the link between sleep and cognition by reviewing (1) the effects of sleep deprivation on cognition, (2) the influence of sleep on consolidation of declarative and non-declarative memory, and 3) some proposed models of how sleep facilitates memory consolidation in sleep. PMID:26271496

Structure and reactivity of ferrihydrite-soil organic carbon-calcium ternary complexes

NASA Astrophysics Data System (ADS)

Yang, Y.; Adhikari, D.; Sowers, T.; Stuckey, J.; Poulson, S.; Sparks, D. L.

2017-12-01

Complete understanding about the interactions between soil organic carbon (SOC) and minerals is important for predicting the stability of SOC and its response to climate change. Recent studies have shown the importance of calcium (Ca)-bearing minerals and iron (Fe) oxide in associating with and stabilizing SOC. In this study, we have investigated the formation and reactivity of ferrihydrite-SOC-Ca ternary complexes. During the co-precipitation of ferrihydrite with SOC in the presence of Ca2+, 60% of SOC can be co-precipitated with ferrihydrite at a C/Fe (molar ratio) of up to 10, whereas the Ca/Fe ratio was saturated at 0.2. Increasing amount of Ca2+ did not affect the co-precipitation of SOC with ferrihydrite or the lability of ferrihydrite-bound SOC. In addition, microbial reduction of ferrihydrite and reductive release of ferrihydrite-bound SOC were not influenced by the presence of Ca, but the pathway for Fe mineral transformation during the reduction was affected by Ca. In the meantime, Fe reduction selectively released carboxylic-enriched SOC. As a comparison, the presence of SOC increased the incorporation of Ca into the structure of ferrihydrite. Our results indicate the formation of ferrihydrite-SOC-Ca complexes, with organic carbon bridging the ferrihydrite and Ca. Such ternary complexes potentially play an important role in regulating the interactions between SOC and mineral phases in soil.

Two-Photon-Active Organotin(IV) Complexes for Antibacterial Function and Superresolution Bacteria Imaging.

PubMed

Hu, Lei; Wang, Hui; Xia, Tingting; Fang, Bin; Shen, Yu; Zhang, Qiong; Tian, Xiaohe; Zhou, Hongping; Wu, Jieying; Tian, Yupeng

2018-06-04

Antibacterial agents with two-photon absorption are expected to play a significant role in biomedical science. Herein, two novel organotin complexes, HLSn1 and HLSn2, based on coumarin were designed, synthesized, and systematically investigated. It was found that these complexes possessed suitable two-photon-active cross sections in the near-infrared region. Moreover, complex HLSn1 could efficiently inhibit the growth of Gram-negative Escherichia coli and Gram-positive Bacillus subtilis, especially the latter with a minimum inhibitory concentration (MIC; 90%) of 2 ± 0.14 μg mL -1 , which is lower than that of Kanamycin (Kana, 8 ± 0.42 μg mL -1 ). Importantly, two-photon imaging and superresolution development of bacterial stain revealed that complex HLSn1 can react with bacterial membranes, producing reactive oxygen species (ROS) and leading to cell death. These outcomes provide promising applications in the superresolution bacteria imaging, diagnostics, and treatment of bacterial infectious.

Encapsulation of labetalol, pseudoephedrine in β-cyclodextrin cavity: spectral and molecular modeling studies.

PubMed

Prabhu, A Antony Muthu; Rajendiran, N

2012-11-01

The absorption and fluorescence spectra of labetalol and pseudoephedrine have been studied in different polarities of solvents and β-cyclodextrin (β-CD). The inclusion complexation with β-CD is investigated by UV-visible, steady state and time resolved fluorescence spectra and PM3 method. In protic solvents, the normal emission originates from a locally excited state and the longer wavelength emission is due to intramolecular charge transfer (TICT). Labetalol forms a 1:2 complex and pseudoephedrine forms 1:1 complex with β-CD. Nanosecond time-resolved studies indicated that both molecules show triexponential decay. Thermodynamic parameters (ΔG, ΔH, ΔS) and HOMO, LUMO orbital investigations confirm the stability of the inclusion complex. The geometry of the most stable complex shows that the aromatic ring is deeply self included inside the β-CD cavity and intermolecular hydrogen bonds were established between host and guest molecules. This suggests that hydrophobic effect and hydrogen bond play an important role in the inclusion process.

WAVE2 forms a complex with PKA and is involved in PKA enhancement of membrane protrusions.

PubMed

Yamashita, Hiroshi; Ueda, Kazumitsu; Kioka, Noriyuki

2011-02-04

PKA contributes to many physiological processes, including glucose homeostasis and cell migration. The substrate specificity of PKA is low compared with other kinases; thus, complex formation with A-kinase-anchoring proteins is important for the localization of PKA in specific subcellular regions and the phosphorylation of specific substrates. Here, we show that PKA forms a complex with WAVE2 (Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2) in MDA-MB-231 breast cancer cells and mouse brain extracts. Two separate regions of WAVE2 are involved in WAVE2-PKA complex formation. This complex localizes to the leading edge of MDA-MB-231 cells. PKA activation results in enlargement of the membrane protrusion. WAVE2 depletion impairs PKA localization at membrane protrusions and the enlargement of membrane protrusion induced by PKA activation. Together, these results suggest that WAVE2 works as an A-kinase-anchoring protein that recruits PKA at membrane protrusions and plays a role in the enlargement of membrane protrusions induced by PKA activation.

The neural processing of musical instrument size information in the brain investigated by magnetoencephalography

NASA Astrophysics Data System (ADS)

Rupp, Andre; van Dinther, Ralph; Patterson, Roy D.

2005-04-01

The specific cortical representation of size was investigated by recording auditory evoked fields (AEFs) elicited by changes of instrument size and pitch. In Experiment 1, a French horn and one scaled to double the size played a three note melody around F3 or its octave, F4. Many copies of these four melodies were played in random order and the AEF was measured continuously. A similar procedure was applied to saxophone sounds in a separate run. In Experiment 2, the size and type of instrument (French horn and saxophone) were varied without changing the octave. AEFs were recorded in five subjects using magnetoencephalography and evaluated by spatio-temporal source analysis with one equivalent dipole in each hemisphere. The morphology of the source waveforms revealed that each note within the melody elicits a well-defined P1-N1-P2 AEF-complex with adaptation for the 2nd and 3rd note. At the transition of size, pitch, or both, a larger AEF-complex was evoked. However, size changes elicited a stronger N1 than pitch changes. Furthermore, this size-related N1 enhancement was larger for French horn than saxophone. The results indicate that the N1 plays an important role in the specific representation of instrument size.

Recovery of Herbaspirillum Species from Persons with Cystic Fibrosis▿

PubMed Central

Spilker, Theodore; Uluer, Ahmet Z.; Marty, Francisco M.; Yeh, Wendy W.; Levison, Julie H.; Vandamme, Peter; LiPuma, John J.

2008-01-01

Herbaspirillum species are not known to be human pathogens. We report on the identification of Herbaspirillum from cultures from 28 persons with cystic fibrosis (CF). Most isolates were initially identified as members of the Burkholderia cepacia complex. Although the role that these species play in lung disease in persons with CF is not known, their differentiation from other species is important and has serious implications for clinical care and patient well-being. PMID:18524958

Triton X-100 as an effective surfactant for the isolation and purification of photosystem I from Arthrospira platensis.

PubMed

Yu, Daoyong; Huang, Guihong; Xu, Fengxi; Wang, Mengfei; Liu, Shuang; Huang, Fang

2014-06-01

Surfactants play important roles in the preparation, structural, and functional research of membrane proteins, and solubilizing and isolating membrane protein, while keeping their structural integrity and activity intact is complicated. The commercial n-Dodecyl-β-D-maltoside (DDM) and Triton X-100 (TX) were used as solubilizers to extract and purify trimeric photosystem I (PSI) complex, an important photosynthetic membrane protein complex attracting broad interests. With an optimized procedure, TX can be used as an effective surfactant to isolate and purify PSI, as a replace of the much more expensive DDM. A mechanism was proposed to interpret the solubilization process at surfactant concentrations lower than the critical solubilization concentration. PSI-TX and PSI-DDM had identical polypeptide bands, pigment compositions, oxygen consumption, and photocurrent activities. This provides an alternative procedure and paves a way for economical and large-scale trimeric PSI preparation.

Reference Materials: Significance, General Requirements, and Demand.

PubMed

Kiełbasa, Anna; Gadzała-Kopciuch, Renata; Buszewski, Bogusław

2016-05-03

Reference materials play an important part in the quality control of measurements. Rapid development of such new scientific disciplines as proteomics, metabolomics, and genomics also necessitates development of new reference materials. This is a great challenge due to the complexity of the production of new reference materials and difficulties associated with achieving their homogeneity and stability. CRMs of tissue are of particular importance. They can be counted among the matrices that are most complex and time consuming in preparation. Tissue is the place of transformation and accumulation of many substances (e.g., metabolites, which are intermediate or end products resulting from metabolic processes). Trace amounts of many substances in tissues must be determined with adequate precision and accuracy. To meet the needs stemming from research and from problems and challenges faced by chemists, analysts, and toxicologists, the number of certified reference materials should be continuously increased.

Self-assembly kinetics of DNA functionalised liposomes

NASA Astrophysics Data System (ADS)

Mognetti, B. M.; Bachmann, S. J.; Kotar, J.; Parolini, L.; Petitzon, M.; Cicuta, P.; di Michele, L.

DNA has been largely used to program state-dependent interactions between functionalised Brownian units resulting in responsive systems featuring complex phase behaviours. In this talk I will show how DNA can also be used to control aggregation kinetics in systems of liposomes functionalised by three types of linkers that can simultaneously bind. In doing so, I will present a general coarse-graining strategy that allows calculating the adhesion free energy between pairs of compliant units functionalised by mobile binders. I will highlight the important role played by bilayer deformability and will calculate the free energy contribution due to the presence of complexes made by more than two binders. Finally we will demonstrate the importance of explicitly accounting for the kinetics underlying ligand-receptor reactions when studying large-scale self-assembly. We acknowledge support from ULB, the Oppenheimer Fund, and the EPSRC Programme Grant CAPITALS No. EP/J017566/1.

Information flow in the pharmaceutical supply chain

PubMed Central

Yousefi, Nazila; Alibabaei, Ahmad

2015-01-01

Managing the supply chain plays an important role in creating competitive advantages for companies. Adequate information flow in supply chain is one of the most important issues in SCM. Therefore, using certain Information Systems can have a significant role in managing and integrating data and information within the supply chain. Pharmaceutical supply chain is more complex than many other supply chains, in the sense that it can affect social and political perspectives. On the other hand, managing the pharmaceutical supply chain is difficult because of its complexity and also government regulations in this field. Although, Iran has progressed a lot in pharmaceutical manufacturing, still there are many unsolved issues in managing the information flow in the pharmaceutical supply chain. In this study, we reviewed the benefits of using different levels of an integrated information system in the supply chain and the possible challenges ahead. PMID:26664401

Play Complexity and Toy Engagement in Preschoolers with Autism Spectrum Disorder: Do Girls and Boys Differ?

ERIC Educational Resources Information Center

Harrop, Clare; Green, Jonathan; Hudry, Kristelle

2017-01-01

While sex differences in play have been extensively observed in typical development, only a handful of studies have explored this phenomenon in depth with children with autism spectrum disorders. This study explored sex differences in play complexity and toy engagement within caregiver-child interaction samples for preschool-aged children (2-5…

Repair of Acute Superficial Deltoid Complex Avulsion During Ankle Fracture Fixation in National Football League Players.

PubMed

Hsu, Andrew R; Lareau, Craig R; Anderson, Robert B

2015-11-01

Infolding and retraction of an avulsed deltoid complex after ankle fracture can be a source of persistent increased medial clear space, malreduction, and postoperative pain and medial instability. The purpose of this descriptive case series was to analyze the preliminary outcomes of acute superficial deltoid complex avulsion repair during ankle fracture fixation in a cohort of National Football League (NFL) players. We found that there is often complete avulsion of the superficial deltoid complex off the proximal aspect of the medial malleolus during high-energy ankle fractures in athletes. Between 2004 and 2014, the cases of 14 NFL players who underwent ankle fracture fixation with open deltoid complex repair were reviewed. Patients with chronic deltoid ligament injuries or ankle fractures more than 2 months old were excluded. Average age for all patients was 25 years and body mass index 34.4. Player positions included 1 wide receiver, 1 tight end, 1 safety, 1 running back, 1 linebacker, and 9 offensive linemen. Average time from injury to surgery was 7.5 days. Surgical treatment for all patients consisted of ankle arthroscopy and debridement, followed by fibula fixation with plate and screws, syndesmotic fixation with suture-button devices, and open deltoid complex repair with suture anchors. Patient demographics were recorded with position played, time from injury to surgery, games played before and after surgery, ability to return to play, and postoperative complications. Return to play was defined as the ability to successfully participate in at least 1 full regular-season NFL game after surgery. All NFL players were able to return to running and cutting maneuvers by 6 months after surgery. There were no significant differences in playing experience before surgery versus after surgery. Average playing experience before surgery was 3.3 seasons, 39 games played, and 22 games started. Average playing experience after surgery was 1.6 seasons, 16 games played, and 15 games started. Return to play was 86% for all players. There were no intraoperative or postoperative complications noted, and no players had clinical evidence of medial pain or instability at final follow-up with radiographic maintenance of anatomic mortise alignment. Superficial deltoid complex avulsion during high-energy ankle fractures in athletes is a distinct injury pattern that should be recognized and may benefit from primary open repair. The majority of NFL players treated surgically for this injury pattern are able to return to play after surgery with no reported complications or persistent medial ankle pain or instability. Level IV, retrospective case series. © The Author(s) 2015.

Histone H3 Lysine 14 (H3K14) Acetylation Facilitates DNA Repair in a Positioned Nucleosome by Stabilizing the Binding of the Chromatin Remodeler RSC (Remodels Structure of Chromatin)*

PubMed Central

Duan, Ming-Rui; Smerdon, Michael J.

2014-01-01

Histone H3 acetylation is induced by UV damage in yeast and may play an important role in regulating the repair of UV photolesions in nucleosome-loaded genomic loci. However, it remains elusive how H3 acetylation facilitates repair. We generated a strongly positioned nucleosome containing homogeneously acetylated H3 at Lys-14 (H3K14ac) and investigated possible mechanisms by which H3K14 acetylation modulates repair. We show that H3K14ac does not alter nucleosome unfolding dynamics or enhance the repair of UV-induced cyclobutane pyrimidine dimers by UV photolyase. Importantly, however, nucleosomes with H3K14ac have a higher affinity for purified chromatin remodeling complex RSC (Remodels the Structure of Chromatin) and show greater cyclobutane pyrimidine dimer repair compared with unacetylated nucleosomes. Our study indicates that, by anchoring RSC, H3K14 acetylation plays an important role in the unfolding of strongly positioned nucleosomes during repair of UV damage. PMID:24515106

The Eosinophil in Infection.

PubMed

Ravin, Karen A; Loy, Michael

2016-04-01

First described by Paul Ehrlich in 1879, who noted its characteristic staining by acidophilic dyes, for many years, the eosinophil was considered to be an end-effector cell associated with helminth infections and a cause of tissue damage. Over the past 30 years, research has helped to elucidate the complexity of the eosinophil's function and establish its role in host defense and immunity. Eosinophils express an array of ligand receptors which play a role in cell growth, adhesion, chemotaxis, degranulation, and cell-to-cell interactions. They play a role in activation of complement via both classical and alternative pathways. Eosinophils synthesize, store and secrete cytokines, chemokines, and growth factors. They can process antigen, stimulate T cells, and promote humoral responses by interacting with B cells. Eosinophils can function as antigen presenting cells and can regulate processes associated with both T1 and T2 immunity. Although long known to play a role in defense against helminth organisms, the interactions of eosinophils with these parasites are now recognized to be much more complex. In addition, their interaction with other pathogens continues to be investigated. In this paper, we review the eosinophil's unique biology and structure, including its characteristic granules and the effects of its proteins, our developing understanding of its role in innate and adaptive immunity and importance in immunomodulation, and the part it plays in defense against parasitic, viral, fungal and bacterial infections. Rather than our worst enemy, the eosinophil may, in fact, be one of the most essential components in host defense and immunity.

Androgens and bone health.

PubMed

Hansen, K A; Tho, S P

1998-01-01

Osteoporosis is one of the most common metabolic bone diseases in the adult population and its prevalence will continue to rise as our population grows older. In both sexes, hypogonadism is associated with accelerated loss of bone and development of osteoporosis. Adrenal and gonadal androgen levels decline with advancing age in both sexes. Androgens act by either directly binding to androgen receptors, or by aromatization of androgens to estrogens and subsequently interacting with estrogen receptors. Both pathways are important for skeletal health. Direct androgen binding to an androgen receptor may play a more important role in early skeletal development and determination of sexual dimorphic traits. While bone remodeling, which is important in maintaining healthy bone through life, is primarily stimulated by estrogen, studies in the rat and human support the complex action of androgens and estrogens in bone modeling and remodeling, and hence the development and maintenance of healthy bone. In postmenopausal females, the addition of androgens to hormone replacement therapy results in significant additional improvement in bone mineral density compared to estrogen replacement alone. Accumulating evidence indicate that androgens play an important role in the health of bone and the potential benefit of adding these agents to hormone replacement regimens.

Sports Injuries about the Hip: What the Radiologist Should Know.

PubMed

Hegazi, Tarek M; Belair, Jeffrey A; McCarthy, Eoghan J; Roedl, Johannes B; Morrison, William B

2016-10-01

Injuries of the hip and surrounding structures represent a complex and commonly encountered scenario in athletes, with improper diagnosis serving as a cause of delayed return to play or progression to a more serious injury. As such, radiologists play an essential role in guiding management of athletic injuries. Familiarity with hip anatomy and the advantages and limitations of various imaging modalities is of paramount importance for accurate and timely diagnosis. Magnetic resonance (MR) imaging is often the modality of choice for evaluating many of the injuries discussed, although preliminary evaluation with conventional radiography and use of other imaging modalities such as ultrasonography (US), computed tomography, and bone scintigraphy may be supplementary or preferred in certain situations. Stress fractures, thigh splints, and posterior hip dislocations are important structural injuries to consider in the athlete, initially imaged with radiographs and often best diagnosed with MR imaging. Apophyseal injuries are particularly important to consider in young athletes and may be acute or related to chronic repetitive microtrauma. Femoroacetabular impingement has been implicated in development of labral tears and cartilage abnormalities. Tear of the ligamentum teres is now recognized as a potential cause of hip pain and instability, best evaluated with MR arthrography. Greater trochanteric pain syndrome encompasses a group of conditions leading to lateral hip pain, with US playing an increasingly important role for both evaluation and image-guided treatment. Muscle injuries and athletic pubalgia are common in athletes. Lastly, snapping hip syndrome and Morel-Lavallée lesions are two less common but nonetheless important considerations. © RSNA, 2016.

RNF8- and Ube2S-Dependent Ubiquitin Lysine 11-Linkage Modification in Response to DNA Damage.

PubMed

Paul, Atanu; Wang, Bin

2017-05-18

Ubiquitin modification of proteins plays pivotal roles in the cellular response to DNA damage. Given the complexity of ubiquitin conjugation due to the formation of poly-conjugates of different linkages, functional roles of linkage-specific ubiquitin modification at DNA damage sites are largely unclear. We identify that Lys11-linkage ubiquitin modification occurs at DNA damage sites in an ATM-dependent manner, and ubiquitin-modifying enzymes, including Ube2S E2-conjugating enzyme and RNF8 E3 ligase, are responsible for the assembly of Lys11-linkage conjugates on damaged chromatin, including histone H2A/H2AX. We show that RNF8- and Ube2S-dependent Lys11-linkage ubiquitin conjugation plays an important role in regulating DNA damage-induced transcriptional silencing, distinct from the role of Lys63-linkage ubiquitin in the recruitment of DNA damage repair proteins 53BP1 and BRCA1. Thus, our study highlights the importance of linkage-specific ubiquitination at DNA damage sites, and it reveals that Lys11-linkage ubiquitin modification plays a crucial role in the DNA damage response. Copyright © 2017 Elsevier Inc. All rights reserved.

Structure and reactivity of oxalate surface complexes on lepidocrocite derived from infrared spectroscopy, DFT-calculations, adsorption, dissolution and photochemical experiments

NASA Astrophysics Data System (ADS)

Borowski, Susan C.; Biswakarma, Jagannath; Kang, Kyounglim; Schenkeveld, Walter D. C.; Hering, Janet G.; Kubicki, James D.; Kraemer, Stephan M.; Hug, Stephan J.

2018-04-01

Oxalate, together with other ligands, plays an important role in the dissolution of iron(hdyr)oxides and the bio-availability of iron. The formation and properties of oxalate surface complexes on lepidocrocite were studied with a combination of infrared spectroscopy (IR), density functional theory (DFT) calculations, dissolution, and photochemical experiments. IR spectra measured as a function of time, concentration, and pH (50-200 μM oxalate, pH 3-7) showed that several surface complexes are formed at different rates and in different proportions. Measured spectra could be separated into three contributions described by Gaussian line shapes, with frequencies that agreed well with the theoretical frequencies of three different surface complexes: an outer-sphere complex (OS), an inner-sphere monodentate mononuclear complex (MM), and a bidentate mononuclear complex (BM) involving one O atom from each carboxylate group. At pH 6, OS was formed at the highest rate. The contribution of BM increased with decreasing pH. In dissolution experiments, lepidocrocite was dissolved at rates proportional to the surface concentration of BM, rather than to the total adsorbed concentration. Under UV-light (365 nm), BM was photolyzed at a higher rate than MM and OS. Although the comparison of measured spectra with calculated frequencies cannot exclude additional possible structures, the combined results allowed the assignment of three main structures with different reactivities consistent with experiments. The results illustrate the importance of the surface speciation of adsorbed ligands in dissolution and photochemical reactions.

Solve the Dilemma of Over-Simplification

NASA Astrophysics Data System (ADS)

Schmitt, Gerhard

Complexity science can help to understand the functioning and the interaction of the components of a city. In 1965, Christopher Alexander gave in his book A city is not a tree a description of the complex nature of urban organization. At this time, neither high-speed computers nor urban big data existed. Today, Luis Bettencourt et al. use complexity science to analyze data for countries, regions, or cities. The results can be used globally in other cities. Objectives of complexity science with regard to future cities are the observation and identification of tendencies and regularities in behavioral patterns, and to find correlations between them and spatial configurations. Complex urban systems cannot be understood in total yet. But research focuses on describing the system by finding some simple, preferably general and emerging patterns and rules that can be used for urban planning. It is important that the influencing factors are not just geo-spatial patterns but also consider variables which are important for the design quality. Complexity science is a way to solve the dilemma of oversimplification of insights from existing cities and their applications to new cities. An example: The effects of streets, public places and city structures on citizens and their behavior depend on how they are perceived. To describe this perception, it is not sufficient to consider only particular characteristics of the urban environment. Different aspects play a role and influence each other. Complexity science could take this fact into consideration and handle the non-linearity of the system...

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

Electrocatalytic Oxidation of Formate with Nickel Diphosphane Dipeptide Complexes. Effect of Ligands Modified with Amino Acids

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

Galan, Brandon R.; Reback, Matthew L.; Jain, Avijita

2013-09-03

A series of nickel bis-diphosphine complexes with dipeptides appended to the ligands were investigated for the catalytic oxidation of formate. Typical rates of ~7 s -1 were found, similar to the parent complex (~8 s -1), with amino acid size and positioning contributing very little to rate or operating potential. Hydroxyl functionalities did result in lower rates, which were recovered by protecting the hydroxyl group. The results suggest that the overall dielectric introduced by the dipeptides does not play an important role in catalysis, but free hydroxyl groups do influence activity suggesting contributions from intra- or intermolecular interactions. These observationsmore » are important in developing a fundamental understanding of the affect that an enzyme-like outer coordination sphere can have upon molecular catalysts. This work was funded by the US DOE Basic Energy Sciences, Chemical Sciences, Geoscience and Biosciences Division (BRG, AJ, AMA, WJS), the US DOE Basic Energy Sciences, Physical Bioscience program (MLR). Pacific Northwest National Laboratory is operated by Battelle for the U.S. Department of Energy.« less

Nano-structure of the laminin γ-1 short arm reveals an extended and curved multidomain assembly.

PubMed

Patel, Trushar R; Morris, Gordon A; Zwolanek, Daniela; Keene, Douglas R; Li, Jianhua; Harding, Stephen E; Koch, Manuel; Stetefeld, Jörg

2010-09-01

Laminins are multidomain glycoproteins that play important roles in development and maintenance of the extracellular matrix via their numerous interactions with other proteins. Several receptors for the laminin short arms revealed their importance in network formation and intercellular signaling. However, both the detailed structure of the laminin γ-1 short arm and its organization within the complexes is poorly understood due to the complexity of the molecule and the lack of a high-resolution structure. The presented data provide the first subatomic resolution structure for the laminin γ-1 short arm in solution. This was achieved using an integrated approach that combined a number of complementary biophysical techniques such as small angle X-ray scattering (SAXS), analytical ultracentrifugation, dynamic light scattering and electron microscopy. As a result of this study, we have obtained a significantly improved model for the laminin γ-1 short arm that represents a major step forward in molecular understanding of laminin-mediated complex formations. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

Harmonic template neurons in primate auditory cortex underlying complex sound processing

PubMed Central

Feng, Lei

2017-01-01

Harmonicity is a fundamental element of music, speech, and animal vocalizations. How the auditory system extracts harmonic structures embedded in complex sounds and uses them to form a coherent unitary entity is not fully understood. Despite the prevalence of sounds rich in harmonic structures in our everyday hearing environment, it has remained largely unknown what neural mechanisms are used by the primate auditory cortex to extract these biologically important acoustic structures. In this study, we discovered a unique class of harmonic template neurons in the core region of auditory cortex of a highly vocal New World primate, the common marmoset (Callithrix jacchus), across the entire hearing frequency range. Marmosets have a rich vocal repertoire and a similar hearing range to that of humans. Responses of these neurons show nonlinear facilitation to harmonic complex sounds over inharmonic sounds, selectivity for particular harmonic structures beyond two-tone combinations, and sensitivity to harmonic number and spectral regularity. Our findings suggest that the harmonic template neurons in auditory cortex may play an important role in processing sounds with harmonic structures, such as animal vocalizations, human speech, and music. PMID:28096341

Pen-2 is dispensable for endoproteolysis of presenilin 1, and nicastrin-Aph subcomplex is important for both γ-secretase assembly and substrate recruitment

PubMed Central

Mao, Guozhang; Cui, Mei-Zhen; Li, Tong; Jin, Yipeng; Xu, Xuemin

2012-01-01

γ-secretase is a protease complex with at least four components: presenilin, nicastrin (NCT), anterior pharynx-defective 1 (Aph-1), and presenilin enhancer 2 (Pen-2). In this study, using knockout cell lines and small interfering RNA technology, our data demonstrated that the disappeared presenilin 1 C-terminal fragment (PS1C) caused by knockdown of pen-2 or knockout of NCT or Aph-1 was recovered by the addition of proteasome inhibitors, indicating that Pen-2, as well as NCT and Aph-1α , is dispensable for presenilin endoproteolysis. Our data also demonstrate that the formation of the nicastrin-Aph-1 subcomplex plays not only an important role in γ-secretase complex assembly but also in recruiting substrate C-terminal fragment of amyloid precursor protein generated by β-cleavage (CTFβ). Ablating any one component resulted in the instability of other components of the γ-secretase complex, and the presence of all three of the other components is required for full maturation of NCT. PMID:22973949

Transition metal-chelating surfactant micelle templates for facile synthesis of mesoporous silica nanoparticles

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

Lee, Hye Sun; Department of Materials Science and Engineering, Yonsei University, Seoul 120-749; Kim, Won Hee

2012-01-15

Highly ordered mesoporous silica nanoparticles with tunable morphology and pore-size are prepared by the use of a transition metal-chelating surfactant micelle complex using Co{sup 2+}, Ni{sup 2+}, Cu{sup 2+}, and Zn{sup 2+} ions. These metal ions formed a metal-P123 micelle complex in an aqueous solution, while the metal ions are chelated to the hydrophilic domain such as the poly(ethylene oxide) group of a P123 surfactant. The different complexation abilities of the utilized transition metal ions play an important role in determining the formation of nano-sized ordered MSNs due to the different stabilization constant of the metal-P123 complex. Consequently, from amore » particle length of 1700 nm in the original mesoporous silica materials, the particle length of ordered MSNs through the metal-chelating P123 micelle templates can be reduced to a range of 180-800 nm. Furthermore, the variation of pore size shows a slight change from 8.8 to 6.6 nm. In particular, the Cu{sup 2+}-chelated MSNs show only decreased particle size to 180 nm. The stability constants for the metal-P123 complex are calculated on the basis of molar conductance measurements in order to elucidate the formation mechanism of MSNs by the metal-chelating P123 complex templates. In addition, solid-state {sup 29}Si, {sup 13}C-NMR and ICP-OES measurements are used for quantitative characterization reveal that the utilized metal ions affect only the formation of a metal-P123 complex in a micelle as a template. - Graphical abstract: Metal-chelating surfactant micelle templates support a simple and facile preparations of size-tunable ordered MSNs. Black-Small-Square Highlights: Black-Right-Pointing-Pointer Facile preparation of mesoporous silica nanoparticles (MSNs) was achieved by metal-chelating surfactant micelle complex using Co{sup 2+}, Ni{sup 2+}, Cu{sup 2+}, and Zn{sup 2+} ions. Black-Right-Pointing-Pointer Different complexation of metal ions plays an important role in determining the formation of nano-sized ordered MSNs. Black-Right-Pointing-Pointer Systematic characterization of the synthesized materials was achieved by solid-state {sup 29}Si and {sup 13}C-NMR techniques, BET, FT-IR, and XPS. Black-Right-Pointing-Pointer Stability constants for the metal-P123 complex are calculated on the basis of molar conductance measurements in order to elucidate the formation mechanism.« less

CCR4-Not Complex Subunit Not2 Plays Critical Roles in Vegetative Growth, Conidiation and Virulence in Watermelon Fusarium Wilt Pathogen Fusarium oxysporum f. sp. niveum

PubMed Central

Dai, Yi; Cao, Zhongye; Huang, Lihong; Liu, Shixia; Shen, Zhihui; Wang, Yuyan; Wang, Hui; Zhang, Huijuan; Li, Dayong; Song, Fengming

2016-01-01

CCR4-Not complex is a multifunctional regulator that plays important roles in multiple cellular processes in eukaryotes. In the present study, the biological function of FonNot2, a core subunit of the CCR4-Not complex, was explored in Fusarium oxysporum f. sp. niveum (Fon), the causal agent of watermelon wilt disease. FonNot2 was expressed at higher levels in conidia and germinating conidia and during infection in Fon-inoculated watermelon roots than in mycelia. Targeted disruption of FonNot2 resulted in retarded vegetative growth, reduced conidia production, abnormal conidial morphology, and reduced virulence on watermelon. Scanning electron microscopy observation of infection behaviors and qRT-PCR analysis of in planta fungal growth revealed that the ΔFonNot2 mutant was defective in the ability to penetrate watermelon roots and showed reduced fungal biomass in root and stem of the inoculated plants. Phenotypic and biochemical analyses indicated that the ΔFonNot2 mutant displayed hypersensitivity to cell wall perturbing agents (e.g., Congo Red and Calcofluor White) and oxidative stress (e.g., H2O2 and paraquat), decreased fusaric acid content, and reduced reactive oxygen species (ROS) production during spore germination. Our data demonstrate that FonNot2 plays critical roles in regulating vegetable growth, conidiogenesis and conidia morphology, and virulence on watermelon via modulating cell wall integrity, oxidative stress response, ROS production and FA biosynthesis through the regulation of transcription of genes involved in multiple pathways. PMID:27695445

Deficiency of the Survival of Motor Neuron Protein Impairs mRNA Localization and Local Translation in the Growth Cone of Motor Neurons.

PubMed

Fallini, Claudia; Donlin-Asp, Paul G; Rouanet, Jeremy P; Bassell, Gary J; Rossoll, Wilfried

2016-03-30

Spinal muscular atrophy (SMA) is a neurodegenerative disease primarily affecting spinal motor neurons. It is caused by reduced levels of the survival of motor neuron (SMN) protein, which plays an essential role in the biogenesis of spliceosomal small nuclear ribonucleoproteins in all tissues. The etiology of the specific defects in the motor circuitry in SMA is still unclear, but SMN has also been implicated in mediating the axonal localization of mRNA-protein complexes, which may contribute to the axonal degeneration observed in SMA. Here, we report that SMN deficiency severely disrupts local protein synthesis within neuronal growth cones. We also identify the cytoskeleton-associated growth-associated protein 43 (GAP43) mRNA as a new target of SMN and show that motor neurons from SMA mouse models have reduced levels ofGAP43mRNA and protein in axons and growth cones. Importantly, overexpression of two mRNA-binding proteins, HuD and IMP1, restoresGAP43mRNA and protein levels in growth cones and rescues axon outgrowth defects in SMA neurons. These findings demonstrate that SMN plays an important role in the localization and local translation of mRNAs with important axonal functions and suggest that disruption of this function may contribute to the axonal defects observed in SMA. The motor neuron disease spinal muscular atrophy (SMA) is caused by reduced levels of the survival of motor neuron (SMN) protein, which plays a key role in assembling RNA/protein complexes that are essential for mRNA splicing. It remains unclear whether defects in this well characterized housekeeping function cause the specific degeneration of spinal motor neurons observed in SMA. Here, we describe an additional role of SMN in regulating the axonal localization and local translation of the mRNA encoding growth-associated protein 43 (GAP43). This study supports a model whereby SMN deficiency impedes transport and local translation of mRNAs important for neurite outgrowth and stabilization, thus contributing to axon degeneration, muscle denervation, and motor neuron cell death in SMA. Copyright © 2016 the authors 0270-6474/16/363811-10$15.00/0.

a Statistical Dynamic Approach to Structural Evolution of Complex Capital Market Systems

NASA Astrophysics Data System (ADS)

Shao, Xiao; Chai, Li H.

As an important part of modern financial systems, capital market has played a crucial role on diverse social resource allocations and economical exchanges. Beyond traditional models and/or theories based on neoclassical economics, considering capital markets as typical complex open systems, this paper attempts to develop a new approach to overcome some shortcomings of the available researches. By defining the generalized entropy of capital market systems, a theoretical model and nonlinear dynamic equation on the operations of capital market are proposed from statistical dynamic perspectives. The US security market from 1995 to 2001 is then simulated and analyzed as a typical case. Some instructive results are discussed and summarized.

A study of H-alpha velocities in NGC 1499, NGC 7000, and IC 1318B/C

NASA Technical Reports Server (NTRS)

Fountain, W. F.; Gary, G. A.; Odell, C. R.

1983-01-01

Multiple slit echelle spectrograph observations of the H-alpha emission line are used to map the radial velocities of the California Nebula (NGC 1499), the North American Nebula complex (NGC 7000 and IC 5070), and IC 1318B/C. The California Nebula is singularly constant in velocity, considering its geometry. The North American Nebula complex reflects a very simple, classical dynamical picture. The expansion discovered earlier in IC 1318B/C is confirmed, detailed, and the model refined. The new data, along with that in earlier papers of this series, show that stellar wind acceleration and champagne flow mechanisms both play important roles in determining the evolution of H II regions.

ADP-ribosyl-N₃: A Versatile Precursor for Divergent Syntheses of ADP-ribosylated Compounds.

PubMed

Li, Lingjun; Li, Qianqian; Ding, Shengqiang; Xin, Pengyang; Zhang, Yuqin; Huang, Shenlong; Zhang, Guisheng

2017-08-14

Adenosine diphosphate-ribose (ADP-ribose) and its derivatives play important roles in a series of complex physiological procedures. The design and synthesis of artificial ADP-ribosylated compounds is an efficient way to develop valuable chemical biology tools and discover new drug candidates. However, the synthesis of ADP-ribosylated compounds is currently difficult due to structural complexity, easily broken pyrophosphate bond and high hydrophilicity. In this paper, ADP-ribosyl-N₃ was designed and synthesized for the first time. With ADP-ribosyl-N₃ as the key precursor, a divergent post-modification strategy was developed to prepare structurally diverse ADP-ribosylated compounds including novel nucleotides and peptides bearing ADP-ribosyl moieties.

Molecular Designs for Enhancement of Polarity in Ferroelectric Soft Materials

NASA Astrophysics Data System (ADS)

Ohtani, Ryo; Nakaya, Manabu; Ohmagari, Hitomi; Nakamura, Masaaki; Ohta, Kazuchika; Lindoy, Leonard F.; Hayami, Shinya

2015-11-01

The racemic oxovanadium(IV) salmmen complexes, [VO((rac)-(4-X-salmmen))] (X = C12C10C5 (1), C16 (2), and C18 (3); salmmen = N,N‧-monomethylenebis-salicylideneimine) with “banana shaped” molecular structures were synthesized, and their ferroelectric properties were investigated. These complexes exhibit well-defined hysteresis loops in their viscous phases, moreover, 1 also displays liquid crystal behaviour. We observed a synergetic effect influenced by three structural aspects; the methyl substituents on the ethylene backbone, the banana shaped structure and the square pyramidal metal cores all play an important role in generating the observed ferroelectricity, pointing the way to a useful strategy for the creation of advanced ferroelectric soft materials.

Mechanisms of SN2 reactions: insights from a nearside/farside analysis.

PubMed

Hennig, Carsten; Schmatz, Stefan

2015-10-28

A nearside/farside analysis of differential cross sections has been performed for the complex-forming SN2 reaction Cl(-) + CH3Br → ClCH3 + Br(-). It is shown that for low rotational quantum numbers a direct "nearside" reaction mechanism plays an important role and leads to anisotropic differential cross sections. For high rotational quantum numbers, indirect mechanisms via a long-lived intermediate complex are prevalent (independent of a nearside/farside configuration), leading to isotropic cross sections. Quantum mechanical interference can be significant at specific energies or angles. Averaging over energies and angles reveals that the nearside/farside decomposition in a semiclassical interpretation can reasonably account for the analysis of the reaction mechanism.

Block Play and Mathematics Learning in Preschool: The Effects of Building Complexity, Peer and Teacher Interactions in the Block Area, and Replica Play Materials

ERIC Educational Resources Information Center

Trawick-Smith, Jeffrey; Swaminathan, Sudha; Baton, Brooke; Danieluk, Courtney; Marsh, Samantha; Szarwacki, Monika

2017-01-01

Block play has been included in early childhood classrooms for over a century, yet few studies have examined its effects on learning. Several previous investigations indicate that the complexity of block building is associated with math ability, but these studies were often conducted in adult-guided, laboratory settings. In the present…

The role of turbulent fluxes in the atmospheric boundary layer above a debris-covered glacier in the Himalayas

NASA Astrophysics Data System (ADS)

Steiner, J. F.; Stigter, E.; Litt, M.; Shea, J.; Bierkens, M. F.; Immerzeel, W. W.

2017-12-01

Debris-covered glaciers play an important role in the water cycle in high altitude catchments in the Himalaya. The melt dynamics of these glaciers are complex as a result of the debris. A thin debris layer (up to a few cm) may act as a facilitator of melt, whereas a thick layer serves primarily as an insulator. The debris cover itself shows a strong diurnal variation in temperature and humidity resulting in a complex interaction with the atmospheric boundary layer (ABL). Energy balance models are a common way to quantify sub-debris melt, but the importance of turbulent fluxes in this energy balance have so far been poorly investigated. We hypothesize that they may play a substantial role during phases of wetting and drying. In this study, ABL characteristics and surface turbulent fluxes are measured using an automatic weather station including an eddy-correlation (EC) system on the debris-covered Lirung glacier in Nepal over a 10 day period in late 2016, during the transition period from monsoon to the drier post-monsoon. The measurements are combined with surface temperature measurements and thermal UAV flights covering the footprint area of the EC tower to quantify the surface fluxes over a larger area. Our results show that turbulent fluxes do play a substantial role in the energy balance of debris-covered glaciers, and need to be accounted for to accurately simulate glacier melt. The EC tower results are subsequently evaluated against a number of different bulk approaches to quantify sensible and latent heat fluxes and are evaluated against turbulence characteristics. If found accurate enough, these approaches require less advanced measurement set-ups and can be applied on a wider scale.

Some new traveling wave exact solutions of the (2+1)-dimensional Boiti-Leon-Pempinelli equations.

PubMed

Qi, Jian-ming; Zhang, Fu; Yuan, Wen-jun; Huang, Zi-feng

2014-01-01

We employ the complex method to obtain all meromorphic exact solutions of complex (2+1)-dimensional Boiti-Leon-Pempinelli equations (BLP system of equations). The idea introduced in this paper can be applied to other nonlinear evolution equations. Our results show that all rational and simply periodic traveling wave exact solutions of the equations (BLP) are solitary wave solutions, the complex method is simpler than other methods, and there exist some rational solutions ur,2 (z) and simply periodic solutions us,2-6(z) which are not only new but also not degenerated successively by the elliptic function solutions. We believe that this method should play an important role for finding exact solutions in the mathematical physics. For these new traveling wave solutions, we give some computer simulations to illustrate our main results.

Differential identity of Filopodia and Tunneling Nanotubes revealed by the opposite functions of actin regulatory complexes.

PubMed

Delage, Elise; Cervantes, Diégo Cordero; Pénard, Esthel; Schmitt, Christine; Syan, Sylvie; Disanza, Andrea; Scita, Giorgio; Zurzolo, Chiara

2016-12-23

Tunneling Nanotubes (TNTs) are actin enriched filopodia-like protrusions that play a pivotal role in long-range intercellular communication. Different pathogens use TNT-like structures as "freeways" to propagate across cells. TNTs are also implicated in cancer and neurodegenerative diseases, making them promising therapeutic targets. Understanding the mechanism of their formation, and their relation with filopodia is of fundamental importance to uncover their physiological function, particularly since filopodia, differently from TNTs, are not able to mediate transfer of cargo between distant cells. Here we studied different regulatory complexes of actin, which play a role in the formation of both these structures. We demonstrate that the filopodia-promoting CDC42/IRSp53/VASP network negatively regulates TNT formation and impairs TNT-mediated intercellular vesicle transfer. Conversely, elevation of Eps8, an actin regulatory protein that inhibits the extension of filopodia in neurons, increases TNT formation. Notably, Eps8-mediated TNT induction requires Eps8 bundling but not its capping activity. Thus, despite their structural similarities, filopodia and TNTs form through distinct molecular mechanisms. Our results further suggest that a switch in the molecular composition in common actin regulatory complexes is critical in driving the formation of either type of membrane protrusion.

Study of production and pyrolysis characteristics of sweet orange flavor-β-cyclodextrin inclusion complex.

PubMed

Zhu, Guangyong; Xiao, Zuobing; Zhou, Rujun; Zhu, Yalun

2014-05-25

Flavor plays an important role and has been widely used in foods. Encapsulation can prevent the loss of volatile aromatic ingredients, provide protection and enhance the stability of the flavor. Kinetic and thermodynamic parameters are helpful in understanding the mechanism of molecular recognition between hosts and guests. This work focused on the study of production of a sweet orange flavor-β-cyclodextrin (CD) inclusion complex, and investigated the combination of flavor and β-CD by thermogravimetric analysis. Pyrolysis characteristics, kinetic and thermodynamic parameters of the flavor-β-CD inclusion complex were determined. The results showed that the flavor-β-CD inclusion complexes can form large aggregates in water. During thermal degradation of blank β-CD and flavor-β-CD inclusion complex, three main stages can be distinguished. The thermogravimetric (TG) curve of blank β-CD shows a leveling-off from room temperature to 250°C, while the TG curve of flavor-β-CD inclusion complex is downward sloping in this temperature range. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dosage Compensation of the X Chromosome: A Complex Epigenetic Assignment Involving Chromatin Regulators and Long Noncoding RNAs.

PubMed

Samata, Maria; Akhtar, Asifa

2018-06-20

X chromosome regulation represents a prime example of an epigenetic phenomenon where coordinated regulation of a whole chromosome is required. In flies, this is achieved by transcriptional upregulation of X chromosomal genes in males to equalize the gene dosage differences in females. Chromatin-bound proteins and long noncoding RNAs (lncRNAs) constituting a ribonucleoprotein complex known as the male-specific lethal (MSL) complex or the dosage compensation complex mediate this process. MSL complex members decorate the male X chromosome, and their absence leads to male lethality. The male X chromosome is also enriched with histone H4 lysine 16 acetylation (H4K16ac), indicating that the chromatin compaction status of the X chromosome also plays an important role in transcriptional activation. How the X chromosome is specifically targeted and how dosage compensation is mechanistically achieved are central questions for the field. Here, we review recent advances, which reveal a complex interplay among lncRNAs, the chromatin landscape, transcription, and chromosome conformation that fine-tune X chromosome gene expression.

Keeping time: could quantum beating in microtubules be the basis for the neural synchrony related to consciousness?

PubMed

Craddock, Travis J A; Priel, Avner; Tuszynski, Jack A

2014-06-01

This paper discusses the possibility of quantum coherent oscillations playing a role in neuronal signaling. Consciousness correlates strongly with coherent neural oscillations, however the mechanisms by which neurons synchronize are not fully elucidated. Recent experimental evidence of quantum beats in light-harvesting complexes of plants (LHCII) and bacteria provided a stimulus for seeking similar effects in important structures found in animal cells, especially in neurons. We argue that microtubules (MTs), which play critical roles in all eukaryotic cells, possess structural and functional characteristics that are consistent with quantum coherent excitations in the aromatic groups of their tryptophan residues. Furthermore we outline the consequences of these findings on neuronal processes including the emergence of consciousness.

Living supramolecular polymerization achieved by collaborative assembly of platinum(II) complexes and block copolymers

PubMed Central

Zhang, Kaka; Yeung, Margaret Ching-Lam; Leung, Sammual Yu-Lut; Yam, Vivian Wing-Wah

2017-01-01

An important feature of biological systems to achieve complexity and precision is the involvement of multiple components where each component plays its own role and collaborates with other components. Mimicking this, we report living supramolecular polymerization achieved by collaborative assembly of two structurally dissimilar components, that is, platinum(II) complexes and poly(ethylene glycol)-b-poly(acrylic acid) (PEG-b-PAA). The PAA blocks neutralize the charges of the platinum(II) complexes, with the noncovalent metal–metal and π–π interactions directing the longitudinal growth of the platinum(II) complexes into 1D crystalline nanostructures, and the PEG blocks inhibiting the transverse growth of the platinum(II) complexes and providing the whole system with excellent solubility. The ends of the 1D crystalline nanostructures have been found to be active during the assembly and remain active after the assembly. One-dimensional segmented nanostructures with heterojunctions have been produced by sequential growth of two types of platinum(II) complexes. The PAA blocks act as adapters at the heterojunctions for lattice matching between chemically and crystallographically different platinum(II) complexes, achieving heterojunctions with a lattice mismatch as large as 21%. PMID:29078381

Reactivity Study of Unsymmetrical β-Diketiminato Copper(I) Complexes: Effect of the Chelating Ring.

PubMed

Chuang, Wan-Jung; Hsu, Sung-Po; Chand, Kuldeep; Yu, Fu-Lun; Tsai, Cheng-Long; Tseng, Yu-Hsuan; Lu, Yuh-Hsiu; Kuo, Jen-Yu; Carey, James R; Chen, Hsuan-Ying; Chen, Hsing-Yin; Chiang, Michael Y; Hsu, Sodio C N

2017-03-06

β-Diketiminato copper(I) complexes play important roles in bioinspired catalytic chemistry and in applications to the materials industry. However, it has been observed that these complexes are very susceptible to disproportionation. Coordinating solvents or Lewis bases are typically used to prevent disproportionation and to block the coordination sites of the copper(I) center from further decomposition. Here, we incorporate this coordination protection directly into the molecule in order to increase the stability and reactivity of these complexes and to discover new copper(I) binding motifs. Here we describe the synthesis, structural characterization, and reactivity of a series of unsymmetrical N-aryl-N'-alkylpyridyl β-diketiminato copper(I) complexes and discuss the structures and reactivity of these complexes with respect to the length of the pyridyl arm. All of the aforementioned unsymmetrical ß-diketiminato copper(I) complexes bind CO reversibly and are stable to disproportionation. The binding ability of CO and the rate of pyridyl ligand decoordination of these copper(I) complexes are directly related to the competition between the degree of puckering of the chelate system and the steric demands of the N-aryl substituent.

Toddlers' Complex Communication: Playfulness from a Secure Base

ERIC Educational Resources Information Center

Alcock, Sophie

2013-01-01

Attachment theory is presented in this article as involving embodied relational processes within complex relational systems. Two narrative-like "events" are represented to illustrate very young children playfully relating -- connecting and communicating inter- and intrasubjectively. The ethnographic-inspired research methods included…

Hydrogeologic processes of large-scale tectonomagmatic complexes in Mongolia-southern Siberia and on Mars

USGS Publications Warehouse

Komatsu, G.; Dohm, J.M.; Hare, T.M.

2004-01-01

Large-scale tectonomagmatic complexes are common on Earth and Mars. Many of these complexes are created or at least influenced by mantle processes, including a wide array of plume types ranging from superplumes to mantle plumes. Among the most prominent complexes, the Mongolian plateau on Earth and the Tharsis bulge on Mars share remarkable similarities in terms of large domal uplifted areas, great rift canyon systems, and widespread volcanism on their surfaces. Water has also played an important role in the development of the two complexes. In general, atmospheric and surface water play a bigger role in the development of the present-day Mongolian plateau than for the Tharsis bulge, as evidenced by highly developed drainages and thick accumulation of sediments in the basins of the Baikal rift system. On the Tharsis bulge, however, water appears to have remained as ground ice except during periods of elevated magmatic activity. Glacial and periglacial processes are well documented for the Mongolian plateau and are also reported for parts of the Tharsis bulge. Ice-magma interactions, which are represented by the formation of subice volcanoes in parts of the Mongolian plateau region, have been reported for the Valles Marineris region of Mars. The complexes are also characterized by cataclysmic floods, but their triggering mechanism may differ: mainly ice-dam failures for the Mongolian plateau and outburst of groundwater for the Tharsis bulge, probably by magma-ice interactions, although ice-dam failures within the Valles Marineris region cannot be ruled out as a possible contributor. Comparative studies of the Mongolian plateau and Tharsis bulge provide excellent opportunities for understanding surface manifestations of plume-driven processes on terrestrial planets and how they interact with hydro-cryospheres. ?? 2004 Geological Society of America.

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.

Symmetry reduction and exact solutions of two higher-dimensional nonlinear evolution equations.

PubMed

Gu, Yongyi; Qi, Jianming

2017-01-01

In this paper, symmetries and symmetry reduction of two higher-dimensional nonlinear evolution equations (NLEEs) are obtained by Lie group method. These NLEEs play an important role in nonlinear sciences. We derive exact solutions to these NLEEs via the [Formula: see text]-expansion method and complex method. Five types of explicit function solutions are constructed, which are rational, exponential, trigonometric, hyperbolic and elliptic function solutions of the variables in the considered equations.

Effects of Pedogenic Fe Oxides on Soil Aggregate-Associated Carbon

NASA Astrophysics Data System (ADS)

Asefaw Berhe, A.; Jin, L.

2017-12-01

Carbon sequestration is intimately related to the soil structure, mainly soil aggregate dynamics. Carbon storage in soil aggregates has been recognized as an important carbon stabilization mechanism in soils. Organic matter and pedogenic Fe oxides are major binding agents that facilitate soil aggregate formation and stability. However, few studies have investigated how different forms of pedogenic Fe oxides can affect soil carbon distribution in different aggregate-size fractions. We investigated sequentially extracted pedogenic Fe oxides (in the order of organically complexed Fe extracted with sodium pyrophosphate, poorly-crystalline Fe oxides extracted with hydroxylamine hydrochloride, and crystalline Fe oxides extracted with dithionite hydrochloride) and determined the amount and nature of C in macroaggregates (2-0.25mm), microaggregates (0.25-0.053mm), and two silt and clay fractions (0.053-0.02mm, and <0.02mm) in Musick soil from Sierra Nevada mountain in California. We also determined how pedogenic Fe oxides affect soil carbon distribution along soil depth gradients. Findings of our study revealed that the proportion of organic matter complexed Fe decreased, but the proportion of crystalline Fe increased with increasing soil depths. Poorly crystalline Fe oxides (e.g. ferrihydrite) was identified as a major Fe oxide in surface soil, whereas crystalline Fe oxides (e.g. goethite) were found in deeper soil layers. These results suggest that high concentration of organic matter in surface soil suppressed Fe crystallization. Calcium cation was closely related to the pyrophosphate extractable Fe and C, which indicates that calcium may be a major cation that contribute to the organic matter complexed Fe and C pool. Increasing concentrations of extractable Fe and C with decreasing aggregate size fractions also suggests that Fe oxides play an important role in formation and stability of silt and clay fractions, and leading to further stabilization of carbon in soil. Our findings provide mechanistic understanding of how pedogenic Fe oxides play important role in carbon stabilization in different aggregate-size fractions in soil.

Integrin-extracellular matrix interactions in connective tissue remodeling and osteoblast differentiation

NASA Technical Reports Server (NTRS)

Globus, R. K.; Moursi, A.; Zimmerman, D.; Lull, J.; Damsky, C.

1995-01-01

The differentiaton of bone cells is a complex multistep process. Bone is somewhat unusual in that it is very actively and continually remodeled in the adult and that maintenance of its mass in the mature organism is exquisitely sensitive to mechanical as well as chemical signals. Bone is also unique because it consists of a very large amount of extracellular matrix (ECM) that is mineralized. The integrin family of ECM receptors has been shown to play an important role in tissue morphogenesis in several systems. Our studies on the regulation of matrix remodeling enzymes by integrins in rabbit synovial fibroblasts show that two b1 integrin fibronectin (FN) receptor complexes (alpha 5 beta 1 and alpha 4 beta 1) cooperate in detecting subtle changes in the composition of the ECM. As a result of signal transduction by these integrins, the levels of mRNA and protein for several members of the metalloproteinase family are regulated in these cells. We have also used antibody and RGD peptide perturbation studies to determine the significance of cell/ECM interactions to normal osteogenesis. We found that interactions between the cell binding domain of FN and integrins are required for both normal morphogenesis and gene expression in cultured osteoblasts that differentiate to form bone-like tissue in culture. These data lead us to propose that beta 1 integrins play an important role in osteoblast differentiation as well as in bone remodeling.

Compatibility art of traditional Chinese medicine: from the perspective of herb pairs.

PubMed

Wang, Shengpeng; Hu, Yangyang; Tan, Wen; Wu, Xu; Chen, Ruie; Cao, Jiliang; Chen, Meiwan; Wang, Yitao

2012-09-28

Over the past decades, research of traditional Chinese medicine (TCM) mainly focused on developing potential candidates from Chinese medicinal herbs, while the wisdom of applying these traditional herbs has not been paid as much attention as it deserves. As is well-known, multi-herb therapy is one of the most important characteristics of TCM, but the modernization drive of this conventional wisdom has faced many obstacles due to its unimaginable complexity. Herb pairs, the most fundamental and the simplest form of multi-herb formulae, are a centralized representative of Chinese herbal compatibility. In light of their simplicity and the basic characteristics of complex formulae, herb pairs are of great importance in the studies of herb compatibility. A systematic search of herb pair related research was carried out using multiple online literature databases, books and monographs published in the past 20 years. A comprehensive introduction to the compatibility of TCM, the position of herb pairs in TCM and the progresses of several famous herb pairs were provided in this review. Furthermore, the clinical study and the future research trends of herb pairs were also discussed. Herb pairs have played, and may continue to play a key role in full investigation of general herb compatibility for their indispensable position in TCM. Much more research is needed for the standardization, safety evaluation, and mechanism exploration of herb pairs. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Dramatic performance of Clostridium thermocellum explained by its wide range of cellulase modalities

DOE PAGES

Xu, Qi; Resch, Michael G.; Podkaminer, Kara; ...

2016-02-05

Clostridium thermocellum is the most efficient microorganism for solubilizing lignocellulosic biomass known to date. Its high cellulose digestion capability is attributed to efficient cellulases consisting of both a free-enzyme system and a tethered cellulosomal system wherein carbohydrate active enzymes (CAZymes) are organized by primary and secondary scaffoldin proteins to generate large protein complexes attached to the bacterial cell wall. This study demonstrates that C. thermocellum also uses a type of cellulosomal system not bound to the bacterial cell wall, called the “cell-free” cellulosomal system. The cell-free cellulosome complex can be seen as a “long range cellulosome” because it can diffusemore » away from the cell and degrade polysaccharide substrates remotely from the bacterial cell. The contribution of these two types of cellulosomal systems in C. thermocellum was elucidated by characterization of mutants with different combinations of scaffoldin gene deletions. The primary scaffoldin, CipA, was found to play the most important role in cellulose degradation by C. thermocellum, whereas the secondary scaffoldins have less important roles. Additionally, the distinct and efficient mode of action of the C. thermocellum exoproteome, wherein the cellulosomes splay or divide biomass particles, changes when either the primary or secondary scaffolds are removed, showing that the intact wild-type cellulosomal system is necessary for this essential mode of action. As a result, this new transcriptional and proteomic evidence shows that a functional primary scaffoldin plays a more important role compared to secondary scaffoldins in the proper regulation of CAZyme genes, cellodextrin transport, and other cellular functions.« less

Heterogeneous nuclear ribonucleoprotein K upregulates the kinetochore complex component NUF2 and promotes the tumorigenicity of colon cancer cells

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

Sugimasa, Hironobu; Taniue, Kenzui; Kurimoto, Akiko

2015-03-27

Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a multi-functional protein involved in transcription, mRNA splicing, mRNA stabilization and translation. Although hnRNP K has been suggested to play a role in the development of many cancers, its molecular function in colorectal cancer has remained elusive. Here we show that hnRNP K plays an important role in the mitotic process in HCT116 colon cancer cells. Furthermore, we demonstrate that hnRNP K directly transactivates the NUF2 gene, the product of which is a component of the NDC80 kinetochore complex and which is known to be critical for a stable spindle microtubule-kinetochore attachment. Inmore » addition, knockdown of both hnRNP K and NUF2 caused failure in metaphase chromosome alignment and drastic decrease in the growth of colon cancer cells. These results suggest that the hnRNP K-NUF2 axis is important for the mitotic process and proliferation of colon cancer cells and that this axis could be a target for the therapy of colon cancer. - Highlights: • hnRNP K is required for the tumorigenicity of colon cancer cells. • hnRNP K binds to the promoter region of NUF2 and activates its transcription. • NUF2 expression is correlated with hnRNP K expression in colorectal cancer tissue. • hnRNP K and NUF2 are required for metaphase chromosome alignment. • The hnRNP K-NUF2 axis is important for the proliferation of colon cancer cells.« less

Dramatic performance of Clostridium thermocellum explained by its wide range of cellulase modalities

PubMed Central

Xu, Qi; Resch, Michael G.; Podkaminer, Kara; Yang, Shihui; Baker, John O.; Donohoe, Bryon S.; Wilson, Charlotte; Klingeman, Dawn M.; Olson, Daniel G.; Decker, Stephen R.; Giannone, Richard J.; Hettich, Robert L.; Brown, Steven D.; Lynd, Lee R.; Bayer, Edward A.; Himmel, Michael E.; Bomble, Yannick J.

2016-01-01

Clostridium thermocellum is the most efficient microorganism for solubilizing lignocellulosic biomass known to date. Its high cellulose digestion capability is attributed to efficient cellulases consisting of both a free-enzyme system and a tethered cellulosomal system wherein carbohydrate active enzymes (CAZymes) are organized by primary and secondary scaffoldin proteins to generate large protein complexes attached to the bacterial cell wall. This study demonstrates that C. thermocellum also uses a type of cellulosomal system not bound to the bacterial cell wall, called the “cell-free” cellulosomal system. The cell-free cellulosome complex can be seen as a “long range cellulosome” because it can diffuse away from the cell and degrade polysaccharide substrates remotely from the bacterial cell. The contribution of these two types of cellulosomal systems in C. thermocellum was elucidated by characterization of mutants with different combinations of scaffoldin gene deletions. The primary scaffoldin, CipA, was found to play the most important role in cellulose degradation by C. thermocellum, whereas the secondary scaffoldins have less important roles. Additionally, the distinct and efficient mode of action of the C. thermocellum exoproteome, wherein the cellulosomes splay or divide biomass particles, changes when either the primary or secondary scaffolds are removed, showing that the intact wild-type cellulosomal system is necessary for this essential mode of action. This new transcriptional and proteomic evidence shows that a functional primary scaffoldin plays a more important role compared to secondary scaffoldins in the proper regulation of CAZyme genes, cellodextrin transport, and other cellular functions. PMID:26989779

Optoelectronic interconnects for 3D wafer stacks

NASA Astrophysics Data System (ADS)

Ludwig, David E.; Carson, John C.; Lome, Louis S.

1996-01-01

Wafer and chip stacking are envisioned as a means of providing increased processing power within the small confines of a three-dimensional structure. Optoelectronic devices can play an important role in these dense 3-D processing electronic packages in two ways. In pure electronic processing, optoelectronics can provide a method for increasing the number of input/output communication channels within the layers of the 3-D chip stack. Non-free space communication links allow the density of highly parallel input/output ports to increase dramatically over typical edge bus connections. In hybrid processors, where electronics and optics play a role in defining the computational algorithm, free space communication links are typically utilized for, among other reasons, the increased network link complexity which can be achieved. Free space optical interconnections provide bandwidths and interconnection complexity unobtainable in pure electrical interconnections. Stacked 3-D architectures can provide the electronics real estate and structure to deal with the increased bandwidth and global information provided by free space optical communications. This paper provides definitions and examples of 3-D stacked architectures in optoelectronics processors. The benefits and issues of these technologies are discussed.

Optoelectronic interconnects for 3D wafer stacks

NASA Astrophysics Data System (ADS)

Ludwig, David; Carson, John C.; Lome, Louis S.

1996-01-01

Wafer and chip stacking are envisioned as means of providing increased processing power within the small confines of a three-dimensional structure. Optoelectronic devices can play an important role in these dense 3-D processing electronic packages in two ways. In pure electronic processing, optoelectronics can provide a method for increasing the number of input/output communication channels within the layers of the 3-D chip stack. Non-free space communication links allow the density of highly parallel input/output ports to increase dramatically over typical edge bus connections. In hybrid processors, where electronics and optics play a role in defining the computational algorithm, free space communication links are typically utilized for, among other reasons, the increased network link complexity which can be achieved. Free space optical interconnections provide bandwidths and interconnection complexity unobtainable in pure electrical interconnections. Stacked 3-D architectures can provide the electronics real estate and structure to deal with the increased bandwidth and global information provided by free space optical communications. This paper will provide definitions and examples of 3-D stacked architectures in optoelectronics processors. The benefits and issues of these technologies will be discussed.

Centromere Protein (CENP)-W Interacts with Heterogeneous Nuclear Ribonucleoprotein (hnRNP) U and May Contribute to Kinetochore-Microtubule Attachment in Mitotic Cells

PubMed Central

Chun, Younghwa; Kim, Raehyung; Lee, Soojin

2016-01-01

Background Recent studies have shown that heterogeneous nuclear ribonucleoprotein U (hnRNP U), a component of the hnRNP complex, contributes to stabilize the kinetochore-microtubule interaction during mitosis. CENP-W was identified as an inner centromere component that plays crucial roles in the formation of a functional kinetochore complex. Results We report that hnRNP U interacts with CENP-W, and the interaction between hnRNP U and CENP-W mutually increased each other’s protein stability by inhibiting the proteasome-mediated degradation. Further, their co-localization was observed chiefly in the nuclear matrix region and at the microtubule-kinetochore interface during interphase and mitosis, respectively. Both microtubule-stabilizing and microtubule-destabilizing agents significantly decreased the protein stability of CENP-W. Furthermore, loss of microtubules and defects in microtubule organization were observed in CENP-W-depleted cells. Conclusion Our data imply that CENP-W plays an important role in the attachment and interaction between microtubules and kinetochore during mitosis. PMID:26881882

Musepick: AN Integrated Technological Framework to Present the Complex of Santissima Annunziata in Ascoli Piceno (italy)

NASA Astrophysics Data System (ADS)

Petrucci, E.; Rossi, D.

2017-05-01

Nowadays, digital media play a central role in a shift towards updated modes of communicating knowledge. In addition to this, the tragic recent events related to the long series of earthquakes that have taken place in central Italy have also, unfortunately, reiterated the need to document and preserve not only the material value of the architectural heritage but also the intangible values related to the events and people that have characterized their history. In this framework, the paper investigates some of the opportunities offered by technological innovations, in particular, by the specific application areas of augmented reality and augmented virtuality. The case study The historical site chosen as case study is the complex of Santissima Annunziata, which has played a very important role in the city of Ascoli Piceno (Italy) for centuries. The objective was to develop a low-cost web-based platform to serve as a place to gather cultural content related to the diffuse cultural heritage, organized in applications regarding graphical and 3D models as well as 360° images and archival documents.

Symbolic play and language development.

PubMed

Orr, Edna; Geva, Ronny

2015-02-01

Symbolic play and language are known to be highly interrelated, but the developmental process involved in this relationship is not clear. Three hypothetical paths were postulated to explore how play and language drive each other: (1) direct paths, whereby initiation of basic forms in symbolic action or babbling, will be directly related to all later emerging language and motor outputs; (2) an indirect interactive path, whereby basic forms in symbolic action will be associated with more complex forms in symbolic play, as well as with babbling, and babbling mediates the relationship between symbolic play and speech; and (3) a dual path, whereby basic forms in symbolic play will be associated with basic forms of language, and complex forms of symbolic play will be associated with complex forms of language. We micro-coded 288 symbolic vignettes gathered during a yearlong prospective bi-weekly examination (N=14; from 6 to 18 months of age). Results showed that the age of initiation of single-object symbolic play correlates strongly with the age of initiation of later-emerging symbolic and vocal outputs; its frequency at initiation is correlated with frequency at initiation of babbling, later-emerging speech, and multi-object play in initiation. Results support the notion that a single-object play relates to the development of other symbolic forms via a direct relationship and an indirect relationship, rather than a dual-path hypothesis. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria.

PubMed

Inaoka, Daniel Ken; Shiba, Tomoo; Sato, Dan; Balogun, Emmanuel Oluwadare; Sasaki, Tsuyoshi; Nagahama, Madoka; Oda, Masatsugu; Matsuoka, Shigeru; Ohmori, Junko; Honma, Teruki; Inoue, Masayuki; Kita, Kiyoshi; Harada, Shigeharu

2015-07-07

Recent studies on the respiratory chain of Ascaris suum showed that the mitochondrial NADH-fumarate reductase system composed of complex I, rhodoquinone and complex II plays an important role in the anaerobic energy metabolism of adult A. suum. The system is the major pathway of energy metabolism for adaptation to a hypoxic environment not only in parasitic organisms, but also in some types of human cancer cells. Thus, enzymes of the pathway are potential targets for chemotherapy. We found that flutolanil is an excellent inhibitor for A. suum complex II (IC50 = 0.058 μM) but less effectively inhibits homologous porcine complex II (IC50 = 45.9 μM). In order to account for the specificity of flutolanil to A. suum complex II from the standpoint of structural biology, we determined the crystal structures of A. suum and porcine complex IIs binding flutolanil and its derivative compounds. The structures clearly demonstrated key interactions responsible for its high specificity to A. suum complex II and enabled us to find analogue compounds, which surpass flutolanil in both potency and specificity to A. suum complex II. Structures of complex IIs binding these compounds will be helpful to accelerate structure-based drug design targeted for complex IIs.

Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria

PubMed Central

Inaoka, Daniel Ken; Shiba, Tomoo; Sato, Dan; Balogun, Emmanuel Oluwadare; Sasaki, Tsuyoshi; Nagahama, Madoka; Oda, Masatsugu; Matsuoka, Shigeru; Ohmori, Junko; Honma, Teruki; Inoue, Masayuki; Kita, Kiyoshi; Harada, Shigeharu

2015-01-01

Recent studies on the respiratory chain of Ascaris suum showed that the mitochondrial NADH-fumarate reductase system composed of complex I, rhodoquinone and complex II plays an important role in the anaerobic energy metabolism of adult A. suum. The system is the major pathway of energy metabolism for adaptation to a hypoxic environment not only in parasitic organisms, but also in some types of human cancer cells. Thus, enzymes of the pathway are potential targets for chemotherapy. We found that flutolanil is an excellent inhibitor for A. suum complex II (IC50 = 0.058 μM) but less effectively inhibits homologous porcine complex II (IC50 = 45.9 μM). In order to account for the specificity of flutolanil to A. suum complex II from the standpoint of structural biology, we determined the crystal structures of A. suum and porcine complex IIs binding flutolanil and its derivative compounds. The structures clearly demonstrated key interactions responsible for its high specificity to A. suum complex II and enabled us to find analogue compounds, which surpass flutolanil in both potency and specificity to A. suum complex II. Structures of complex IIs binding these compounds will be helpful to accelerate structure-based drug design targeted for complex IIs. PMID:26198225

Soot and Spectral Radiation Modeling in ECN Spray A and in Engines

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

Haworth, Daniel C; Ferreyro-Fernandez, Sebastian; Paul, Chandan

The amount of soot formed in a turbulent combustion system is determined by a complex system of coupled nonlinear chemical and physical processes. Different physical subprocesses can dominate, depending on the hydrodynamic and thermochemical environments. Similarly, the relative importance of reabsorption, spectral radiation properties, and molecular gas radiation versus soot radiation varies with thermochemical conditions, and in ways that are difficult to predict for the highly nonhomogeneous in-cylinder mixtures in engines. Here it is shown that transport and mixing play relatively more important roles as rate-determining processes in soot formation at engine-relevant conditions. It is also shown that molecular gasmore » radiation and spectral radiation properties are important for engine-relevant conditions.« less

The role of positively charged amino acids and electrostatic interactions in the complex of U1A protein and U1 hairpin II RNA

PubMed Central

Law, Michael J.; Linde, Michael E.; Chambers, Eric J.; Oubridge, Chris; Katsamba, Phinikoula S.; Nilsson, Lennart; Haworth, Ian S.; Laird-Offringa, Ite A.

2006-01-01

Previous kinetic investigations of the N-terminal RNA recognition motif (RRM) domain of spliceosomal protein U1A, interacting with its RNA target U1 hairpin II, provided experimental evidence for a ‘lure and lock’ model of binding in which electrostatic interactions first guide the RNA to the protein, and close range interactions then lock the two molecules together. To further investigate the ‘lure’ step, here we examined the electrostatic roles of two sets of positively charged amino acids in U1A that do not make hydrogen bonds to the RNA: Lys20, Lys22 and Lys23 close to the RNA-binding site, and Arg7, Lys60 and Arg70, located on ‘top’ of the RRM domain, away from the RNA. Surface plasmon resonance-based kinetic studies, supplemented with salt dependence experiments and molecular dynamics simulation, indicate that Lys20 predominantly plays a role in association, while nearby residues Lys22 and Lys23 appear to be at least as important for complex stability. In contrast, kinetic analyses of residues away from the RNA indicate that they have a minimal effect on association and stability. Thus, well-positioned positively charged residues can be important for both initial complex formation and complex maintenance, illustrating the multiple roles of electrostatic interactions in protein–RNA complexes. PMID:16407334

Activation of Dioxygen by Iron and Manganese Complexes: A Heme and Nonheme Perspective

PubMed Central

Sahu, Sumit; Goldberg, David P.

2016-01-01

The rational design of well-defined, first-row transition metal complexes that can activate dioxygen has been a challenging goal for the synthetic inorganic chemist. The activation of O2 is important in part because of its central role in the functioning of metalloenzymes, which utilize O2 to perform a number of challenging reactions including the highly selective oxidation of various substrates. There is also great interest in utilizing O2, an abundant and environmentally benign oxidant, in synthetic catalytic oxidation systems. This Perspective brings together recent examples of biomimetic Fe and Mn complexes that can activate O2 in heme or nonheme-type ligand environments. The use of oxidants such as hypervalent iodine (e.g., ArIO), peracids (e.g., m-CPBA), peroxides (e.g., H2O2) or even superoxide is a popular choice for accessing well-characterized metal–superoxo, metal–peroxo, or metal–oxo species, but the instances of biomimetic Fe/Mn complexes that react with dioxygen to yield such observable metal–oxygen species are surprisingly few. This Perspective focuses on mononuclear Fe and Mn complexes that exhibit reactivity with O2 and lead to spectroscopically observable metal–oxygen species, and/or oxidize biologically relevant substrates. Analysis of these examples reveals that solvent, spin state, redox potential, external co-reductants, and ligand architecture can all play important roles in the O2 activation process. PMID:27576170

Structure-activity relationships of mononuclear metal-thiosemicarbazone complexes endowed with potent antiplasmodial and antiamoebic activities.

PubMed

Bahl, Deepa; Athar, Fareeda; Soares, Milena Botelho Pereira; de Sá, Matheus Santos; Moreira, Diogo Rodrigo Magalhães; Srivastava, Rajendra Mohan; Leite, Ana Cristina Lima; Azam, Amir

2010-09-15

A useful concept for the rational design of antiparasitic drug candidates is the complexation of bioactive ligands with transition metals. In view of this, an investigation was conducted into a new set of metal complexes as potential antiplasmodium and antiamoebic agents, in order to examine the importance of metallic atoms, as well as the kind of sphere of co-ordination, in these biological properties. Four functionalized furyl-thiosemicarbazones (NT1-4) treated with divalent metals (Cu, Co, Pt, and Pd) to form the mononuclear metallic complexes of formula [M(L)2Cl2] or [M(L)Cl2] were examined. The pharmacological characterization, including assays against Plasmodium falciparum and Entamoeba histolytica, cytotoxicity to mammalian cells, and interaction with pBR 322 plasmid DNA was performed. Structure-activity relationship data revealed that the metallic complexation plays an essential role in antiprotozoal activity, rather than the simple presence of the ligand or metal alone. Important steps towards identification of novel antiplasmodium (NT1Cu, IC50 of 4.6 microM) and antiamoebic (NT2Pd, IC50 of 0.6 microM) drug prototypes were achieved. Of particular relevance to this work, these prototypes were able to reduce the proliferation of these parasites at concentrations that are not cytotoxic to mammalian cells. Copyright (c) 2010. Published by Elsevier Ltd.

Cardiolipin synthesizing enzymes form a complex that interacts with cardiolipin-dependent membrane organizing proteins.

PubMed

Serricchio, Mauro; Vissa, Adriano; Kim, Peter K; Yip, Christopher M; McQuibban, G Angus

2018-04-01

The mitochondrial glycerophospholipid cardiolipin plays important roles in mitochondrial biology. Most notably, cardiolipin directly binds to mitochondrial proteins and helps assemble and stabilize mitochondrial multi-protein complexes. Despite their importance for mitochondrial health, how the proteins involved in cardiolipin biosynthesis are organized and embedded in mitochondrial membranes has not been investigated in detail. Here we show that human PGS1 and CLS1 are constituents of large protein complexes. We show that PGS1 forms oligomers and associates with CLS1 and PTPMT1. Using super-resolution microscopy, we observed well-organized nanoscale structures formed by PGS1. Together with the observation that cardiolipin and CLS1 are not required for PGS1 to assemble in the complex we predict the presence of a PGS1-centered cardiolipin-synthesizing scaffold within the mitochondrial inner membrane. Using an unbiased proteomic approach we found that PGS1 and CLS1 interact with multiple cardiolipin-binding mitochondrial membrane proteins, including prohibitins, stomatin-like protein 2 and the MICOS components MIC60 and MIC19. We further mapped the protein-protein interaction sites between PGS1 and itself, CLS1, MIC60 and PHB. Overall, this study provides evidence for the presence of a cardiolipin synthesis structure that transiently interacts with cardiolipin-dependent protein complexes. Copyright © 2018 Elsevier B.V. All rights reserved.

The temporo-parietal junction contributes to global gestalt perception-evidence from studies in chess experts.

PubMed

Rennig, Johannes; Bilalić, Merim; Huberle, Elisabeth; Karnath, Hans-Otto; Himmelbach, Marc

2013-01-01

In a recent neuroimaging study the comparison of intact vs. disturbed perception of global gestalt indicated a significant role of the temporo-parietal junction (TPJ) in the intact perception of global gestalt (Huberle and Karnath, 2012). This location corresponded well with the areas known to be damaged or impaired in patients with simultanagnosia after stroke or due to neurodegenerative diseases. It was concluded that the TPJ plays an important role in the integration of individual items to a holistic percept. Thus, increased BOLD signals should be found in this region whenever a task calls for the integration of multiple visual items. Behavioral experiments in chess experts suggested that their superior skills in comparison to chess novices are partly based on fast holistic processing of chess positions with multiple pieces. We thus analyzed BOLD data from four fMRI studies that compared chess experts with chess novices during the presentation of complex chess-related visual stimuli (Bilalić et al., 2010, 2011a,b, 2012). Three regions of interests were defined by significant TPJ clusters in the abovementioned study of global gestalt perception (Huberle and Karnath, 2012) and BOLD signal amplitudes in these regions were compared between chess experts and novices. These cross-paradigm ROI analyses revealed higher signals at the TPJ in chess experts in comparison to novices during presentations of complex chess positions. This difference was consistent across the different tasks in five independent experiments. Our results confirm the assumption that the TPJ region identified in previous work on global gestalt perception plays an important role in the processing of complex visual stimulus configurations.

The temporo-parietal junction contributes to global gestalt perception—evidence from studies in chess experts

PubMed Central

Rennig, Johannes; Bilalić, Merim; Huberle, Elisabeth; Karnath, Hans-Otto; Himmelbach, Marc

2013-01-01

In a recent neuroimaging study the comparison of intact vs. disturbed perception of global gestalt indicated a significant role of the temporo-parietal junction (TPJ) in the intact perception of global gestalt (Huberle and Karnath, 2012). This location corresponded well with the areas known to be damaged or impaired in patients with simultanagnosia after stroke or due to neurodegenerative diseases. It was concluded that the TPJ plays an important role in the integration of individual items to a holistic percept. Thus, increased BOLD signals should be found in this region whenever a task calls for the integration of multiple visual items. Behavioral experiments in chess experts suggested that their superior skills in comparison to chess novices are partly based on fast holistic processing of chess positions with multiple pieces. We thus analyzed BOLD data from four fMRI studies that compared chess experts with chess novices during the presentation of complex chess-related visual stimuli (Bilalić et al., 2010, 2011a,b, 2012). Three regions of interests were defined by significant TPJ clusters in the abovementioned study of global gestalt perception (Huberle and Karnath, 2012) and BOLD signal amplitudes in these regions were compared between chess experts and novices. These cross-paradigm ROI analyses revealed higher signals at the TPJ in chess experts in comparison to novices during presentations of complex chess positions. This difference was consistent across the different tasks in five independent experiments. Our results confirm the assumption that the TPJ region identified in previous work on global gestalt perception plays an important role in the processing of complex visual stimulus configurations. PMID:24009574

Computational Study of the Binding Mechanism of Actin-Depolymerizing Factor 1 with Actin in Arabidopsis thaliana.

PubMed

Du, Juan; Wang, Xue; Dong, Chun-Hai; Yang, Jian Ming; Yao, Xiao Jun

2016-01-01

Actin is a highly conserved protein. It plays important roles in cellular function and exists either in the monomeric (G-actin) or polymeric form (F-actin). Members of the actin-depolymerizing factor (ADF)/cofilin protein family bind to both G-actin and F-actin and play vital roles in actin dynamics by manipulating the rates of filament polymerization and depolymerization. It has been reported that the S6D and R98A/K100A mutants of actin-depolymerizing factor 1 (ADF1) in Arabidopsis thaliana decreased the binding affinity of ADF for the actin monomer. To investigate the binding mechanism and dynamic behavior of the ADF1-actin complex, we constructed a homology model of the AtADF1-actin complex based on the crystal structure of AtADF1 and the twinfilin C-terminal ADF-H domain in a complex with a mouse actin monomer. The model was then refined for subsequent molecular dynamics simulations. Increased binding energy of the mutated system was observed using the Molecular Mechanics Generalized Born Surface Area and Poisson-Boltzmann Surface Area (MM-GB/PBSA) methods. To determine the residues that make decisive contributions to the ADF1 actin-binding affinity, per-residue decomposition and computational alanine scanning analyses were performed, which provided more detailed information on the binding mechanism. Root-mean-square fluctuation and principal component analyses confirmed that the S6D and R98A/K100A mutants induced an increased conformational flexibility. The comprehensive molecular insight gained from this study is of great importance for understanding the binding mechanism of ADF1 and G-actin.

Computational Study of the Binding Mechanism of Actin-Depolymerizing Factor 1 with Actin in Arabidopsis thaliana

PubMed Central

Wang, Xue; Dong, Chun-Hai; Yang, Jian Ming; Yao, Xiao Jun

2016-01-01

Actin is a highly conserved protein. It plays important roles in cellular function and exists either in the monomeric (G-actin) or polymeric form (F-actin). Members of the actin-depolymerizing factor (ADF)/cofilin protein family bind to both G-actin and F-actin and play vital roles in actin dynamics by manipulating the rates of filament polymerization and depolymerization. It has been reported that the S6D and R98A/K100A mutants of actin-depolymerizing factor 1 (ADF1) in Arabidopsis thaliana decreased the binding affinity of ADF for the actin monomer. To investigate the binding mechanism and dynamic behavior of the ADF1–actin complex, we constructed a homology model of the AtADF1–actin complex based on the crystal structure of AtADF1 and the twinfilin C-terminal ADF-H domain in a complex with a mouse actin monomer. The model was then refined for subsequent molecular dynamics simulations. Increased binding energy of the mutated system was observed using the Molecular Mechanics Generalized Born Surface Area and Poisson–Boltzmann Surface Area (MM-GB/PBSA) methods. To determine the residues that make decisive contributions to the ADF1 actin-binding affinity, per-residue decomposition and computational alanine scanning analyses were performed, which provided more detailed information on the binding mechanism. Root-mean-square fluctuation and principal component analyses confirmed that the S6D and R98A/K100A mutants induced an increased conformational flexibility. The comprehensive molecular insight gained from this study is of great importance for understanding the binding mechanism of ADF1 and G-actin. PMID:27414648

The Multivariate Temporal Response Function (mTRF) Toolbox: A MATLAB Toolbox for Relating Neural Signals to Continuous Stimuli.

PubMed

Crosse, Michael J; Di Liberto, Giovanni M; Bednar, Adam; Lalor, Edmund C

2016-01-01

Understanding how brains process sensory signals in natural environments is one of the key goals of twenty-first century neuroscience. While brain imaging and invasive electrophysiology will play key roles in this endeavor, there is also an important role to be played by noninvasive, macroscopic techniques with high temporal resolution such as electro- and magnetoencephalography. But challenges exist in determining how best to analyze such complex, time-varying neural responses to complex, time-varying and multivariate natural sensory stimuli. There has been a long history of applying system identification techniques to relate the firing activity of neurons to complex sensory stimuli and such techniques are now seeing increased application to EEG and MEG data. One particular example involves fitting a filter-often referred to as a temporal response function-that describes a mapping between some feature(s) of a sensory stimulus and the neural response. Here, we first briefly review the history of these system identification approaches and describe a specific technique for deriving temporal response functions known as regularized linear regression. We then introduce a new open-source toolbox for performing this analysis. We describe how it can be used to derive (multivariate) temporal response functions describing a mapping between stimulus and response in both directions. We also explain the importance of regularizing the analysis and how this regularization can be optimized for a particular dataset. We then outline specifically how the toolbox implements these analyses and provide several examples of the types of results that the toolbox can produce. Finally, we consider some of the limitations of the toolbox and opportunities for future development and application.

The Multivariate Temporal Response Function (mTRF) Toolbox: A MATLAB Toolbox for Relating Neural Signals to Continuous Stimuli

PubMed Central

Crosse, Michael J.; Di Liberto, Giovanni M.; Bednar, Adam; Lalor, Edmund C.

2016-01-01

Understanding how brains process sensory signals in natural environments is one of the key goals of twenty-first century neuroscience. While brain imaging and invasive electrophysiology will play key roles in this endeavor, there is also an important role to be played by noninvasive, macroscopic techniques with high temporal resolution such as electro- and magnetoencephalography. But challenges exist in determining how best to analyze such complex, time-varying neural responses to complex, time-varying and multivariate natural sensory stimuli. There has been a long history of applying system identification techniques to relate the firing activity of neurons to complex sensory stimuli and such techniques are now seeing increased application to EEG and MEG data. One particular example involves fitting a filter—often referred to as a temporal response function—that describes a mapping between some feature(s) of a sensory stimulus and the neural response. Here, we first briefly review the history of these system identification approaches and describe a specific technique for deriving temporal response functions known as regularized linear regression. We then introduce a new open-source toolbox for performing this analysis. We describe how it can be used to derive (multivariate) temporal response functions describing a mapping between stimulus and response in both directions. We also explain the importance of regularizing the analysis and how this regularization can be optimized for a particular dataset. We then outline specifically how the toolbox implements these analyses and provide several examples of the types of results that the toolbox can produce. Finally, we consider some of the limitations of the toolbox and opportunities for future development and application. PMID:27965557

Stepping into the omics era: Opportunities and challenges for biomaterials science and engineering☆

PubMed Central

Rabitz, Herschel; Welsh, William J.; Kohn, Joachim; de Boer, Jan

2016-01-01

The research paradigm in biomaterials science and engineering is evolving from using low-throughput and iterative experimental designs towards high-throughput experimental designs for materials optimization and the evaluation of materials properties. Computational science plays an important role in this transition. With the emergence of the omics approach in the biomaterials field, referred to as materiomics, high-throughput approaches hold the promise of tackling the complexity of materials and understanding correlations between material properties and their effects on complex biological systems. The intrinsic complexity of biological systems is an important factor that is often oversimplified when characterizing biological responses to materials and establishing property-activity relationships. Indeed, in vitro tests designed to predict in vivo performance of a given biomaterial are largely lacking as we are not able to capture the biological complexity of whole tissues in an in vitro model. In this opinion paper, we explain how we reached our opinion that converging genomics and materiomics into a new field would enable a significant acceleration of the development of new and improved medical devices. The use of computational modeling to correlate high-throughput gene expression profiling with high throughput combinatorial material design strategies would add power to the analysis of biological effects induced by material properties. We believe that this extra layer of complexity on top of high-throughput material experimentation is necessary to tackle the biological complexity and further advance the biomaterials field. PMID:26876875

On the Importance of Polar Interactions for Complexes Containing Intrinsically Disordered Proteins

PubMed Central

Wong, Eric T. C.; Na, Dokyun; Gsponer, Jörg

2013-01-01

There is a growing recognition for the importance of proteins with large intrinsically disordered (ID) segments in cell signaling and regulation. ID segments in these proteins often harbor regions that mediate molecular recognition. Coupled folding and binding of the recognition regions has been proposed to confer high specificity to interactions involving ID segments. However, researchers recently questioned the origin of the interaction specificity of ID proteins because of the overrepresentation of hydrophobic residues in their interaction interfaces. Here, we focused on the role of polar and charged residues in interactions mediated by ID segments. Making use of the extended nature of most ID segments when in complex with globular proteins, we first identified large numbers of complexes between globular proteins and ID segments by using radius-of-gyration-based selection criteria. Consistent with previous studies, we found the interfaces of these complexes to be enriched in hydrophobic residues, and that these residues contribute significantly to the stability of the interaction interface. However, our analyses also show that polar interactions play a larger role in these complexes than in structured protein complexes. Computational alanine scanning and salt-bridge analysis indicate that interfaces in ID complexes are highly complementary with respect to electrostatics, more so than interfaces of globular proteins. Follow-up calculations of the electrostatic contributions to the free energy of binding uncovered significantly stronger Coulombic interactions in complexes harbouring ID segments than in structured protein complexes. However, they are counter-balanced by even higher polar-desolvation penalties. We propose that polar interactions are a key contributing factor to the observed high specificity of ID segment-mediated interactions. PMID:23990768

Community Detection in Complex Networks via Clique Conductance.

PubMed

Lu, Zhenqi; Wahlström, Johan; Nehorai, Arye

2018-04-13

Network science plays a central role in understanding and modeling complex systems in many areas including physics, sociology, biology, computer science, economics, politics, and neuroscience. One of the most important features of networks is community structure, i.e., clustering of nodes that are locally densely interconnected. Communities reveal the hierarchical organization of nodes, and detecting communities is of great importance in the study of complex systems. Most existing community-detection methods consider low-order connection patterns at the level of individual links. But high-order connection patterns, at the level of small subnetworks, are generally not considered. In this paper, we develop a novel community-detection method based on cliques, i.e., local complete subnetworks. The proposed method overcomes the deficiencies of previous similar community-detection methods by considering the mathematical properties of cliques. We apply the proposed method to computer-generated graphs and real-world network datasets. When applied to networks with known community structure, the proposed method detects the structure with high fidelity and sensitivity. When applied to networks with no a priori information regarding community structure, the proposed method yields insightful results revealing the organization of these complex networks. We also show that the proposed method is guaranteed to detect near-optimal clusters in the bipartition case.

Current Soviet exploration plays: Success and potential

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

Grace, J.D.

1991-03-01

Soviet hydrocarbon exploration in the 1980s took four distinct directions. First was extension exploration and the search for smaller new fields in discrete traps in traditional producing regions, such as the Apsheron Peninsula, North Caucasus, and Volga-Urals. This strategy produced a large number of small discoveries close to established infrastructure. Second was new field exploration in West Siberia in the stratigraphically complex Jurassic and the lower Neocomian sections. Third was expansion of the prolific gas plays in northern West Siberia. Exploratory success in West Siberia has created a backlog of several hundred discoveries awaiting full delineation and development. Most ofmore » these fields are distant from the established oil production center in the Middle Ob region and, therefore, may remain in inventory. Fourth was initial tests of new exploration frontiers, most important, the Paleozoic and Mesozoic plays of the Barents and Kara seas and the subsalt plays of the North Caspian basin. While these plays have yielded very important discoveries, significant technological barriers impede their development. The outlook for Soviet oil exploration in the 1990s is for significant opportunities for discovery of large volumes of oil, but at radically increasing exploration and production costs. In established regions, these costs arise from small field sizes and low well productivities. In frontier regions, exploitation of new fields will require technology not currently available in the USSR. The outlook for gas exploration continues to be very bright, as the onshore northern West Siberia is not fully explored and initial results from the Barents and Kara seas promise more very large gas discoveries.« less

Protein intrinsic disorder in plants.

PubMed

Pazos, Florencio; Pietrosemoli, Natalia; García-Martín, Juan A; Solano, Roberto

2013-09-12

To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional) form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disordered proteins allows them to bind multiple partners in transient interactions of high specificity and low affinity. In concordance, in plants this type of proteins has been found in processes requiring these complex and versatile interaction networks. These include transcription factor networks, where disordered proteins act as integrators of different signals or link different transcription factor subnetworks due to their ability to interact (in many cases simultaneously) with different partners. Similarly, they also serve as signal integrators in signaling cascades, such as those related to response to external stimuli. Disordered proteins have also been found in plants in many stress-response processes, acting as protein chaperones or protecting other cellular components and structures. In plants, it is especially important to have complex and versatile networks able to quickly and efficiently respond to changing environmental conditions since these organisms cannot escape and have no other choice than adapting to them. Consequently, protein disorder can play an especially important role in plants, providing them with a fast mechanism to obtain complex, interconnected and versatile molecular networks.

Protein intrinsic disorder in plants

PubMed Central

Pazos, Florencio; Pietrosemoli, Natalia; García-Martín, Juan A.; Solano, Roberto

2013-01-01

To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional) form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disordered proteins allows them to bind multiple partners in transient interactions of high specificity and low affinity. In concordance, in plants this type of proteins has been found in processes requiring these complex and versatile interaction networks. These include transcription factor networks, where disordered proteins act as integrators of different signals or link different transcription factor subnetworks due to their ability to interact (in many cases simultaneously) with different partners. Similarly, they also serve as signal integrators in signaling cascades, such as those related to response to external stimuli. Disordered proteins have also been found in plants in many stress-response processes, acting as protein chaperones or protecting other cellular components and structures. In plants, it is especially important to have complex and versatile networks able to quickly and efficiently respond to changing environmental conditions since these organisms cannot escape and have no other choice than adapting to them. Consequently, protein disorder can play an especially important role in plants, providing them with a fast mechanism to obtain complex, interconnected and versatile molecular networks. PMID:24062761

Nucleocytoplasmic Transport of RNAs and RNA-Protein Complexes.

PubMed

Sloan, Katherine E; Gleizes, Pierre-Emmanuel; Bohnsack, Markus T

2016-05-22

RNAs and ribonucleoprotein complexes (RNPs) play key roles in mediating and regulating gene expression. In eukaryotes, most RNAs are transcribed, processed and assembled with proteins in the nucleus and then either function in the cytoplasm or also undergo a cytoplasmic phase in their biogenesis. This compartmentalization ensures that sequential steps in gene expression and RNP production are performed in the correct order and it allows important quality control mechanisms that prevent the involvement of aberrant RNAs/RNPs in these cellular pathways. The selective exchange of RNAs/RNPs between the nucleus and cytoplasm is enabled by nuclear pore complexes, which function as gateways between these compartments. RNA/RNP transport is facilitated by a range of nuclear transport receptors and adaptors, which are specifically recruited to their cargos and mediate interactions with nucleoporins to allow directional translocation through nuclear pore complexes. While some transport factors are only responsible for the export/import of a certain class of RNA/RNP, others are multifunctional and, in the case of large RNPs, several export factors appear to work together to bring about export. Recent structural studies have revealed aspects of the mechanisms employed by transport receptors to enable specific cargo recognition, and genome-wide approaches have provided the first insights into the diverse composition of pre-mRNPs during export. Furthermore, the regulation of RNA/RNP export is emerging as an important means to modulate gene expression under stress conditions and in disease. Copyright © 2015. Published by Elsevier Ltd.

Optimal dimensionality reduction of complex dynamics: the chess game as diffusion on a free-energy landscape.

PubMed

Krivov, Sergei V

2011-07-01

Dimensionality reduction is ubiquitous in the analysis of complex dynamics. The conventional dimensionality reduction techniques, however, focus on reproducing the underlying configuration space, rather than the dynamics itself. The constructed low-dimensional space does not provide a complete and accurate description of the dynamics. Here I describe how to perform dimensionality reduction while preserving the essential properties of the dynamics. The approach is illustrated by analyzing the chess game--the archetype of complex dynamics. A variable that provides complete and accurate description of chess dynamics is constructed. The winning probability is predicted by describing the game as a random walk on the free-energy landscape associated with the variable. The approach suggests a possible way of obtaining a simple yet accurate description of many important complex phenomena. The analysis of the chess game shows that the approach can quantitatively describe the dynamics of processes where human decision-making plays a central role, e.g., financial and social dynamics.

Phosphorus dendrimers and photodynamic therapy. Spectroscopic studies on two dendrimer-photosensitizer complexes: Cationic phosphorus dendrimer with rose bengal and anionic phosphorus dendrimer with methylene blue.

PubMed

Dabrzalska, Monika; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

2015-08-15

Dendrimers due to their unique architecture may play an important role in drug delivery systems including chemotherapy, gene therapy and recently, photodynamic therapy as well. We investigated two dendrimer-photosensitizer systems in context of potential use of these systems in photodynamic therapy. The mixtures of an anionic phosphorus dendrimer of the second generation and methylene blue were studied by UV-vis spectroscopy while that of a cationic phosphorus dendrimer (third generation) and rose bengal were investigated by spectrofluorimetric methods. Spectroscopic analysis of these two systems revealed the formation of dendrimer-photosensitizer complexes via electrostatic interactions as well as π stacking. The stoichiometry of the rose bengal-cationic dendrimer complex was estimated to be 7:1 and 9:1 for the methylene blue-anionic dendrimer complex. The results suggest that these polyanionic or polycationic phosphorus dendrimers can be promising candidates as carriers in photodynamic therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

Complex formation of blueberry (Vaccinium angustifolium) anthocyanins during freeze-drying and its influence on their biological activity.

PubMed

Correa-Betanzo, Julieta; Padmanabhan, Priya; Corredig, Milena; Subramanian, Jayasankar; Paliyath, Gopinadhan

2015-03-25

Biological activity of polyphenols is influenced by their uptake and is highly influenced by their interactions with the food matrix. This study evaluated the complex formation of blueberry polyphenols with fruit matrixes such as pectin and cellulose and their effect on the biological and antiproliferative properties of human colon cell lines HT-29 and CRL 1790. Free or complexed polyphenols were isolated by dialyzing aqueous or methanolic blueberry homogenates. Seven phenolic compounds and thirteen anthocyanins were identified in blueberry extracts. Blueberry extracts showed varying degrees of antioxidant and antiproliferative activities, as well as α-glucosidase activity. Fruit matrix containing cellulose and pectin, or purified polygalacturonic acid and cellulose, did not retain polyphenols and showed very low antioxidant or antiproliferative activities. These findings suggest that interactions between polyphenols and the food matrix may be more complex than a simple association and may play an important role in the bioefficacy of blueberry polyphenols.

Charge Inversion by Electrostatic Complexation: Molecular Dynamics Simulations

NASA Astrophysics Data System (ADS)

Faraudo, Jordi; Travesset, Alex

2007-03-01

Ions near interfaces play an important role in many biological and physico-chemical processes and exhibit a fascinating diverse range of phenomena. A relevant example is charge inversion, where interfacial charges attract counterions in excess of their own nominal charge, thus leading to an inversion of the sign of the interfacial charge. In this work, we argue that in the case of amphiphilic interfaces, charge inversion can be generated by complexation, that is, electrostatic complexes containing several counterions bound to amphiphilic molecules. The formation of these complexes require the presence at the interface of groups with conformational degrees of freedom with many electronegative atoms. We illustrate this mechanism by analyzing all atomic molecular dynamics simulations of a DMPA (Dimirystoil-Phosphatidic acid) phospholipid monolayer in contact with divalent counterions. The results are found to be in agreement with recent experimental results on Langmuir monolayers. We also discuss the implications for biological systems, as Phosphatidic acid is emerging as a key signaling phospholipid.

Three-Dimensional Mapping of Air Flow at an Urban Canyon Intersection

NASA Astrophysics Data System (ADS)

Carpentieri, Matteo; Robins, Alan G.; Baldi, Sandro

2009-11-01

In this experimental work both qualitative (flow visualisation) and quantitative (laser Doppler anemometry) methods were applied in a wind tunnel in order to describe the complex three-dimensional flow field in a real environment (a street canyon intersection). The main aim was an examination of the mean flow, turbulence and flow pathlines characterising a complex three-dimensional urban location. The experiments highlighted the complexity of the observed flows, particularly in the upwind region of the intersection. In this complex and realistic situation some details of the upwind flow, such as the presence of two tall towers, play an important role in defining the flow field within the intersection, particularly at roof level. This effect is likely to have a strong influence on the mass exchange mechanism between the canopy flow and the air aloft, and therefore the distribution of pollutants. This strong interaction between the flows inside and outside the urban canopy is currently neglected in most state-of-the-art local scale dispersion models.

Predictive Surface Complexation Modeling

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

Sverjensky, Dimitri A.

Surface complexation plays an important role in the equilibria and kinetics of processes controlling the compositions of soilwaters and groundwaters, the fate of contaminants in groundwaters, and the subsurface storage of CO 2 and nuclear waste. Over the last several decades, many dozens of individual experimental studies have addressed aspects of surface complexation that have contributed to an increased understanding of its role in natural systems. However, there has been no previous attempt to develop a model of surface complexation that can be used to link all the experimental studies in order to place them on a predictive basis. Overall,more » my research has successfully integrated the results of the work of many experimentalists published over several decades. For the first time in studies of the geochemistry of the mineral-water interface, a practical predictive capability for modeling has become available. The predictive correlations developed in my research now enable extrapolations of experimental studies to provide estimates of surface chemistry for systems not yet studied experimentally and for natural and anthropogenically perturbed systems.« less

DNA Origami Scaffolds as Templates for Functional Tetrameric Kir3 K+ Channels.

PubMed

Kurokawa, Tatsuki; Kiyonaka, Shigeki; Nakata, Eiji; Endo, Masayuki; Koyama, Shohei; Mori, Emiko; Tran, Nam Ha; Dinh, Huyen; Suzuki, Yuki; Hidaka, Kumi; Kawata, Masaaki; Sato, Chikara; Sugiyama, Hiroshi; Morii, Takashi; Mori, Yasuo

2018-03-01

In native systems, scaffolding proteins play important roles in assembling proteins into complexes to transduce signals. This concept is yet to be applied to the assembly of functional transmembrane protein complexes in artificial systems. To address this issue, DNA origami has the potential to serve as scaffolds that arrange proteins at specific positions in complexes. Herein, we report that Kir3 K + channel proteins are assembled through zinc-finger protein (ZFP)-adaptors at specific locations on DNA origami scaffolds. Specific binding of the ZFP-fused Kir3 channels and ZFP-based adaptors on DNA origami were confirmed by atomic force microscopy and gel electrophoresis. Furthermore, the DNA origami with ZFP binding sites nearly tripled the K + channel current activity elicited by heterotetrameric Kir3 channels in HEK293T cells. Thus, our method provides a useful template to control the oligomerization states of membrane protein complexes in vitro and in living cells. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural insights into the histone H1-nucleosome complex

PubMed Central

Zhou, Bing-Rui; Feng, Hanqiao; Kato, Hidenori; Dai, Liang; Yang, Yuedong; Zhou, Yaoqi; Bai, Yawen

2013-01-01

Linker H1 histones facilitate formation of higher-order chromatin structures and play important roles in various cell functions. Despite several decades of effort, the structural basis of how H1 interacts with the nucleosome remains elusive. Here, we investigated Drosophila H1 in complex with the nucleosome, using solution nuclear magnetic resonance spectroscopy and other biophysical methods. We found that the globular domain of H1 bridges the nucleosome core and one 10-base pair linker DNA asymmetrically, with its α3 helix facing the nucleosomal DNA near the dyad axis. Two short regions in the C-terminal tail of H1 and the C-terminal tail of one of the two H2A histones are also involved in the formation of the H1–nucleosome complex. Our results lead to a residue-specific structural model for the globular domain of the Drosophila H1 in complex with the nucleosome, which is different from all previous experiment-based models and has implications for chromatin dynamics in vivo. PMID:24218562

Anion-π interaction in metal-organic networks formed by metal halides and tetracyanopyrazine

NASA Astrophysics Data System (ADS)

Rosokha, Sergiy V.; Kumar, Amar

2017-06-01

Co-crystallization of tetracyanopyrazine, TCP, with the tetraalkylammonium salts of linear [CuBr2]-, planar [PtCl4]2- or [Pt2Br6]2-, or octahedral [PtBr6]2- complexes resulted in formation of the alternating [MlXn]m-/TCP stacks separated by the Alk4N+ cations. These hybrid stacks showed multiple short contacts between halide ligands of the [MlXn]m- complexes and carbon atoms of the TCP acceptor indicating strong anion-π bonding between these species. It confirmed that the anion-π interaction is sufficiently strong to bring together such disparate components as ionic metal complexes and neutral aromatic molecules regardless of the geometry of the coordination compound. Structural features of the solid-state stacks and [MlXn]m-·TCP dyads resulted from the quantum-mechanical computations suggests that the molecular-orbital (weakly-covalent) component play an important role in association of the [MlXn]m- complexes with the TCP acceptor.

Optimal dimensionality reduction of complex dynamics: The chess game as diffusion on a free-energy landscape

NASA Astrophysics Data System (ADS)

Krivov, Sergei V.

2011-07-01

Dimensionality reduction is ubiquitous in the analysis of complex dynamics. The conventional dimensionality reduction techniques, however, focus on reproducing the underlying configuration space, rather than the dynamics itself. The constructed low-dimensional space does not provide a complete and accurate description of the dynamics. Here I describe how to perform dimensionality reduction while preserving the essential properties of the dynamics. The approach is illustrated by analyzing the chess game—the archetype of complex dynamics. A variable that provides complete and accurate description of chess dynamics is constructed. The winning probability is predicted by describing the game as a random walk on the free-energy landscape associated with the variable. The approach suggests a possible way of obtaining a simple yet accurate description of many important complex phenomena. The analysis of the chess game shows that the approach can quantitatively describe the dynamics of processes where human decision-making plays a central role, e.g., financial and social dynamics.

A novel complex networks clustering algorithm based on the core influence of nodes.

PubMed

Tong, Chao; Niu, Jianwei; Dai, Bin; Xie, Zhongyu

2014-01-01

In complex networks, cluster structure, identified by the heterogeneity of nodes, has become a common and important topological property. Network clustering methods are thus significant for the study of complex networks. Currently, many typical clustering algorithms have some weakness like inaccuracy and slow convergence. In this paper, we propose a clustering algorithm by calculating the core influence of nodes. The clustering process is a simulation of the process of cluster formation in sociology. The algorithm detects the nodes with core influence through their betweenness centrality, and builds the cluster's core structure by discriminant functions. Next, the algorithm gets the final cluster structure after clustering the rest of the nodes in the network by optimizing method. Experiments on different datasets show that the clustering accuracy of this algorithm is superior to the classical clustering algorithm (Fast-Newman algorithm). It clusters faster and plays a positive role in revealing the real cluster structure of complex networks precisely.

Construction of "Toxin Complex" in a Mutant Serotype C Strain of Clostridium botulinum Harboring a Defective Neurotoxin Gene.

PubMed

Suzuki, Tomonori; Nagano, Thomas; Niwa, Koichi; Uchino, Masataka; Tomizawa, Motohiro; Sagane, Yoshimasa; Watanabe, Toshihiro

2017-01-01

A non-toxigenic mutant of the toxigenic serotype C Clostridium botulinum strain Stockholm (C-St), C-N71, does not produce the botulinum neurotoxin (BoNT). However, the original strain C-St produces botulinum toxin complex, in which BoNT is associated with non-toxic non-hemagglutinin (NTNHA) and three hemagglutinin proteins (HA-70, HA-33, and HA-17). Therefore, in this study, we aimed to elucidate the effects of bont gene knockout on the formation of the "toxin complex." Nucleotide sequence analysis revealed that a premature stop codon was introduced in the bont gene, whereas other genes were not affected by this mutation. Moreover, we successfully purified the "toxin complex" produced by C-N71. The "toxin complex" was identified as a mixture of NTNHA/HA-70/HA-17/HA-33 complexes with intact NTNHA or C-terminally truncated NTNHA, without BoNT. These results indicated that knockout of the bont gene does not affect the formation of the "toxin complex." Since the botulinum toxin complex has been shown to play an important role in oral toxin transport in the human and animal body, a non-neurotoxic "toxin complex" of C-N71 may be valuable for the development of an oral drug delivery system.

Motor functions of the basal ganglia.

PubMed

Phillips, J G; Bradshaw, J L; Iansek, R; Chiu, E

1993-01-01

A study of movement disorders such as Parkinson's disease and Huntington's disease can provide an indication of the motor functions of the basal ganglia. Basal-ganglia diseases affect voluntary movement and can cause involuntary movement. Deficits are often manifested during the coordination of fine multi-joint movements (e.g., handwriting). The disturbances of motor control (e.g. akinesia, bradykinesia) caused by basal-ganglia disorders are illustrated. Data suggest that the basal ganglia play an important role in the automatic execution of serially ordered complex movements.

Computer-aided mechanogenesis of skeletal muscle organs from single cells in vitro

NASA Technical Reports Server (NTRS)

Vanderburgh, Herman H.; Swasdison, Somporn; Karlisch, Patricia

1991-01-01

Complex mechanical forces generated in the growing embryo play an important role in organogenesis. Computerized application of similar forces to differentiating skeletal muscle myoblasts in vitro generate three dimensional artificial muscle organs. These organs contain parallel networks of long unbranched myofibers organized into fascicle-like structures. Tendon development is initiated and the muscles are capable of performing directed, functional work. Kinetically engineered organs provide a new method for studying the growth and development of normal and diseased skeletal muscle.

New Developments in the Field of Reaction Technology: The Multiparallel Reactor HPMR 50-96

PubMed Central

Allwardt, Arne; Wendler, Christian; Thurow, Kerstin

2005-01-01

Catalytic high-pressure reactions play an important role in classic bulk chemistry. The optimization of common reactions, the search for new and more effective catalysts, and the increasing use of catalytic pressure reactions in the field of drug development call for high-parallel reaction systems. A crucial task of current developments, apart from the parameters of pressure, temperature, and number of reaction chambers, is, in this respect, the systems' integration into complex laboratory automation environments. PMID:18924722

Computer aided mechanogenesis of skeletal muscle organs from single cells in vitro

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman H.; Swasdison, Somporn; Karlisch, Patricia

1990-01-01

Complex mechanical forces generated in the growing embryo play an important role in organogenesis. Computerized application of similar forces to differentiating skeletal muscle myoblasts in vitro generate three dimensional artificial muscle organs. These organs contain parallel networks of long unbranched myofibers organized into fascicle-like structures. Tendon development is initiated and the muscles are capable of performing directed, functional work. Kinetically engineered organs provide a new method for studying the growth and development of normal and diseased skeletal muscle.

Automatic delineation and 3D visualization of the human ventricular system using probabilistic neural networks

NASA Astrophysics Data System (ADS)

Hatfield, Fraser N.; Dehmeshki, Jamshid

1998-09-01

Neurosurgery is an extremely specialized area of medical practice, requiring many years of training. It has been suggested that virtual reality models of the complex structures within the brain may aid in the training of neurosurgeons as well as playing an important role in the preparation for surgery. This paper focuses on the application of a probabilistic neural network to the automatic segmentation of the ventricles from magnetic resonance images of the brain, and their three dimensional visualization.

Nuclear translocation of proteins and the effect of phosphatidic acid.

PubMed

Yao, Hongyan; Wang, Geliang; Wang, Xuemin

2014-01-01

Transport of proteins containing a nuclear localization signal (NLS) into the nucleus is mediated by nuclear transport receptors called importins, typically dimmers of a cargo-binding α-subunit and a β-subunit that mediates translocation through the nuclear pore complexes (NPCs). However, how proteins without canonical NLS move into the nucleus is not well understood. Recent results indicate that phospholipids, such as phosphatidic acid, play important roles in the intracellular translocation of proteins between the nucleus and cytoplasm.

Nuclear translocation of proteins and the effect of phosphatidic acid

PubMed Central

Yao, Hongyan; Wang, Geliang; Wang, Xuemin

2014-01-01

Transport of proteins containing a nuclear localization signal (NLS) into the nucleus is mediated by nuclear transport receptors called importins, typically dimmers of a cargo-binding α-subunit and a β-subunit that mediates translocation through the nuclear pore complexes (NPCs). However, how proteins without canonical NLS move into the nucleus is not well understood. Recent results indicate that phospholipids, such as phosphatidic acid, play important roles in the intracellular translocation of proteins between the nucleus and cytoplasm. PMID:25482760

Block Oriented Simulation System (BOSS)

NASA Technical Reports Server (NTRS)

Ratcliffe, Jaimie

1988-01-01

Computer simulation is assuming greater importance as a flexible and expedient approach to modeling system and subsystem behavior. Simulation has played a key role in the growth of complex, multiple access space communications such as those used by the space shuttle and the TRW-built Tracking and Data Relay Satellites (TDRS). A powerful new simulator for use in designing and modeling the communication system of NASA's planned Space Station is being developed. Progress to date on the Block (Diagram) Oriented Simulation System (BOSS) is described.

Translational autocontrol of the Escherichia coli hfq RNA chaperone gene.

PubMed

Vecerek, Branislav; Moll, Isabella; Bläsi, Udo

2005-06-01

The conserved bacterial RNA chaperone Hfq has been shown to play an important role in post-transcriptional regulation. Here, we demonstrate that Hfq synthesis is autoregulated at the translational level. We have mapped two Hfq binding sites in the 5'-untranslated region of hfq mRNA and show that Hfq binding inhibits formation of the translation initiation complex. In vitro translation and in vivo studies further revealed that Hfq binding to both sites is required for efficient translational repression of hfq mRNA.

On unified modeling, theory, and method for solving multi-scale global optimization problems

NASA Astrophysics Data System (ADS)

Gao, David Yang

2016-10-01

A unified model is proposed for general optimization problems in multi-scale complex systems. Based on this model and necessary assumptions in physics, the canonical duality theory is presented in a precise way to include traditional duality theories and popular methods as special applications. Two conjectures on NP-hardness are proposed, which should play important roles for correctly understanding and efficiently solving challenging real-world problems. Applications are illustrated for both nonconvex continuous optimization and mixed integer nonlinear programming.

The foundations of the human cultural niche

PubMed Central

Derex, Maxime; Boyd, Robert

2015-01-01

Technological innovations have allowed humans to settle in habitats for which they are poorly suited biologically. However, our understanding of how humans produce complex technologies is limited. We used a computer-based experiment, involving humans and learning bots, to investigate how reasoning abilities, social learning mechanisms and population structure affect the production of virtual artefacts. We found that humans' reasoning abilities play an important role in the production of innovations, but that groups of individuals are able to produce artefacts that are more complex than any isolated individual can produce during the same amount of time. We show that this group-level ability to produce complex innovations is maximized when social information is easy to acquire and when individuals are organized into large and partially connected populations. These results suggest that the transition to behavioural modernity could have been triggered by a change in ancestral between-group interaction patterns. PMID:26400015

Identifying and characterizing key nodes among communities based on electrical-circuit networks.

PubMed

Zhu, Fenghui; Wang, Wenxu; Di, Zengru; Fan, Ying

2014-01-01

Complex networks with community structures are ubiquitous in the real world. Despite many approaches developed for detecting communities, we continue to lack tools for identifying overlapping and bridging nodes that play crucial roles in the interactions and communications among communities in complex networks. Here we develop an algorithm based on the local flow conservation to effectively and efficiently identify and distinguish the two types of nodes. Our method is applicable in both undirected and directed networks without a priori knowledge of the community structure. Our method bypasses the extremely challenging problem of partitioning communities in the presence of overlapping nodes that may belong to multiple communities. Due to the fact that overlapping and bridging nodes are of paramount importance in maintaining the function of many social and biological networks, our tools open new avenues towards understanding and controlling real complex networks with communities accompanied with the key nodes.

Bacterial flagella and Type III secretion: case studies in the evolution of complexity.

PubMed

Pallen, M J; Gophna, U

2007-01-01

Bacterial flagella at first sight appear uniquely sophisticated in structure, so much so that they have even been considered 'irreducibly complex' by the intelligent design movement. However, a more detailed analysis reveals that these remarkable pieces of molecular machinery are the product of processes that are fully compatible with Darwinian evolution. In this chapter we present evidence for such processes, based on a review of experimental studies, molecular phylogeny and microbial genomics. Several processes have played important roles in flagellar evolution: self-assembly of simple repeating subunits, gene duplication with subsequent divergence, recruitment of elements from other systems ('molecular bricolage'), and recombination. We also discuss additional tentative new assignments of homology (FliG with MgtE, FliO with YscJ). In conclusion, rather than providing evidence of intelligent design, flagellar and non-flagellar Type III secretion systems instead provide excellent case studies in the evolution of complex systems from simpler components.

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

The Kto-Skd complex can regulate ptc expression by interacting with Cubitus interruptus (Ci) in the Hedgehog signaling pathway.

PubMed

Mao, Feifei; Yang, Xiaofeng; Fu, Lin; Lv, Xiangdong; Zhang, Zhao; Wu, Wenqing; Yang, Siqi; Zhou, Zhaocai; Zhang, Lei; Zhao, Yun

2014-08-08

The hedgehog (Hh) signaling pathway plays a very important role in metazoan development by controlling pattern formation. Drosophila imaginal discs are subdivided into anterior and posterior compartments that derive from adjacent cell populations. The anterior/posterior (A/P) boundaries, which are critical to maintaining the position of organizers, are established by a complex mechanism involving Hh signaling. Here, we uncover the regulation of ptc in the Hh signaling pathway by two subunits of mediator complex, Kto and Skd, which can also regulate boundary location. Collectively, we provide further evidence that Kto-Skd affects the A/P-axial development of the whole wing disc. Kto can interact with Cubitus interruptus (Ci), bind to the Ci-binding region on ptc promoter, which are both regulated by Hh signals to down-regulate ptc expression. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Polyvinylpyrrolidone-sodium dodecylsulfate complex is a family of pseudo-polyanions with different charge densities: Evidence from capillary electrophoresis, capillary viscosimetry and conductometry.

PubMed

Wu, Yefan; Chen, Jie; Fang, Yun; Zhu, Meng

2016-10-01

Accordance with the previously supposed polyelectrolyte-like behaviour of neutral polymer-anionic surfactant complexes, direct evidence for the formation of the pseudo-polyanions in polyvinylpyrrolidone (PVP)-sodium dodecylsulfate (SDS) solution is put forward in this paper by capillary electrophoresis (CE) experiments in assistance with capillary viscosimetry and conductometry. The contradictory phenomena of the absolute value of relative electrophoretic mobility (re) increasing while the ionization degree (α) decreasing with the increasing specific clusterization [Г] in aqueous PVP-SDS solution are explained by the finding that the PVP-SDS complex is eventually a family of PVP-SDS pseudo-polyanions with different charge densities. And it is found countercations playing an important role in the formation of the PVP-SDS pseudo-polyanions in virtue of bridge effect. Copyright © 2016 Elsevier Inc. All rights reserved.

The Evolution of ICT Markets: An Agent-Based Model on Complex Networks

NASA Astrophysics Data System (ADS)

Zhao, Liangjie; Wu, Bangtao; Chen, Zhong; Li, Li

Information and communication technology (ICT) products exhibit positive network effects.The dynamic process of ICT markets evolution has two intrinsic characteristics: (1) customers are influenced by each others’ purchasing decision; (2) customers are intelligent agents with bounded rationality.Guided by complex systems theory, we construct an agent-based model and simulate on complex networks to examine how the evolution can arise from the interaction of customers, which occur when they make expectations about the future installed base of a product by the fraction of neighbors who are using the same product in his personal network.We demonstrate that network effects play an important role in the evolution of markets share, which make even an inferior product can dominate the whole market.We also find that the intensity of customers’ communication can influence whether the best initial strategy for firms is to improve product quality or expand their installed base.

Synthesis, spectroscopic characterization and structural investigations of a new charge transfer complex of 2,6-diaminopyridine with 3,5-dinitrobenzoic acid: DNA binding and antimicrobial studies

NASA Astrophysics Data System (ADS)

Khan, Ishaat M.; Ahmad, Afaq; Kumar, Sarvendra

2013-03-01

A new charge transfer (CT) complex [(DAPH)+(DNB)-] consisting of 2,6-diaminopyridine (DAP) as donor and 3,5-dinitrobenzoic acid (DNB-H) as acceptor, was synthesized and characterized by FTIR, 1H and 13C NMR, ESI mass spectroscopic and X-ray crystallographic techniques. The hydrogen bonding (N+-H⋯O-) plays an important role to consolidate the cation and anion together. CT complex shows a considerable interaction with Calf thymus DNA. The CT complex was also tested for its antibacterial activity against two Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis and two Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa strains by using Tetracycline as standard, and antifungal property against Aspergillus niger, Candida albicans, and Penicillium sp. by using Nystatin as standard. The results were compared with standard drugs and significant conclusions were obtained. A polymeric net work through H-bonding interactions between neighboring moieties was observed. This has been attributed to the formation of 1:1 type CT complex.

Functional interplay among the flavivirus NS3 protease, helicase, and cofactors.

PubMed

Li, Kuohan; Phoo, Wint Wint; Luo, Dahai

2014-04-01

Flaviviruses are positive-sense RNA viruses, and many are important human pathogens. Nonstructural protein 2B and 3 of the flaviviruses (NS2BNS3) form an endoplasmic reticulum (ER) membrane-associated hetero-dimeric complex through the NS2B transmembrane region. The NS2BNS3 complex is multifunctional. The N-terminal region of NS3, and its cofactor NS2B fold into a protease that is responsible for viral polyprotein processing, and the C-terminal domain of NS3 possesses NTPase/RNA helicase activities and is involved in viral RNA replication and virus particle formation. In addition, NS2BNS3 complex has also been shown to modulate viral pathogenesis and the host immune response. Because of the essential functions that the NS2BNS3 complex plays in the flavivirus life cycle, it is an attractive target for antiviral development. This review focuses on the recent biochemical and structural advances of NS2BNS3 and provides a brief update on the current status of drug development targeting this viral protein complex.

"Synergistic selection": a Darwinian frame for the evolution of complexity.

PubMed

Corning, Peter A; Szathmáry, Eörs

2015-04-21

Non-Darwinian theories about the emergence and evolution of complexity date back at least to Lamarck, and include those of Herbert Spencer and the "emergent evolution" theorists of the later nineteenth and early twentieth centuries. In recent decades, this approach has mostly been espoused by various practitioners in biophysics and complexity theory. However, there is a Darwinian alternative - in essence, an economic theory of complexity - proposing that synergistic effects of various kinds have played an important causal role in the evolution of complexity, especially in the "major transitions". This theory is called the "synergism hypothesis". We posit that otherwise unattainable functional advantages arising from various cooperative phenomena have been favored over time in a dynamic that the late John Maynard Smith characterized and modeled as "synergistic selection". The term highlights the fact that synergistic "wholes" may become interdependent "units" of selection. We provide some historical perspective on this issue, as well as a brief explication of the underlying theory and the concept of synergistic selection, and we describe two relevant models. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Method for Visualization of Incoming Adenovirus Chromatin Complexes in Fixed and Living Cells

PubMed Central

Komatsu, Tetsuro; Dacheux, Denis; Kreppel, Florian; Nagata, Kyosuke; Wodrich, Harald

2015-01-01

Inside the adenovirus virion, the genome forms a chromatin-like structure with viral basic core proteins. Core protein VII is the major DNA binding protein and was shown to remain associated with viral genomes upon virus entry even after nuclear delivery. It has been suggested that protein VII plays a regulatory role in viral gene expression and is a functional component of viral chromatin complexes in host cells. As such, protein VII could be used as a maker to track adenoviral chromatin complexes in vivo. In this study, we characterize a new monoclonal antibody against protein VII that stains incoming viral chromatin complexes following nuclear import. Furthermore, we describe the development of a novel imaging system that uses Template Activating Factor-I (TAF-I/SET), a cellular chromatin protein tightly bound to protein VII upon infection. This setup allows us not only to rapidly visualize protein VII foci in fixed cells but also to monitor their movement in living cells. These powerful tools can provide novel insights into the spatio-temporal regulation of incoming adenoviral chromatin complexes. PMID:26332038

SON and its alternatively spliced isoforms control MLL complex-mediated H3K4me3 and transcription of leukemia-associated genes

PubMed Central

Kim, Jung-Hyun; Baddoo, Melody C.; Park, Eun Young; Stone, Joshua K.; Park, Hyeonsoo; Butler, Thomas W.; Huang, Gang; Yan, Xiaomei; Pauli-Behn, Florencia; Myers, Richard M.; Tan, Ming; Flemington, Erik K.; Lim, Ssang-Taek; Erin Ahn, Eun-Young

2016-01-01

SUMMARY Dysregulation of MLL complex-mediated histone methylation plays a pivotal role in gene expression associated with diseases, but little is known about cellular factors modulating MLL complex activity. Here, we report that SON, previously known as an RNA splicing factor, controls MLL complex-mediated transcriptional initiation. SON binds to DNA near transcription start sites, interacts with menin, and inhibits MLL complex assembly, resulting in decreased H3K4me3 and transcriptional repression. Importantly, alternatively spliced short isoforms of SON are markedly upregulated in acute myeloid leukemia. The short isoforms compete with full-length SON for chromatin occupancy, but lack the menin-binding ability, thereby antagonizing full-length SON function in transcriptional repression while not impairing full-length SON-mediated RNA splicing. Furthermore, overexpression of a short isoform of SON enhances replating potential of hematopoietic progenitors. Our findings define SON as a fine-tuner of the MLL-menin interaction and reveal short SON overexpression as a marker indicating aberrant transcriptional initiation in leukemia. PMID:26990989

WAVE2 Forms a Complex with PKA and Is Involved in PKA Enhancement of Membrane Protrusions*

PubMed Central

Yamashita, Hiroshi; Ueda, Kazumitsu; Kioka, Noriyuki

2011-01-01

PKA contributes to many physiological processes, including glucose homeostasis and cell migration. The substrate specificity of PKA is low compared with other kinases; thus, complex formation with A-kinase-anchoring proteins is important for the localization of PKA in specific subcellular regions and the phosphorylation of specific substrates. Here, we show that PKA forms a complex with WAVE2 (Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2) in MDA-MB-231 breast cancer cells and mouse brain extracts. Two separate regions of WAVE2 are involved in WAVE2-PKA complex formation. This complex localizes to the leading edge of MDA-MB-231 cells. PKA activation results in enlargement of the membrane protrusion. WAVE2 depletion impairs PKA localization at membrane protrusions and the enlargement of membrane protrusion induced by PKA activation. Together, these results suggest that WAVE2 works as an A-kinase-anchoring protein that recruits PKA at membrane protrusions and plays a role in the enlargement of membrane protrusions induced by PKA activation. PMID:21119216

An optimal control framework for dynamic induction control of wind farms and their interaction with the atmospheric boundary layer.

PubMed

Munters, W; Meyers, J

2017-04-13

Complex turbine wake interactions play an important role in overall energy extraction in large wind farms. Current control strategies optimize individual turbine power, and lead to significant energy losses in wind farms compared with lone-standing wind turbines. In recent work, an optimal coordinated control framework was introduced (Goit & Meyers 2015 J. Fluid Mech. 768 , 5-50 (doi:10.1017/jfm.2015.70)). Here, we further elaborate on this framework, quantify the influence of optimization parameters and introduce new simulation results for which gains in power production of up to 21% are observed.This article is part of the themed issue 'Wind energy in complex terrains'. © 2017 The Authors.

Transforming Growth Factor β/Activin signaling in neurons increases susceptibility to starvation.

PubMed

Chng, Wen-Bin Alfred; Koch, Rafael; Li, Xiaoxue; Kondo, Shu; Nagoshi, Emi; Lemaitre, Bruno

2017-01-01

Animals rely on complex signaling network to mobilize its energy stores during starvation. We have previously shown that the sugar-responsive TGFβ/Activin pathway, activated through the TGFβ ligand Dawdle, plays a central role in shaping the post-prandial digestive competence in the Drosophila midgut. Nevertheless, little is known about the TGFβ/Activin signaling in sugar metabolism beyond the midgut. Here, we address the importance of Dawdle (Daw) after carbohydrate ingestion. We found that Daw expression is coupled to dietary glucose through the evolutionarily conserved Mio-Mlx transcriptional complex. In addition, Daw activates the TGFβ/Activin signaling in neuronal populations to regulate triglyceride and glycogen catabolism and energy homeostasis. Loss of those neurons depleted metabolic reserves and rendered flies susceptible to starvation.

Management issues in systems engineering

NASA Astrophysics Data System (ADS)

Shishko, Robert; Chamberlain, Robert G.; Aster, Robert; Bilardo, Vincent; Forsberg, Kevin; Mooz, Hal; Polaski, Lou; Wade, Ron

When applied to a system, the doctrine of successive refinement is a divide-and-conquer strategy. Complex systems are sucessively divided into pieces that are less complex, until they are simple enough to be conquered. This decomposition results in several structures for describing the product system and the producing system. These structures play important roles in systems engineering and project management. Many of the remaining sections in this chapter are devoted to describing some of these key structures. Structures that describe the product system include, but are not limited to, the requirements tree, system architecture and certain symbolic information such as system drawings, schematics, and data bases. The structures that describe the producing system include the project's work breakdown, schedules, cost accounts and organization.

An optimal control framework for dynamic induction control of wind farms and their interaction with the atmospheric boundary layer

PubMed Central

Munters, W.

2017-01-01

Complex turbine wake interactions play an important role in overall energy extraction in large wind farms. Current control strategies optimize individual turbine power, and lead to significant energy losses in wind farms compared with lone-standing wind turbines. In recent work, an optimal coordinated control framework was introduced (Goit & Meyers 2015 J. Fluid Mech. 768, 5–50 (doi:10.1017/jfm.2015.70)). Here, we further elaborate on this framework, quantify the influence of optimization parameters and introduce new simulation results for which gains in power production of up to 21% are observed. This article is part of the themed issue ‘Wind energy in complex terrains’. PMID:28265024

RNA silencing in plant symbiotic bacteria: Insights from a protein-centric view.

PubMed

Jiménez-Zurdo, José I; Robledo, Marta

2017-12-02

Extensive work in model enterobacteria has evidenced that the RNA chaperone Hfq and several endoribonucleases, such as RNase E or RNase III, serve pivotal roles in small RNA-mediated post-transcriptional silencing of gene expression. Characterization of these protein hubs commonly provide global functional and mechanistic insights into complex sRNA regulatory networks. The legume endosymbiont Sinorhizobium meliloti is a non-classical model bacterium with a very complex lifestyle in which riboregulation is expected to play important adaptive functions. Here, we discuss current knowledge about RNA silencing in S. meliloti from the perspective of the activity of Hfq and a recently discovered endoribonuclease (YbeY) exhibiting unprecedented catalytic versatility for the cleavage of single- and double-stranded RNA molecules.

DNA-PK/Ku complex binds to latency-associated nuclear antigen and negatively regulates Kaposi's sarcoma-associated herpesvirus latent replication

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

Cha, Seho; Lim, Chunghun; Lee, Jae Young

2010-04-16

During latent infection, latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays important roles in episomal persistence and replication. Several host factors are associated with KSHV latent replication. Here, we show that the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku70, and Ku86 bind the N-terminal region of LANA. LANA was phosphorylated by DNA-PK and overexpression of Ku70, but not Ku86, impaired transient replication. The efficiency of transient replication was significantly increased in the HCT116 (Ku86 +/-) cell line, compared to the HCT116 (Ku86 +/+) cell line, suggesting that the DNA-PK/Ku complex negatively regulates KSHV latent replication.

Management issues in systems engineering

NASA Technical Reports Server (NTRS)

Shishko, Robert; Chamberlain, Robert G.; Aster, Robert; Bilardo, Vincent; Forsberg, Kevin; Mooz, Hal; Polaski, Lou; Wade, Ron

1993-01-01

When applied to a system, the doctrine of successive refinement is a divide-and-conquer strategy. Complex systems are sucessively divided into pieces that are less complex, until they are simple enough to be conquered. This decomposition results in several structures for describing the product system and the producing system. These structures play important roles in systems engineering and project management. Many of the remaining sections in this chapter are devoted to describing some of these key structures. Structures that describe the product system include, but are not limited to, the requirements tree, system architecture and certain symbolic information such as system drawings, schematics, and data bases. The structures that describe the producing system include the project's work breakdown, schedules, cost accounts and organization.

The Ecology of Role Play: Intentionality and Cultural Evolution

ERIC Educational Resources Information Center

Papadopoulou, Marianna

2012-01-01

This study examines the evolutionary function of children's pretence. The everyday, cultural environment that children engage with is of a highly complex structure. Human adaptation, thus, becomes, by analogy, an equally complex process that requires the development of life skills. Whilst in role play children engage in "mimesis" and…

Use of Child Centered Play Therapy Responses in a Child Care Setting

ERIC Educational Resources Information Center

Muro, Joel H.; Muro, Lilia Lamar; Rose, Katherine Kensinger; Webster, Lindsey; Allen, Cassie

2017-01-01

The communication process between care providers and children can, at times, be complex. Young children typically lack the verbal language necessary for complex emotional expression. In this article, the authors contend that using some basic "child centered play therapy" (CCPT) techniques would be beneficial in enhancing communicative…

Why Are Omics Technologies Important to Understanding the Role of Nutrition in Inflammatory Bowel Diseases?

PubMed Central

Ferguson, Lynnette R.; Barnett, Matthew P. G.

2016-01-01

For many years, there has been confusion about the role that nutrition plays in inflammatory bowel diseases (IBD). It is apparent that good dietary advice for one individual may prove inappropriate for another. As with many diseases, genome-wide association studies across large collaborative groups have been important in revealing the role of genetics in IBD, with more than 200 genes associated with susceptibility to the disease. These associations provide clues to explain the differences in nutrient requirements among individuals. In addition to genes directly involved in the control of inflammation, a number of the associated genes play roles in modulating the gut microbiota. Cell line models enable the generation of hypotheses as to how various bioactive dietary components might be especially beneficial for certain genetic groups. Animal models are necessary to mimic aspects of the complex aetiology of IBD, and provide an important link between tissue culture studies and human trials. Once we are sufficiently confident of our hypotheses, we can then take modified diets to an IBD population that is stratified according to genotype. Studies in IBD patients fed a Mediterranean-style diet have been important in validating our hypotheses and as a proof-of-principle for the application of these sensitive omics technologies to aiding in the control of IBD symptoms. PMID:27775675

An ontology of geo-reasoning to support medical response to attacks with weapons of mass destruction.

PubMed

Kirsh, David; Peterson, Nichole; Lenert, Leslie A

2005-01-01

We study how Metropolitan Medical Response System units conceptualize the physical space of a disaster and their organized response. Using a variety of ethnographic methods before, during, and after a disaster drill, we have developed an initial ontology for geospatial and context-aware technology. The conceptual map of first responders is far more complex than a geographical map. Zones and Areas are used to describe documented concepts critical to MMRS operations. Ad hoc locations also play a critical role, helping first responders communicate tactics in spatial terms. Such distinctions play an important role in the way our experts think about their activity. Successful geoaware alerting systems must incorporate these notions if they are to seamlessly fit into the work flow of first responders.

Multiscale processing of loss of metal: a machine learning approach

NASA Astrophysics Data System (ADS)

De Masi, G.; Gentile, M.; Vichi, R.; Bruschi, R.; Gabetta, G.

2017-07-01

Corrosion is one of the principal causes of degradation to failure of marine structures. In practice, localized corrosion is the most dangerous mode of attack and can result in serious failures, in particular in marine flowlines and inter-field lines, arousing serious concerns relatively to environmental impact. The progress in time of internal corrosion, the location along the route and across the pipe section, the development pattern and the depth of the loss of metal are a very complex issue: the most important factors are products characteristics, transport conditions over the operating lifespan, process fluid-dynamics, and pipeline geometrical configuration. Understanding which factors among them play the most important role is a key step to develop a model able to predict with enough accuracy the sections more exposed to risk of failure. Some factors play a crucial role at certain spatial scales while other factors at other scales. The Mutual Information Theory, intimately related to the concept of Shannon Entropy in Information theory, has been applied to detect the most important variables at each scale. Finally, the variables emerged from this analysis at each scale have been integrated in a predicting data driven model sensibly improving its performance.

Factors affecting variation in mortality of marine Atlantic salmon Salmo salar in Scotland.

PubMed

Soares, Silvia; Murray, Alexander G; Crumlish, Mags; Turnbull, James F; Green, Darren M

2013-03-26

Databases of site production have an important role to play in the investigation and understanding of diseases, since they store valuable amounts of disease and management data. Diseases pose an important constraint to economic expansion of aquaculture. They are dependent on the complex interacting factors of pathogen, environment, and host, and the causes of death can be related to nutritional, environmental, and genetic factors of the host or infectious agents. We examined the drivers of mortality from a single site-production database, which represented one-third of Scottish farmed salmon Salmo salar L. production in 2005, to determine whether mortality 'benchmarking' data could be generalised across sites and production cycles. We show that farm mortality records play an important role in studying mortality losses and identifying of management problems in production. We found that mortalities varied across the months of the year and with the time of year of initial stocking. Production cycles that started in the third quarter of the year had the highest mortality overall. Furthermore, we found site-to-site variation in mortality that may have been caused by either random occurrence of epidemics and environmental events or other local effects.

Manipulation of the Glycan-Specific Natural Antibody Repertoire for Immunotherapy

PubMed Central

New, J. Stewart; King, R. Glenn; Kearney, John F.

2015-01-01

Summary Natural immunoglobulin derived from innate-like B lymphocytes plays important roles in the suppression of inflammatory responses and represents a promising therapeutic target in a growing number of allergic and autoimmune diseases. These antibodies are commonly autoreactive and incorporate evolutionarily conserved specificities, including certain glycan-specific antibodies. Despite this conservation, exposure to bacterial polysaccharides during innate-like B lymphocyte development, through either natural exposure or immunization, induces significant changes in clonal representation within the glycan-reactive B cell pool. Glycan-reactive natural antibodies have been reported to play protective and pathogenic roles in autoimmune and inflammatory diseases. An understanding of the composition and functions of a healthy glycan-reactive natural antibody repertoire is therefore paramount. A more thorough understanding of natural antibody repertoire development holds promise for the design of both biological diagnostics and therapies. In this article we review the development and functions of natural antibodies and examine three glycan specificities, represented in the innate-like B cell pool, to illustrate the complex roles environmental antigens play in natural antibody repertoire development. We also discuss the implications of increased clonal plasticity of the innate-like B cell repertoire during neonatal and perinatal periods, and the prospect of targeting B cell development with interventional therapies and correct defects in this important arm of the adaptive immune system. PMID:26864103

The importance of surface functional groups in the adsorption of copper onto walnut shell derived activated carbon.

PubMed

Xie, Ruzhen; Jin, Yan; Chen, Yao; Jiang, Wenju

2017-12-01

In this study, activated carbon (AC) was prepared from walnut shell using chemical activation. The surface chemistry of the prepared AC was modified by introducing or blocking certain functional groups, and the role of the different functional groups involved in the copper uptake was investigated. The structural and chemical heterogeneity of the produced carbons are characterized by Fourier transform infrared spectrometry, X-ray photoelectron spectroscopy, Boehm titration method and N 2 /77 K adsorption isotherm analysis. The equilibrium and the kinetics of copper adsorption onto AC were studied. The results demonstrated that the functional groups on AC played an important role in copper uptake. Among various surface functional groups, the oxygen-containing group was found to play a critical role in the copper uptake, and oxidation is the most effective way to improve Cu (II) adsorption onto AC. Ion-exchange was identified to be the dominant mechanism in the copper uptake by AC. Some other types of interactions, like complexation, were also proven to be involved in the adsorption process, while physical force was found to play a small role in the copper uptake. The regeneration of copper-loaded AC and the recovery of copper were also studied to evaluate the reusability of the oxidized AC.

The sequential structure of brain activation predicts skill.

PubMed

Anderson, John R; Bothell, Daniel; Fincham, Jon M; Moon, Jungaa

2016-01-29

In an fMRI study, participants were trained to play a complex video game. They were scanned early and then again after substantial practice. While better players showed greater activation in one region (right dorsal striatum) their relative skill was better diagnosed by considering the sequential structure of whole brain activation. Using a cognitive model that played this game, we extracted a characterization of the mental states that are involved in playing a game and the statistical structure of the transitions among these states. There was a strong correspondence between this measure of sequential structure and the skill of different players. Using multi-voxel pattern analysis, it was possible to recognize, with relatively high accuracy, the cognitive states participants were in during particular scans. We used the sequential structure of these activation-recognized states to predict the skill of individual players. These findings indicate that important features about information-processing strategies can be identified from a model-based analysis of the sequential structure of brain activation. Copyright © 2015 Elsevier Ltd. All rights reserved.

New fronts emerge in the influenza cytokine storm.

PubMed

Guo, Xi-Zhi J; Thomas, Paul G

2017-07-01

Influenza virus is a significant pathogen in humans and animals with the ability to cause extensive morbidity and mortality. Exuberant immune responses induced following infection have been described as a "cytokine storm," associated with excessive levels of proinflammatory cytokines and widespread tissue damage. Recent studies have painted a more complex picture of cytokine networks and their contributions to clinical outcomes. While many cytokines clearly inflict immunopathology, others have non-pathological delimited roles in sending alarm signals, facilitating viral clearance, and promoting tissue repair, such as the IL-33-amphiregulin axis, which plays a key role in resolving some types of lung damage. Recent literature suggests that type 2 cytokines, traditionally thought of as not involved in anti-influenza immunity, may play an important regulatory role. Here, we discuss the diverse roles played by cytokines after influenza infection and highlight new, serene features of the cytokine storm, while highlighting the specific functions of relevant cytokines that perform unique immune functions and may have applications for influenza therapy.

Structural basis for binding of aurora-AG198N- INCENP complex: MD simulations and free energy calculations.

PubMed

Tanneeru, Karunakar; Guruprasad, Lalitha

2013-11-01

Aurora-A, B and C are non-receptor serine/threonine kinases in Homo sapiens. In spite of high similarity in their sequences, they possess distinct binding partners. These kinases play an important role in cell division and overexpressed in certain cancers. It has been demonstrated that Gly198 in Aurora-A kinase is responsible for its basal kinase activity, the mutation G198N transforms Aurora-A to Aurora-B like function and localization by binding to Inner centromere protein (INCENP). The molecular mechanisms, structural determinants and the binding energetics of the Aurora-A - INCENP complex owing to a single amino acid G198N mutation are not studied. Therefore, we have docked INCENP into human Aurora-A kinase, mutated Gly198 to Asn, Leu and Ala. The wild type and mutant Aurora-A - INCENP complexes were subjected to 40 ns molecular dynamics (MD) simulations. The Asn198 is located in the amphipathic cavity comprising Leu869(IN), Glu868(IN), Thr872(IN), Tyr197(AurA) and Tyr199(AurA) and the interactions mediated via hydrogen bonds are important to stabilize the Aurora-A(G198N) - INCENP complex. The fluctuations in the secondary structural elements and the solvent accessible surface area of all the four complexes during the MD simulations were studied. We calculated the binding free energy upon mutation in the three mutant complexes. The Aurora-A(G198N) - INCENP complex with hydrophilic amino acid mutation has the negative free energy of solvation indicating favorable interactions with INCENP. Our results provide the structural basis and energetics of the human Aurora-A(G198N) - INCENP complex.

Human T-lymphotropic virus type 1 Tax protein complexes with P-TEFb and competes for Brd4 and 7SK snRNP/HEXIM1 binding.

PubMed

Cho, Won-Kyung; Jang, Moon Kyoo; Huang, Keven; Pise-Masison, Cynthia A; Brady, John N

2010-12-01

Positive transcription elongation factor b (P-TEFb) plays an important role in stimulating RNA polymerase II elongation for viral and cellular gene expression. P-TEFb is found in cells in either an active, low-molecular-weight (LMW) form or an inactive, high-molecular-weight (HMW) form. We report here that human T-lymphotropic virus type 1 (HTLV-1) Tax interacts with the cyclin T1 subunit of P-TEFb, forming a distinct Tax/P-TEFb LMW complex. We demonstrate that Tax can play a role in regulating the amount of HMW complex present in the cell by decreasing the binding of 7SK snRNP/HEXIM1 to P-TEFb. This is seen both in vitro using purified Tax protein and in vivo in cells transduced with Tax expression constructs. Further, we find that a peptide of cyclin T1 spanning the Tax binding domain inhibits the ability of Tax to disrupt HMW P-TEFb complexes. These results suggest that the direct interaction of Tax with cyclin T1 can dissociate P-TEFb from the P-TEFb/7SK snRNP/HEXIM1 complex for activation of the viral long terminal repeat (LTR). We also show that Tax competes with Brd4 for P-TEFb binding. Chromatin immunoprecipitation (ChIP) assays demonstrated that Brd4 and P-TEFb are associated with the basal HTLV-1 LTR, while Tax and P-TEFb are associated with the activated template. Furthermore, the knockdown of Brd4 by small interfering RNA (siRNA) activates the HTLV-1 LTR promoter, which results in an increase in viral expression and production. Our studies have identified Tax as a regulator of P-TEFb that is capable of affecting the balance between its association with the large inactive complex and the small active complex.

Association of Membrane Rafts and Postsynaptic Density: Proteomics, Biochemical, and Ultrastructural Analyses

PubMed Central

Suzuki, Tatsuo; Zhang, Jingping; Miyazawa, Shoko; Liu, Qian; Farzan, Michael R.; Yao, Wei-Dong

2011-01-01

Postsynaptic membrane rafts are believed to play important roles in synaptic signaling, plasticity, and maintenance. However, their molecular identities remain elusive. Further, how they interact with the well-established signaling specialization, the postsynaptic density (PSD), is poorly understood. We previously detected a number of conventional PSD proteins in detergent-resistant membranes (DRMs). Here, we have performed LC-MS/MS (liquid chromatography coupled with tandem mass spectrometry) analyses on postsynaptic membrane rafts and PSDs. Our comparative analysis identified an extensive overlap of protein components in the two structures. This overlapping could be explained, at least partly, by a physical association of the two structures. Meanwhile, a significant number of proteins displayed biased distributions to either rafts or PSDs, suggesting distinct roles for the two postsynaptic specializations. Using biochemical and electron microscopic methods, we directly detected membrane raft-PSD complexes. In vitro reconstitution experiments indicated that the formation of raft-PSD complexes was not due to the artificial reconstruction of once-solubilized membrane components and PSD structures, supporting that these complexes occurred in vivo. Taking together, our results provide evidence that postsynaptic membrane rafts and PSDs may be physically associated. Such association could be important in postsynaptic signal integration, synaptic function, and maintenance. PMID:21797867

“Theory of Food” as a Neurocognitive Adaptation

PubMed Central

Allen, John S.

2011-01-01

Human adult cognition emerges over the course of development via the interaction of multiple critical neurocognitive networks. These networks evolved in response to various selection pressures, many of which were modified or intensified by the intellectual, technological, and socio-cultural environments that arose in connection with the evolution of genus Homo. Networks related to language and theory of mind clearly play an important role in adult cognition. Given the critical importance of food to both basic survival and cultural interaction, a “theory of food” (analogous to theory of mind) may represent another complex network essential for normal cognition. I propose that theory of food evolved as an internal, cognitive representation of our diets in our minds. Like other complex cognitive abilities, it relies on complex and overlapping dedicated neural networks that develop in childhood under familial and cultural influences. Normative diets are analogous to first languages in that they are acquired without overt teaching; they are also difficult to change or modify once a critical period in development is passed. Theory of food suggests that cognitive activities related to food may be cognitive enhancers, which could have implications for maintaining healthy brain function in aging. PMID:22262561

RNF168 forms a functional complex with RAD6 during the DNA damage response

PubMed Central

Liu, Chao; Wang, Degui; Wu, Jiaxue; Keller, Jennifer; Ma, Teng; Yu, Xiaochun

2013-01-01

Summary Protein ubiquitination plays an important role in initiating the DNA damage response. Following DNA damage, E2 ubiquitin conjugating enzymes are crucial for catalyzing substrate ubiquitination that recruits downstream DNA repair factors to DNA lesions. To identify novel E2 conjugating enzymes important for initiating the DNA-damage-induced ubiquitination cascade, we screened most of the known E2 enzymes and found that RAD6A and RAD6B function together with RNF168 in the ionizing radiation (IR)-induced DNA damage response. Similarly to RNF168-deficient cells, RAD6A- or RAD6B-deficient cells exhibit a reduction in DNA-damage-induced protein ubiquitination. Correspondingly, DNA-damage-induced foci formation of DNA damage repair proteins, such as BRCA1 and 53BP1, is impaired in the absence of RAD6A or RAD6B. Moreover, the RNF168–RAD6 complex targeted histone H1.2 for ubiquitination in vitro and regulated DNA-damage-induced histone H1.2 ubiquitination in vivo. Collectively, these data demonstrate that RNF168, in complex with RAD6A or RAD6B, is activated in the DNA-damage-induced protein ubiquitination cascade. PMID:23525009

The Complex Structure of Receptive Fields in the Middle Temporal Area

PubMed Central

Richert, Micah; Albright, Thomas D.; Krekelberg, Bart

2012-01-01

Neurons in the middle temporal area (MT) are often viewed as motion detectors that prefer a single direction of motion in a single region of space. This assumption plays an important role in our understanding of visual processing, and models of motion processing in particular. We used extracellular recordings in area MT of awake, behaving monkeys (M. mulatta) to test this assumption with a novel reverse correlation approach. Nearly half of the MT neurons in our sample deviated significantly from the classical view. First, in many cells, direction preference changed with the location of the stimulus within the receptive field. Second, the spatial response profile often had multiple peaks with apparent gaps in between. This shows that visual motion analysis in MT has access to motion detectors that are more complex than commonly thought. This complexity could be a mere byproduct of imperfect development, but can also be understood as the natural consequence of the non-linear, recurrent interactions among laterally connected MT neurons. An important direction for future research is to investigate whether these in homogeneities are advantageous, how they can be incorporated into models of motion detection, and whether they can provide quantitative insight into the underlying effective connectivity. PMID:23508640

"Theory of food" as a neurocognitive adaptation.

PubMed

Allen, John S

2012-01-01

Human adult cognition emerges over the course of development via the interaction of multiple critical neurocognitive networks. These networks evolved in response to various selection pressures, many of which were modified or intensified by the intellectual, technological, and sociocultural environments that arose in connection with the evolution of genus Homo. Networks related to language and theory of mind clearly play an important role in adult cognition. Given the critical importance of food to both basic survival and cultural interaction, a "theory of food" (analogous to theory of mind) may represent another complex network essential for normal cognition. I propose that theory of food evolved as an internal, cognitive representation of our diets in our minds. Like other complex cognitive abilities, it relies on complex and overlapping dedicated neural networks that develop in childhood under familial and cultural influences. Normative diets are analogous to first languages in that they are acquired without overt teaching; they are also difficult to change or modify once a critical period in development is passed. Theory of food suggests that cognitive activities related to food may be cognitive enhancers, which could have implications for maintaining healthy brain function in aging. Copyright © 2012 Wiley Periodicals, Inc.

NUCLEAR FACTOR Y Transcription Factors Have Both Opposing and Additive Roles in ABA-Mediated Seed Germination

PubMed Central

Kumimoto, Roderick W.; Siriwardana, Chamindika L.; Gayler, Krystal K.; Risinger, Jan R.; Siefers, Nicholas; Holt, Ben F.

2013-01-01

In the model organism Arabidopsis thaliana the heterotrimeric transcription factor NUCLEAR FACTOR Y (NF-Y) has been shown to play multiple roles in facilitating plant growth and development. Although NF-Y itself represents a multi-protein transcriptional complex, recent studies have shown important interactions with other transcription factors, especially those in the bZIP family. Here we add to the growing evidence that NF-Y and bZIP form common complexes to affect many processes. We carried out transcriptional profiling on nf-yc mutants and through subsequent analyses found an enrichment of bZIP binding sites in the promoter elements of misregulated genes. Using NF-Y as bait, yeast two hybrid assays yielded interactions with bZIP proteins that are known to control ABA signaling. Accordingly, we find that plants mutant for several NF-Y subunits show characteristic phenotypes associated with the disruption of ABA signaling. While previous reports have shown additive roles for NF-YC family members in photoperiodic flowering, we found that they can have opposing roles in ABA signaling. Collectively, these results demonstrated the importance and complexity of NF-Y in the integration of environmental and hormone signals. PMID:23527203

Control of complex networks requires both structure and dynamics

NASA Astrophysics Data System (ADS)

Gates, Alexander J.; Rocha, Luis M.

2016-04-01

The study of network structure has uncovered signatures of the organization of complex systems. However, there is also a need to understand how to control them; for example, identifying strategies to revert a diseased cell to a healthy state, or a mature cell to a pluripotent state. Two recent methodologies suggest that the controllability of complex systems can be predicted solely from the graph of interactions between variables, without considering their dynamics: structural controllability and minimum dominating sets. We demonstrate that such structure-only methods fail to characterize controllability when dynamics are introduced. We study Boolean network ensembles of network motifs as well as three models of biochemical regulation: the segment polarity network in Drosophila melanogaster, the cell cycle of budding yeast Saccharomyces cerevisiae, and the floral organ arrangement in Arabidopsis thaliana. We demonstrate that structure-only methods both undershoot and overshoot the number and which sets of critical variables best control the dynamics of these models, highlighting the importance of the actual system dynamics in determining control. Our analysis further shows that the logic of automata transition functions, namely how canalizing they are, plays an important role in the extent to which structure predicts dynamics.

Identification of human Phosphatidyl Inositol 5-Phosphate 4-Kinase as an RNA binding protein that is imported into Plasmodium falciparum.

PubMed

Vindu, Arya; Dandewad, Vishal; Seshadri, Vasudevan

2018-04-06

Plasmodium falciparum is a causative agent for malaria and has a complex life cycle in human and mosquito hosts. Translation repression of specific set of mRNA has been reported in gametocyte stages of this parasite. A conserved element present in the 3'UTR of some of these transcripts was identified. Biochemical studies have identified components of the RNA storage and/or translation inhibitor complex but it is not yet clear how the complex is specifically recruited on the RNA targeted for translation regulation. We used the 3'UTR region of translationally regulated transcripts to identify Phosphatidyl-inositol 5-phosphate 4-kinase (PIP4K2A) as the protein that associates with these RNAs. We further show that recombinant PIP4K2A has the RNA binding activity and can associate specifically with Plasmodium 3'UTR RNAs. Immunostainings show that hPIP4K2A is imported into the Plasmodium parasite from RBC. These results identify a novel RNA binding role for PIP4K2A that may play a role in Plasmodium propagation. Copyright © 2018 Elsevier Inc. All rights reserved.

Omics/systems biology and cancer cachexia.

PubMed

Gallagher, Iain J; Jacobi, Carsten; Tardif, Nicolas; Rooyackers, Olav; Fearon, Kenneth

2016-06-01

Cancer cachexia is a complex syndrome generated by interaction between the host and tumour cells with a background of treatment effects and toxicity. The complexity of the physiological pathways likely involved in cancer cachexia necessitates a holistic view of the relevant biology. Emergent properties are characteristic of complex systems with the result that the end result is more than the sum of its parts. Recognition of the importance of emergent properties in biology led to the concept of systems biology wherein a holistic approach is taken to the biology at hand. Systems biology approaches will therefore play an important role in work to uncover key mechanisms with therapeutic potential in cancer cachexia. The 'omics' technologies provide a global view of biological systems. Genomics, transcriptomics, proteomics, lipidomics and metabolomics approaches all have application in the study of cancer cachexia to generate systems level models of the behaviour of this syndrome. The current work reviews recent applications of these technologies to muscle atrophy in general and cancer cachexia in particular with a view to progress towards integration of these approaches to better understand the pathology and potential treatment pathways in cancer cachexia. Copyright © 2016. Published by Elsevier Ltd.

The MCM-associated protein MCM-BP is important for human nuclear morphology.

PubMed

Jagannathan, Madhav; Sakwe, Amos M; Nguyen, Tin; Frappier, Lori

2012-01-01

Mini-chromosome maintenance complex-binding protein (MCM-BP) was discovered as a protein that is strongly associated with human MCM proteins, known to be crucial for DNA replication in providing DNA helicase activity. The Xenopus MCM-BP homologue appears to play a role in unloading MCM complexes from chromatin after DNA synthesis; however, the importance of MCM-BP and its functional contribution to human cells has been unclear. Here we show that depletion of MCM-BP by sustained expression of short hairpin RNA (shRNA) results in highly abnormal nuclear morphology and centrosome amplification. The abnormal nuclear morphology was not seen with depletion of other MCM proteins and was rescued with shRNA-resistant MCM-BP. MCM-BP depletion was also found to result in transient activation of the G2 checkpoint, slowed progression through G2 and increased replication protein A foci, indicative of replication stress. In addition, MCM-BP depletion led to increased cellular levels of MCM proteins throughout the cell cycle including soluble MCM pools. The results suggest that MCM-BP makes multiple contributions to human cells that are not limited to unloading of the MCM complex.

Convergent microRNA actions coordinate neocortical development.

PubMed

Barca-Mayo, Olga; De Pietri Tonelli, Davide

2014-08-01

Neocortical development is a complex process that, at the cellular level, involves tight control of self-renewal, cell fate commitment, survival, differentiation and delamination/migration. These processes require, at the molecular level, the precise regulation of intrinsic signaling pathways and extrinsic factors with coordinated action in a spatially and temporally specific manner. Transcriptional regulation plays an important role during corticogenesis; however, microRNAs (miRNAs) are emerging as important post-transcriptional regulators of various aspects of central nervous system development. miRNAs are a class of small, single-stranded noncoding RNA molecules that control the expression of the majority of protein coding genes (i.e., targets). How do different miRNAs achieve precise control of gene networks during neocortical development? Here, we critically review all the miRNA-target interactions validated in vivo, with relevance to the generation and migration of pyramidal-projection glutamatergic neurons, and for the initial formation of cortical layers in the embryonic development of rodent neocortex. In particular, we focus on convergent miRNA actions, which are still a poorly understood layer of complexity in miRNA signaling, but potentially one of the keys to disclosing how miRNAs achieve the precise coordination of complex biological processes such as neocortical development.

The Not4 E3 Ligase and CCR4 Deadenylase Play Distinct Roles in Protein Quality Control

PubMed Central

Halter, David; Collart, Martine A.; Panasenko, Olesya O.

2014-01-01

Eukaryotic cells control their proteome by regulating protein production and protein clearance. Protein production is determined to a large extent by mRNA levels, whereas protein degradation depends mostly upon the proteasome. Dysfunction of the proteasome leads to the accumulation of non-functional proteins that can aggregate, be toxic for the cell, and, in extreme cases, lead to cell death. mRNA levels are controlled by their rates of synthesis and degradation. Recent evidence indicates that these rates have oppositely co-evolved to ensure appropriate mRNA levels. This opposite co-evolution has been correlated with the mutations in the Ccr4-Not complex. Consistently, the deadenylation enzymes responsible for the rate-limiting step in eukaryotic mRNA degradation, Caf1 and Ccr4, are subunits of the Ccr4-Not complex. Another subunit of this complex is a RING E3 ligase, Not4. It is essential for cellular protein solubility and has been proposed to be involved in co-translational quality control. An open question has been whether this role of Not4 resides strictly in the regulation of the deadenylation module of the Ccr4-Not complex. However, Not4 is important for proper assembly of the proteasome, and the Ccr4-Not complex may have multiple functional modules that participate in protein quality control in different ways. In this work we studied how the functions of the Caf1/Ccr4 and Not4 modules are connected. We concluded that Not4 plays a role in protein quality control independently of the Ccr4 deadenylase, and that it is involved in clearance of aberrant proteins at least in part via the proteasome. PMID:24465968

A new mathematical modeling for pure parsimony haplotyping problem.

PubMed

Feizabadi, R; Bagherian, M; Vaziri, H R; Salahi, M

2016-11-01

Pure parsimony haplotyping (PPH) problem is important in bioinformatics because rational haplotyping inference plays important roles in analysis of genetic data, mapping complex genetic diseases such as Alzheimer's disease, heart disorders and etc. Haplotypes and genotypes are m-length sequences. Although several integer programing models have already been presented for PPH problem, its NP-hardness characteristic resulted in ineffectiveness of those models facing the real instances especially instances with many heterozygous sites. In this paper, we assign a corresponding number to each haplotype and genotype and based on those numbers, we set a mixed integer programing model. Using numbers, instead of sequences, would lead to less complexity of the new model in comparison with previous models in a way that there are neither constraints nor variables corresponding to heterozygous nucleotide sites in it. Experimental results approve the efficiency of the new model in producing better solution in comparison to two state-of-the art haplotyping approaches. Copyright © 2016 Elsevier Inc. All rights reserved.

D1 receptors physically interact with N-type calcium channels to regulate channel distribution and dendritic calcium entry.

PubMed

Kisilevsky, Alexandra E; Mulligan, Sean J; Altier, Christophe; Iftinca, Mircea C; Varela, Diego; Tai, Chao; Chen, Lina; Hameed, Shahid; Hamid, Jawed; Macvicar, Brian A; Zamponi, Gerald W

2008-05-22

Dopamine signaling through D1 receptors in the prefrontal cortex (PFC) plays a critical role in the maintenance of higher cognitive functions, such as working memory. At the cellular level, these functions are predicated to involve alterations in neuronal calcium levels. The dendrites of PFC neurons express D1 receptors and N-type calcium channels, yet little information exists regarding their coupling. Here, we show that D1 receptors potently inhibit N-type channels in dendrites of rat PFC neurons. Using coimmunoprecipitation, we demonstrate the existence of a D1 receptor-N-type channel signaling complex in this region, and we provide evidence for a direct receptor-channel interaction. Finally, we demonstrate the importance of this complex to receptor-channel colocalization in heterologous systems and in PFC neurons. Our data indicate that the N-type calcium channel is an important physiological target of D1 receptors and reveal a mechanism for D1 receptor-mediated regulation of cognitive function in the PFC.

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

Alí-Torres, Jorge; Mirats, Andrea; Maréchal, Jean-Didier

Amyloid plaques formation and oxidative stress are two key events in the pathology of the Alzheimer disease (AD), in which metal cations have been shown to play an important role. In particular, the interaction of the redox active Cu{sup 2+} metal cation with Aβ has been found to interfere in amyloid aggregation and to lead to reactive oxygen species (ROS). A detailed knowledge of the electronic and molecular structure of Cu{sup 2+}-Aβ complexes is thus important to get a better understanding of the role of these complexes in the development and progression of the AD disease. The computational treatment ofmore » these systems requires a combination of several available computational methodologies, because two fundamental aspects have to be addressed: the metal coordination sphere and the conformation adopted by the peptide upon copper binding. In this paper we review the main computational strategies used to deal with the Cu{sup 2+}-Aβ coordination and build plausible Cu{sup 2+}-Aβ models that will afterwards allow determining physicochemical properties of interest, such as their redox potential.« less

Interaction of cinnamic acid and methyl cinnamate with bovine serum albumin: A thermodynamic approach.

PubMed

Nunes, Natália Moreira; Pacheco, Ana Flávia Coelho; Agudelo, Álvaro Javier Patiño; da Silva, Luis Henrique Mendes; Pinto, Maximiliano Soares; Hespanhol, Maria do Carmo; Pires, Ana Clarissa Dos Santos

2017-12-15

Cinnamic acid (CA) and methyl cinnamate (MC) have attracted interest of researchers because of their broad therapeutic functions. Here, we investigated the interaction of CA and MC with bovine serum albumin (BSA) at pH 3.5, 5.0, and 7.4 using fluorescence spectroscopy, differential scanning nanocalorimetry, and measurements of interfacial tension, size, and zeta potential. BSA formed a complex with the ligands with stoichiometry of approximately 1.0. At pH 7.4, CA-BSA complex formation was entropically driven. The interaction between MC and BSA was more favorable than with CA and was enthalpically driven under the same conditions. The pH played an important role in BSA conformation, which altered the manner in which it interacts with the ligands. Interestingly, both CA and MC had no effect on the surface tension of BSA/air interfaces. These data contribute to the knowledge of CA/MC-BSA interactions and provide important data for application in the food industry. Copyright © 2017 Elsevier Ltd. All rights reserved.

Determination of dopamine in pharmaceutical formulation using enhanced luminescence from europium complex

NASA Astrophysics Data System (ADS)

Wabaidur, Saikh Mohammad; ALOthman, Zeid Abdullah; Naushad, Mu.

Biologically important compound dopamine plays an important role in the central and peripheral nervous systems. Insufficient dopamine level due to the loss of dopamine producing cells may lead to disease called Schizophrenia and Parkinson's disease. Hence, a simple and fast detection of dopamine is necessary to study in the fields of neurophysiology and clinical medicine. An enhanced fluorimetric determination of dopamine in the presence of ascorbic acid is achieved using photoluminescence of europium complex, Eu(III)-dipicolinic acid. In order to obtain better responses, several operational parameters have been investigated. Under the optimum conditions, the method showed good stability and reproducibility. The application of this method for the determination of dopamine neurotransmitters was satisfactory. Linear response was found down to 3.0 × 10-7 M with limit of detection 1.0 × 10-8 M. The relative standard deviation was found to be 3.33% from 20 independent measurements for 1.0 × 10-5 M of dopamine.

Analytical close-form solutions to the elastic fields of solids with dislocations and surface stress

NASA Astrophysics Data System (ADS)

Ye, Wei; Paliwal, Bhasker; Ougazzaden, Abdallah; Cherkaoui, Mohammed

2013-07-01

The concept of eigenstrain is adopted to derive a general analytical framework to solve the elastic field for 3D anisotropic solids with general defects by considering the surface stress. The formulation shows the elastic constants and geometrical features of the surface play an important role in determining the elastic fields of the solid. As an application, the analytical close-form solutions to the stress fields of an infinite isotropic circular nanowire are obtained. The stress fields are compared with the classical solutions and those of complex variable method. The stress fields from this work demonstrate the impact from the surface stress when the size of the nanowire shrinks but becomes negligible in macroscopic scale. Compared with the power series solutions of complex variable method, the analytical solutions in this work provide a better platform and they are more flexible in various applications. More importantly, the proposed analytical framework profoundly improves the studies of general 3D anisotropic materials with surface effects.

STERILE APETALA modulates the stability of a repressor protein complex to control organ size in Arabidopsis thaliana

PubMed Central

Wang, Zhibiao; Ru, Licong; Baekelandt, Alexandra; Goossens, Alain; Xu, Ran; Zhu, Zhengge; Inzé, Dirk; Li, Yunhai

2018-01-01

Organ size control is of particular importance for developmental biology and agriculture, but the mechanisms underlying organ size regulation remain elusive in plants. Meristemoids, which possess stem cell-like properties, have been recognized to play important roles in leaf growth. We have recently reported that the Arabidopsis F-box protein STERILE APETALA (SAP)/SUPPRESSOR OF DA1 (SOD3) promotes meristemoid proliferation and regulates organ size by influencing the stability of the transcriptional regulators PEAPODs (PPDs). Here we demonstrate that KIX8 and KIX9, which function as adaptors for the corepressor TOPLESS and PPD, are novel substrates of SAP. SAP interacts with KIX8/9 and modulates their protein stability. Further results show that SAP acts in a common pathway with KIX8/9 and PPD to control organ growth by regulating meristemoid cell proliferation. Thus, these findings reveal a molecular mechanism by which SAP targets the KIX-PPD repressor complex for degradation to regulate meristemoid cell proliferation and organ size. PMID:29401459

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

Pan, Ronghui; Satkovich, John; Hu, Jianping

Peroxisomes are ubiquitous eukaryotic organelles that play pivotal roles in a suite of metabolic processes and often act coordinately with other organelles, such as chloroplasts and mitochondria. Peroxisomes import proteins to the peroxisome matrix by peroxins (PEX proteins), but how the function of the PEX proteins is regulated is poorly understood. In this study, we identified the Arabidopsis RING (really interesting new gene) type E3 ubiquitin ligase SP1 [suppressor of plastid protein import locus 1 (ppi1) 1] as a peroxisome membrane protein with a regulatory role in peroxisome protein import. SP1 interacts physically with the two components of the peroxisomemore » protein docking complex PEX13–PEX14 and the (RING)-finger peroxin PEX2. Loss of SP1 function suppresses defects of the pex14-2 and pex13-1 mutants, and SP1 is involved in the degradation of PEX13 and possibly PEX14 and all three RING peroxins. An in vivo ubiquitination assay showed that SP1 has the ability to promote PEX13 ubiquitination. Our study has revealed that, in addition to its previously reported function in chloroplast biogenesis, SP1 plays a role in peroxisome biogenesis. The same E3 ubiquitin ligase promotes the destabilization of components of two distinct protein-import machineries, indicating that degradation of organelle biogenesis factors by the ubiquitin–proteasome system may constitute an important regulatory mechanism in coordinating the biogenesis of metabolically linked organelles in eukaryotes.« less

Thiolate-bridged dinuclear ruthenium and iron complexes as robust and efficient catalysts toward oxidation of molecular dihydrogen in protic solvents.

PubMed

Yuki, Masahiro; Sakata, Ken; Hirao, Yoshifumi; Nonoyama, Nobuaki; Nakajima, Kazunari; Nishibayashi, Yoshiaki

2015-04-01

Thiolate-bridged dinuclear ruthenium and iron complexes are found to work as efficient catalysts toward oxidation of molecular dihydrogen in protic solvents such as water and methanol under ambient reaction conditions. Heterolytic cleavage of the coordinated molecular dihydrogen at the dinuclear complexes and the sequential oxidation of the produced hydride complexes are involved as key steps to promote the present catalytic reaction. The catalytic activity of the dinuclear complexes toward the chemical oxidation of molecular dihydrogen achieves up to 10000 TON (turnover number), and electrooxidation of molecular dihydrogen proceeds quite rapidly. The result of the density functional theory (DFT) calculation on the reaction pathway indicates that a synergistic effect between the two ruthenium atoms plays an important role to realize the catalytic oxidation of molecular dihydrogen efficiently. The present dinuclear ruthenium complex is found to work as an efficient organometallic anode catalyst for the fuel cell. It is noteworthy that the present dinuclear complex worked not only as an effective catalyst toward chemical and electrochemical oxidation of molecular dihydrogen but also as a good anode catalyst for the fuel cell. We consider that the result described in this paper provides useful and valuable information to develop highly efficient and low-cost transition metal complexes as anode catalysts in the fuel cell.

Structure and Function of p97 and Pex1/6 Type II AAA+ Complexes.

PubMed

Saffert, Paul; Enenkel, Cordula; Wendler, Petra

2017-01-01

Protein complexes of the Type II AAA+ (ATPases associated with diverse cellular activities) family are typically hexamers of 80-150 kDa protomers that harbor two AAA+ ATPase domains. They form double ring assemblies flanked by associated domains, which can be N-terminal, intercalated or C-terminal to the ATPase domains. Most prominent members of this family include NSF (N-ethyl-maleimide sensitive factor), p97/VCP (valosin-containing protein), the Pex1/Pex6 complex and Hsp104 in eukaryotes and ClpB in bacteria. Tremendous efforts have been undertaken to understand the conformational dynamics of protein remodeling type II AAA+ complexes. A uniform mode of action has not been derived from these works. This review focuses on p97/VCP and the Pex1/6 complex, which both structurally remodel ubiquitinated substrate proteins. P97/VCP plays a role in many processes, including ER- associated protein degradation, and the Pex1/Pex6 complex dislocates and recycles the transport receptor Pex5 from the peroxisomal membrane during peroxisomal protein import. We give an introduction into existing knowledge about the biochemical and cellular activities of the complexes before discussing structural information. We particularly emphasize recent electron microscopy structures of the two AAA+ complexes and summarize their structural differences.

Complex Dynamics of the Power Transmission Grid (and other Critical Infrastructures)

NASA Astrophysics Data System (ADS)

Newman, David

2015-03-01

Our modern societies depend crucially on a web of complex critical infrastructures such as power transmission networks, communication systems, transportation networks and many others. These infrastructure systems display a great number of the characteristic properties of complex systems. Important among these characteristics, they exhibit infrequent large cascading failures that often obey a power law distribution in their probability versus size. This power law behavior suggests that conventional risk analysis does not apply to these systems. It is thought that much of this behavior comes from the dynamical evolution of the system as it ages, is repaired, upgraded, and as the operational rules evolve with human decision making playing an important role in the dynamics. In this talk, infrastructure systems as complex dynamical systems will be introduced and some of their properties explored. The majority of the talk will then be focused on the electric power transmission grid though many of the results can be easily applied to other infrastructures. General properties of the grid will be discussed and results from a dynamical complex systems power transmission model will be compared with real world data. Then we will look at a variety of uses of this type of model. As examples, we will discuss the impact of size and network homogeneity on the grid robustness, the change in risk of failure as generation mix (more distributed vs centralized for example) changes, as well as the effect of operational changes such as the changing the operational risk aversion or grid upgrade strategies. One of the important outcomes from this work is the realization that ``improvements'' in the system components and operational efficiency do not always improve the system robustness, and can in fact greatly increase the risk, when measured as a risk of large failure.

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

Guo, Zheng; Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Dadao Bei, Guangzhou 510515; Zhou, Yuning

Highlights: Black-Right-Pointing-Pointer Rictor associates with FBXW7 to form an E3 complex. Black-Right-Pointing-Pointer Knockdown of rictor decreases ubiquitination of c-Myc and cylin E. Black-Right-Pointing-Pointer Knockdown of rictor increases protein levels of c-Myc and cylin E. Black-Right-Pointing-Pointer Overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. Black-Right-Pointing-Pointer Rictor regulation of c-Myc and cyclin E requires FBXW7. -- Abstract: Rictor (Rapamycin-insensitive companion of mTOR) forms a complex with mTOR and phosphorylates and activates Akt. Activation of Akt induces expression of c-Myc and cyclin E, which are overexpressed in colorectal cancer and play an important role in colorectal cancer cell proliferation.more » Here, we show that rictor associates with FBXW7 to form an E3 complex participating in the regulation of c-Myc and cyclin E degradation. The Rictor-FBXW7 complex is biochemically distinct from the previously reported mTORC2 and can be immunoprecipitated independently of mTORC2. Moreover, knocking down of rictor in serum-deprived colorectal cancer cells results in the decreased ubiquitination and increased protein levels of c-Myc and cyclin E while overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. Genetic knockout of FBXW7 blunts the effects of rictor, suggesting that rictor regulation of c-Myc and cyclin E requires FBXW7. Our findings identify rictor as an important component of FBXW7 E3 ligase complex participating in the regulation of c-Myc and cyclin E protein ubiquitination and degradation. Importantly, our results suggest that elevated growth factor signaling may contribute to decrease rictor/FBXW7-mediated ubiquitination of c-Myc and cyclin E, thus leading to accumulation of cyclin E and c-Myc in colorectal cancer cells.« less

Modulation of Intestinal Paracellular Transport by Bacterial Pathogens.

PubMed

Roxas, Jennifer Lising; Viswanathan, V K

2018-03-25

The passive and regulated movement of ions, solutes, and water via spaces between cells of the epithelial monolayer plays a critical role in the normal intestinal functioning. This paracellular pathway displays a high level of structural and functional specialization, with the membrane-spanning complexes of the tight junctions, adherens junctions, and desmosomes ensuring its integrity. Tight junction proteins, like occludin, tricellulin, and the claudin family isoforms, play prominent roles as barriers to unrestricted paracellular transport. The past decade has witnessed major advances in our understanding of the architecture and function of epithelial tight junctions. While it has been long appreciated that microbes, notably bacterial and viral pathogens, target and disrupt junctional complexes and alter paracellular permeability, the precise mechanisms remain to be defined. Notably, renewed efforts will be required to interpret the available data on pathogen-mediated barrier disruption in the context of the most recent findings on tight junction structure and function. While much of the focus has been on pathogen-induced dysregulation of junctional complexes, commensal microbiota and their products may influence paracellular permeability and contribute to the normal physiology of the gut. Finally, microbes and their products have become important tools in exploring host systems, including the junctional properties of epithelial cells. © 2018 American Physiological Society. Compr Physiol 8:823-842, 2018. Copyright © 2018 American Physiological Society. All rights reserved.

The role of metals in protein conformational disorders - The case of prion protein and Aβ -peptide

NASA Astrophysics Data System (ADS)

De Santis, E.; Minicozzi, V.; Morante, S.; Rossi, G. C.; Stellato, F.

2016-02-01

Protein conformational disorders are members of a vast class of pathologies in which endogenous proteins or peptides undergo a misfolding process by switching from the physiological soluble configuration to a pathological fibrillar insoluble state. An important, but not yet fully elucidated, role in the process appears to be played by transition metal ions, mainly copper and zinc. X-ray absorption spectroscopy is one of the most suitable techniques for the structural characterization of biological molecules in complex with metal. Owing to its chemical selectivity and sensitivity to the local atomic geometry around the absorber, it can be successfully used to study the environment of metal ions in complex with proteins and peptides in physiological conditions. In this paper we present X-ray absorption spectroscopy studies of the metal ions coordination modes in systems where metals are complexed with specific amyloidogenic proteins and peptides. In particular, we show results concerning the Amyloid β peptide, that is involved in Alzheimer's disease, and the Prion protein, that is responsible for the Transmissible Spongiform Encephalopathy. Our findings suggest that the copper and zinc ions may play a crucial role in the aggregation and fibril formation process of these two biomolecules. Elucidating this kind of interaction could be a key preliminary step before any viable therapy can be conceived or designed.

Isolation of integrin-based adhesion complexes.

PubMed

Jones, Matthew C; Humphries, Jonathan D; Byron, Adam; Millon-Frémillon, Angélique; Robertson, Joseph; Paul, Nikki R; Ng, Daniel H J; Askari, Janet A; Humphries, Martin J

2015-03-02

The integration of cells with their extracellular environment is facilitated by cell surface adhesion receptors, such as integrins, which play important roles in both normal development and the onset of pathologies. Engagement of integrins with their ligands in the extracellular matrix, or counter-receptors on other cells, initiates the intracellular assembly of a wide variety of proteins into adhesion complexes such as focal contacts, focal adhesions, and fibrillar adhesions. The proteins recruited to these complexes mediate bidirectional signaling across the plasma membrane, and, as such, help to coordinate and/or modulate the multitude of physical and chemical signals to which the cell is subjected. The protocols in this unit describe two approaches for the isolation or enrichment of proteins contained within integrin-associated adhesion complexes, together with their local plasma membrane/cytosolic environments, from cells in culture. In the first protocol, integrin-associated adhesion structures are affinity isolated using microbeads coated with extracellular ligands or antibodies. The second protocol describes the isolation of ventral membrane preparations that are enriched for adhesion complex structures. The protocols permit the determination of adhesion complex components via subsequent downstream analysis by western blotting or mass spectrometry. Copyright © 2015 John Wiley & Sons, Inc.

A Novel Mammalian Complex Containing Sin3B Mitigates Histone Acetylation and RNA Polymerase II Progression within Transcribed Loci▿

PubMed Central

Jelinic, Petar; Pellegrino, Jessica; David, Gregory

2011-01-01

Transcription requires the progression of RNA polymerase II (RNAP II) through a permissive chromatin structure. Recent studies of Saccharomyces cerevisiae have demonstrated that the yeast Sin3 protein contributes to the restoration of the repressed chromatin structure at actively transcribed loci. Yet, the mechanisms underlying the restoration of the repressive chromatin structure at transcribed loci and its significance in gene expression have not been investigated in mammals. We report here the identification of a mammalian complex containing the corepressor Sin3B, the histone deacetylase HDAC1, Mrg15, and the PHD finger-containing Pf1 and show that this complex plays important roles in regulation of transcription. We demonstrate that this complex localizes at discrete loci approximately 1 kb downstream of the transcription start site of transcribed genes, and this localization requires both Pf1's and Mrg15's interaction with chromatin. Inactivation of this mammalian complex promotes increased RNAP II progression within transcribed regions and subsequent increased transcription. Our results define a novel mammalian complex that contributes to the regulation of transcription and point to divergent uses of the Sin3 protein homologues throughout evolution in the modulation of transcription. PMID:21041482

Costing Complex Products, Operations & Support

DTIC Science & Technology

2011-10-19

last version of the Harrier II family introduced in the UK. As such it is similar to the U.S. Marine Corps’ AV-8B in basic structure , systems , and...ABSTRACT Complex products and systems (CoPS) are major capital goods in which customers play a central role from design through to disposal, such as...Complex products and systems (CoPS) are major capital goods in which customers play a central role from design through to disposal, such as large defense

Polarimetric SAR image classification based on discriminative dictionary learning model

NASA Astrophysics Data System (ADS)

Sang, Cheng Wei; Sun, Hong

2018-03-01

Polarimetric SAR (PolSAR) image classification is one of the important applications of PolSAR remote sensing. It is a difficult high-dimension nonlinear mapping problem, the sparse representations based on learning overcomplete dictionary have shown great potential to solve such problem. The overcomplete dictionary plays an important role in PolSAR image classification, however for PolSAR image complex scenes, features shared by different classes will weaken the discrimination of learned dictionary, so as to degrade classification performance. In this paper, we propose a novel overcomplete dictionary learning model to enhance the discrimination of dictionary. The learned overcomplete dictionary by the proposed model is more discriminative and very suitable for PolSAR classification.

The Elements of Play: Toward a Philosophy and a Definition of Play

ERIC Educational Resources Information Center

Eberle, Scott G.

2014-01-01

Scholars conventionally find play difficult to define because the concept is complex and ambiguous. The author proffers a definition of play that takes into consideration its dynamic character, posits six basic elements of play (anticipation, surprise, pleasure, understanding, strength, and poise), and explores some of their emotional, physical,…

Crystal and solution structures of an odorant-binding protein from the southern house mosquito complexed with an oviposition pheromone

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

Mao, Yang; Xu, Xianzhong; Xu, Wei

2010-11-15

Culex mosquitoes introduce the pathogens responsible for filariasis, West Nile virus, St. Louis encephalitis, and other diseases into humans. Currently, traps baited with oviposition semiochemicals play an important role in detection efforts and could provide an environmentally friendly approach to controlling their populations. The odorant binding proteins (OBPs) in the female's antenna play a crucial, if yet imperfectly understood, role in sensing oviposition cues. Here, we report the X-ray crystallography and NMR 3D structures of OBP1 for Culex quinquefasciatus (CquiOBP1) bound to an oviposition pheromone (5R,6S)-6-acetoxy-5-hexadecanolide (MOP). In both studies, CquiOBP1 had the same overall six-helix structure seen in othermore » insect OBPs, but a detailed analysis revealed an important previously undescribed feature. There are two models for OBP-mediated signal transduction: (i) direct release of the pheromone from an internal binding pocket in a pH-dependent fashion and (ii) detection of a pheromone-induced conformational change in the OBP {center_dot} pheromone complex. Although CquiOBP1 binds MOP in a pH-dependent fashion, it lacks the C terminus required for the pH-dependent release model. This study shows that CquiOBP binds MOP in an unprecedented fashion using both a small central cavity for the lactone head group and a long hydrophobic channel for its tail.« less

Role of miRNAs in CD4 T cell plasticity during inflammation and tolerance

PubMed Central

Sethi, Apoorva; Kulkarni, Neeraja; Sonar, Sandip; Lal, Girdhari

2013-01-01

Gene expression is tightly regulated in a tuneable, cell-specific and time-dependent manner. Recent advancement in epigenetics and non-coding RNA (ncRNA) revolutionized the concept of gene regulation. In order to regulate the transcription, ncRNA can promptly response to the extracellular signals as compared to transcription factors present in the cells. microRNAs (miRNAs) are ncRNA (~22 bp) encoded in the genome, and present as intergenic or oriented antisense to neighboring genes. The strategic location of miRNA in coding genes helps in the coupled regulation of its expression with host genes. miRNA together with complex machinery called RNA-induced silencing complex (RISC) interacts with target mRNA and degrade the mRNA or inhibits the translation. CD4 T cells play an important role in the generation and maintenance of inflammation and tolerance. Cytokines and chemokines present in the inflamed microenvironment controls the differentiation and function of various subsets of CD4 T cells [Th1, Th2, Th17, and regulatory CD4 T cells (Tregs)]. Recent studies suggest that miRNAs play an important role in the development and function of all subsets of CD4 T cells. In current review, we focused on how various miRNAs are regulated by cell's extrinsic and intrinsic signaling, and how miRNAs affect the transdifferentiation of subsets of CD4 T cell and controls their plasticity during inflammation and tolerance. PMID:23386861

S100A8 Contributes to Drug Resistance by Promoting Autophagy in Leukemia Cells

PubMed Central

Yang, Minghua; Zeng, Pei; Kang, Rui; Yu, Yan; Yang, Liangchun; Tang, Daolin; Cao, Lizhi

2014-01-01

Autophagy is a double-edged sword in tumorigenesis and plays an important role in the resistance of cancer cells to chemotherapy. S100A8 is a member of the S100 calcium-binding protein family and plays an important role in the drug resistance of leukemia cells, with the mechanisms largely unknown. Here we report that S100A8 contributes to drug resistance in leukemia by promoting autophagy. S100A8 level was elevated in drug resistance leukemia cell lines relative to the nondrug resistant cell lines. Adriamycin and vincristine increased S100A8 in human leukemia cells, accompanied with upregulation of autophagy. RNA interference-mediated knockdown of S100A8 restored the chemosensitivity of leukemia cells, while overexpression of S100A8 enhanced drug resistance and increased autophagy. S100A8 physically interacted with the autophagy regulator BECN1 and was required for the formation of the BECN1-PI3KC3 complex. In addition, interaction between S100A8 and BECN1 relied upon the autophagic complex ULK1-mAtg13. Furthermore, we discovered that exogenous S100A8 induced autophagy, and RAGE was involved in exogenous S100A8-regulated autophagy. Our data demonstrated that S100A8 is involved in the development of chemoresistance in leukemia cells by regulating autophagy, and suggest that S100A8 may be a novel target for improving leukemia therapy. PMID:24820971

Larval Settlement: The Role of Surface Topography for Sessile Coral Reef Invertebrates

PubMed Central

Whalan, Steve; Abdul Wahab, Muhammad A.; Sprungala, Susanne; Poole, Andrew J.; de Nys, Rocky

2015-01-01

For sessile marine invertebrates with complex life cycles, habitat choice is directed by the larval phase. Defining which habitat-linked cues are implicated in sessile invertebrate larval settlement has largely concentrated on chemical cues which are thought to signal optimal habitat. There has been less effort establishing physical settlement cues, including the role of surface microtopography. This laboratory based study tested whether surface microtopography alone (without chemical cues) plays an important contributing role in the settlement of larvae of coral reef sessile invertebrates. We measured settlement to tiles, engineered with surface microtopography (holes) that closely matched the sizes (width) of larvae of a range of corals and sponges, in addition to surfaces with holes that were markedly larger than larvae. Larvae from two species of scleractinian corals (Acropora millepora and Ctenactis crassa) and three species of coral reef sponges (Luffariella variabilis, Carteriospongia foliascens and Ircinia sp.,) were used in experiments. L. variabilis, A. millepora and C. crassa showed markedly higher settlement to surface microtopography that closely matched their larval width. C. foliascens and Ircinia sp., showed no specificity to surface microtopography, settling just as often to microtopography as to flat surfaces. The findings of this study question the sole reliance on chemical based larval settlement cues, previously established for some coral and sponge species, and demonstrate that specific physical cues (surface complexity) can also play an important role in larval settlement of coral reef sessile invertebrates. PMID:25671562

Regulation of the Hippo signaling pathway by ubiquitin modification.

PubMed

Kim, Youngeun; Jho, Eek-Hoon

2018-03-01

The Hippo signaling pathway plays an essential role in adult tissue homeostasis and organ size control. Abnormal regulation of Hippo signaling can be a cause for multiple types of human cancers. Since the awareness of the importance of the Hippo signaling in a wide range of biological fields has been continually grown, it is also understood that a thorough and well-rounded comprehension of the precise dynamics could provide fundamental insights for therapeutic applications. Several components in the Hippo signaling pathway are known to be targeted for proteasomal degradation via ubiquitination by E3 ligases. β-TrCP is a well-known E3 ligase of YAP/TAZ, which leads to the reduction of YAP/TAZ levels. The Hippo signaling pathway can also be inhibited by the E3 ligases (such as ITCH) which target LATS1/2 for degradation. Regulation via ubiquitination involves not only complex network of E3 ligases but also deubiquitinating enzymes (DUBs), which remove ubiquitin from its targets. Interestingly, non-degradative ubiquitin modifications are also known to play important roles in the regulation of Hippo signaling. Although there has been much advanced progress in the investigation of ubiquitin modifications acting as regulators of the Hippo signaling pathway, research done to date still remains inadequate due to the sheer complexity and diversity of the subject. Herein, we review and discuss recent developments that implicate ubiquitin-mediated regulatory mechanisms at multiple steps of the Hippo signaling pathway. [BMB Reports 2018; 51(3): 143-150].

Larval settlement: the role of surface topography for sessile coral reef invertebrates.

PubMed

Whalan, Steve; Wahab, Muhammad A Abdul; Sprungala, Susanne; Poole, Andrew J; de Nys, Rocky

2015-01-01

For sessile marine invertebrates with complex life cycles, habitat choice is directed by the larval phase. Defining which habitat-linked cues are implicated in sessile invertebrate larval settlement has largely concentrated on chemical cues which are thought to signal optimal habitat. There has been less effort establishing physical settlement cues, including the role of surface microtopography. This laboratory based study tested whether surface microtopography alone (without chemical cues) plays an important contributing role in the settlement of larvae of coral reef sessile invertebrates. We measured settlement to tiles, engineered with surface microtopography (holes) that closely matched the sizes (width) of larvae of a range of corals and sponges, in addition to surfaces with holes that were markedly larger than larvae. Larvae from two species of scleractinian corals (Acropora millepora and Ctenactis crassa) and three species of coral reef sponges (Luffariella variabilis, Carteriospongia foliascens and Ircinia sp.,) were used in experiments. L. variabilis, A. millepora and C. crassa showed markedly higher settlement to surface microtopography that closely matched their larval width. C. foliascens and Ircinia sp., showed no specificity to surface microtopography, settling just as often to microtopography as to flat surfaces. The findings of this study question the sole reliance on chemical based larval settlement cues, previously established for some coral and sponge species, and demonstrate that specific physical cues (surface complexity) can also play an important role in larval settlement of coral reef sessile invertebrates.

Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934.

PubMed

Ulrich, Veronika; Brieke, Clara; Cryle, Max J

2016-01-01

The chemical complexity and biological activity of the glycopeptide antibiotics (GPAs) stems from their unique crosslinked structure, which is generated by the actions of cytochrome P450 (Oxy) enzymes that affect the crosslinking of aromatic side chains of amino acid residues contained within the GPA heptapeptide precursor. Given the crucial role peptide cyclisation plays in GPA activity, the characterisation of this process is of great importance in understanding the biosynthesis of these important antibiotics. Here, we report the cyclisation activity and crystal structure of StaF, the D- O -E ring forming Oxy enzyme from A47934 biosynthesis. Our results show that the specificity of StaF is reduced when compared to Oxy enzymes catalysing C- O -D ring formation and that this activity relies on interactions with the non-ribosomal peptide synthetase via the X-domain. Despite the interaction of StaF with the A47934 X-domain being weaker than for the preceding Oxy enzyme StaH, StaF retains higher levels of in vitro activity: we postulate that this is due to the ability of the StaF/X-domain complex to allow substrate reorganisation after initial complex formation has occurred. These results highlight the importance of testing different peptide/protein carrier constructs for in vitro GPA cyclisation assays and show that different Oxy homologues can display significantly different catalytic propensities despite their overall similarities.

The role of the VZn-NO-H complex in the p-type conductivity in ZnO.

PubMed

Amini, M N; Saniz, R; Lamoen, D; Partoens, B

2015-02-21

Past research efforts aiming at obtaining stable p-type ZnO have been based on complexes involving nitrogen doping. A recent experiment by (J. G. Reynolds et al., Appl. Phys. Lett., 2013, 102, 152114) demonstrated a significant (∼10(18) cm(-3)) p-type behavior in N-doped ZnO films after appropriate annealing. The p-type conductivity was attributed to a VZn-NO-H shallow acceptor complex, formed by a Zn vacancy (VZn), N substituting O (NO), and H interstitial (Hi). We present here a first-principles hybrid functional study of this complex compared to the one without hydrogen. Our results confirm that the VZn-NO-H complex acts as an acceptor in ZnO. We find that H plays an important role, because it lowers the formation energy of the complex with respect to VZn-NO, a complex known to exhibit (unstable) p-type behavior. However, this additional H atom also occupies the hole level at the origin of the shallow behavior of VZn-NO, leaving only two states empty higher in the band gap and making the VZn-NO-H complex a deep acceptor. Therefore, we conclude that the cause of the observed p-type conductivity in experiment is not the presence of the VZn-NO-H complex, but probably the formation of the VZn-NO complex during the annealing process.

The Use of Play Expansions to Increase the Diversity and Complexity of Object Play in Young Children with Disabilities

ERIC Educational Resources Information Center

Frey, Jennifer R.; Kaiser, Ann P.

2011-01-01

The purpose of this study was to determine if an intervention consisting of contingently imitating play, modeling expansions of play actions, and describing play actions increased the diversity of object play in young children with disabilities. The multicomponent intervention was introduced in a multiple-probe design across three young children…

GenPlay Multi-Genome, a tool to compare and analyze multiple human genomes in a graphical interface.

PubMed

Lajugie, Julien; Fourel, Nicolas; Bouhassira, Eric E

2015-01-01

Parallel visualization of multiple individual human genomes is a complex endeavor that is rapidly gaining importance with the increasing number of personal, phased and cancer genomes that are being generated. It requires the display of variants such as SNPs, indels and structural variants that are unique to specific genomes and the introduction of multiple overlapping gaps in the reference sequence. Here, we describe GenPlay Multi-Genome, an application specifically written to visualize and analyze multiple human genomes in parallel. GenPlay Multi-Genome is ideally suited for the comparison of allele-specific expression and functional genomic data obtained from multiple phased genomes in a graphical interface with access to multiple-track operation. It also allows the analysis of data that have been aligned to custom genomes rather than to a standard reference and can be used as a variant calling format file browser and as a tool to compare different genome assembly, such as hg19 and hg38. GenPlay is available under the GNU public license (GPL-3) from http://genplay.einstein.yu.edu. The source code is available at https://github.com/JulienLajugie/GenPlay. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

How important are rare variants in common disease?

PubMed

Saint Pierre, Aude; Génin, Emmanuelle

2014-09-01

Genome-wide association studies have uncovered hundreds of common genetic variants involved in complex diseases. However, for most complex diseases, these common genetic variants only marginally contribute to disease susceptibility. It is now argued that rare variants located in different genes could in fact play a more important role in disease susceptibility than common variants. These rare genetic variants were not captured by genome-wide association studies using single nucleotide polymorphism-chips but with the advent of next-generation sequencing technologies, they have become detectable. It is now possible to study their contribution to common disease by resequencing samples of cases and controls or by using new genotyping exome arrays that cover rare alleles. In this review, we address the question of the contribution of rare variants in common disease by taking the examples of different diseases for which some resequencing studies have already been performed, and by summarizing the results of simulation studies conducted so far to investigate the genetic architecture of complex traits in human. So far, empirical data have not allowed the exclusion of many models except the most extreme ones involving only a small number of rare variants with large effects contributing to complex disease. To unravel the genetic architecture of complex disease, case-control data will not be sufficient, and alternative study designs need to be proposed together with methodological developments. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Rapidly progressive Scheuermann's disease in an adolescent after pectus bar placement treated with posterior vertebral-column resection: case report and review of the literature.

PubMed

Sugrue, Patrick A; OʼShaughnessy, Brian A; Blanke, Kathy M; Lenke, Lawrence G

2013-02-15

Case report and review of the literature. This case illustrates the importance of the costosternal complex in maintaining the stability and alignment of the thoracic spine. The patient was iatrogenically destabilized by placement of a pectus bar leading to rapid symptomatic progression of his Scheuermann's kyphosis, ultimately requiring surgical correction. Scheuermann's kyphosis is a disease process defined by strict radiographical and clinical criteria. Surgical treatment is generally recommended for curves greater than 75°. This case demonstrates the critical role of the costosternal complex in maintaining the stability of the thoracic spine. The patient described in this report underwent placement of a pectus bar for correction of symptomatic pectus excavatum. He subsequently developed a progressive symptomatic Scheuermann's kyphosis as a result of the destabilization of his costosternal complex. This patient ultimately required removal of the pectus bar and posterior instrumented kyphosis correction. Progressive symptomatic Scheuermann's kyphosis (105°) corrected by removal of the pectus bar, T11 posterior vertebral-column resection and T4-L3 instrumented posterior spinal fusion. The patient had an uneventful immediate postoperative course. He was discharged neurologically intact with dramatic kyphosis correction and significant symptomatic improvement. Radiographs obtained 3 years postoperatively reveal stable thoracolumbar correction. The costosternal complex plays a critically important role in the intrinsic stability of the thoracic spine. Iatrogenic disruption of the costosternal complex can result in rapid progression of thoracic/thoracolumbar kyphosis in the setting of Scheuermann's disease.

Transitions from mono- to co- to tri-culture uniquely affect gene expression in breast cancer, stromal, and immune compartments.

PubMed

Regier, Mary C; Maccoux, Lindsey J; Weinberger, Emma M; Regehr, Keil J; Berry, Scott M; Beebe, David J; Alarid, Elaine T

2016-08-01

Heterotypic interactions in cancer microenvironments play important roles in disease initiation, progression, and spread. Co-culture is the predominant approach used in dissecting paracrine interactions between tumor and stromal cells, but functional results from simple co-cultures frequently fail to correlate to in vivo conditions. Though complex heterotypic in vitro models have improved functional relevance, there is little systematic knowledge of how multi-culture parameters influence this recapitulation. We therefore have employed a more iterative approach to investigate the influence of increasing model complexity; increased heterotypic complexity specifically. Here we describe how the compartmentalized and microscale elements of our multi-culture device allowed us to obtain gene expression data from one cell type at a time in a heterotypic culture where cells communicated through paracrine interactions. With our device we generated a large dataset comprised of cell type specific gene-expression patterns for cultures of increasing complexity (three cell types in mono-, co-, or tri-culture) not readily accessible in other systems. Principal component analysis indicated that gene expression was changed in co-culture but was often more strongly altered in tri-culture as compared to mono-culture. Our analysis revealed that cell type identity and the complexity around it (mono-, co-, or tri-culture) influence gene regulation. We also observed evidence of complementary regulation between cell types in the same heterotypic culture. Here we demonstrate the utility of our platform in providing insight into how tumor and stromal cells respond to microenvironments of varying complexities highlighting the expanding importance of heterotypic cultures that go beyond conventional co-culture.

Beyond disease susceptibility-Leveraging genome-wide association studies for new insights into complex disease biology.

PubMed

Lee, J C

2017-12-01

Genetic studies in complex diseases have been highly successful, but have also been largely one-dimensional: predominantly focusing on the genetic contribution to disease susceptibility. While this is undoubtedly important-indeed it is a pre-requisite for understanding the mechanisms underlying disease development-there are many other important aspects of disease biology that have received comparatively little attention. In this review, I will discuss how existing genetic data can be leveraged to provide new insights into other aspects of disease biology, why such insights could change the way we think about complex disease, and how this could provide opportunities for better therapies and/or facilitate personalised medicine. To do this, I will use the example of Crohn's disease-a chronic form of inflammatory bowel disease that has been one of the main success stories in complex disease genetics. Indeed, thanks to genetic studies, we now have a much more detailed understanding of the processes involved in Crohn's disease development, but still know relatively little about what determines the subsequent disease course (prognosis) and why this differs so considerably between individuals. I will discuss how we came to realise that genetic variation plays an important role in determining disease prognosis and how this has changed the way we think about Crohn's disease genetics. This will illustrate how phenotypic data can be used to leverage new insights from genetic data and will provide a broadly applicable framework that could yield new insights into the biology of multiple diseases. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes

PubMed Central

Schreiner, Sabrina; Bürck, Carolin; Glass, Mandy; Groitl, Peter; Wimmer, Peter; Kinkley, Sarah; Mund, Andreas; Everett, Roger D.; Dobner, Thomas

2013-01-01

Death domain–associated protein (Daxx) cooperates with X-linked α-thalassaemia retardation syndrome protein (ATRX), a putative member of the sucrose non-fermentable 2 family of ATP-dependent chromatin-remodelling proteins, acting as the core ATPase subunit in this complex, whereas Daxx is the targeting factor, leading to histone deacetylase recruitment, H3.3 deposition and transcriptional repression of cellular promoters. Despite recent findings on the fundamental importance of chromatin modification in host-cell gene regulation, it remains unclear whether adenovirus type 5 (Ad5) transcription is regulated by cellular chromatin remodelling to allow efficient virus gene expression. Here, we focus on the repressive role of the Daxx/ATRX complex during Ad5 replication, which depends on intact protein–protein interaction, as negative regulation could be relieved with a Daxx mutant that is unable to interact with ATRX. To ensure efficient viral replication, Ad5 E1B-55K protein inhibits Daxx and targets ATRX for proteasomal degradation in cooperation with early region 4 open reading frame protein 6 and cellular components of a cullin-dependent E3-ubiquitin ligase. Our studies illustrate the importance and diversity of viral factors antagonizing Daxx/ATRX-mediated repression of viral gene expression and shed new light on the modulation of cellular chromatin remodelling factors by Ad5. We show for the first time that cellular Daxx/ATRX chromatin remodelling complexes play essential roles in Ad gene expression and illustrate the importance of early viral proteins to counteract cellular chromatin remodelling. PMID:23396441

Identification of core components and transient interactors of the peroxisomal importomer by dual-track stable isotope labeling with amino acids in cell culture analysis.

PubMed

Oeljeklaus, Silke; Reinartz, Benedikt S; Wolf, Janina; Wiese, Sebastian; Tonillo, Jason; Podwojski, Katharina; Kuhlmann, Katja; Stephan, Christian; Meyer, Helmut E; Schliebs, Wolfgang; Brocard, Cécile; Erdmann, Ralf; Warscheid, Bettina

2012-04-06

The importomer complex plays an essential role in the biogenesis of peroxisomes by mediating the translocation of matrix proteins across the organellar membrane. A central part of this highly dynamic import machinery is the docking complex consisting of Pex14p, Pex13p, and Pex17p that is linked to the RING finger complex (Pex2p, Pex10p, Pex12p) via Pex8p. To gain detailed knowledge on the molecular players governing peroxisomal matrix protein import and, thus, the integrity and functionality of peroxisomes, we aimed at a most comprehensive investigation of stable and transient interaction partners of Pex14p, the central component of the importomer. To this end, we performed a thorough quantitative proteomics study based on epitope tagging of Pex14p combined with dual-track stable isotope labeling with amino acids in cell culture-mass spectrometry (SILAC-MS) analysis of affinity-purified Pex14p complexes and statistics. The results led to the establishment of the so far most extensive Pex14p interactome, comprising 9 core and further 12 transient components. We confirmed virtually all known Pex14p interaction partners including the core constituents of the importomer as well as Pex5p, Pex11p, Pex15p, and Dyn2p. More importantly, we identified new transient interaction partners (Pex25p, Hrr25p, Esl2p, prohibitin) that provide a valuable resource for future investigations on the functionality, dynamics, and regulation of the peroxisomal importomer.

Already at the Table: Patterns of Play and Gambling Involvement Prior to Gambling Expansion.

PubMed

Nelson, Sarah E; LaPlante, Debi A; Gray, Heather M; Tom, Matthew A; Kleschinsky, John H; Shaffer, Howard J

2018-03-01

During 2011, the Governor of Massachusetts signed a bill to allow casino gambling in the state (Commonwealth of Massachusetts 2011). As a result, two resort casinos will begin operations during 2018 and 2019; a smaller slots parlor began operations during June 2015. Prior to this expansion, gambling was widely available in Massachusetts, through the state lottery, off-track betting, and gambling opportunities available in neighboring states. Within this context, it is important to understand the patterns of gambling involvement in the population prior to gambling expansion. The current study examined gambling involvement, patterns of play, and gambling-related problems prior to gambling expansion among a sample of 511 Massachusetts residents who were members of a statewide Internet panel. To measure patterns of play, we asked questions about past-year games played and frequency of play. To measure breadth of involvement, we assessed the number of different games played. To measure depth of involvement, we measured time spent gambling, amount wagered, and amount won or lost. Principal component analysis revealed four play pattern components accounting for more than 50% of the variance in game play frequency. Multiple regression analyses revealed that component scores composed of casino gambling and skill-based gambling (e.g., poker, sports) variables uniquely contributed to the prediction of gambling-related problems, even when depth of involvement was controlled. However, the addition of breadth of involvement to the model resulted in a model where no set of variables contributed significantly, suggesting a complex relationship among play patterns, depth, and breadth of involvement. The study established discrete and distinguishable gambling play patterns associated with gambling-related problems and identified groups of individuals potentially vulnerable to the effects of gambling expansion.

MiR-21 is enriched in the RNA-induced silencing complex and targets COL4A1 in human granulosa cell lines.

PubMed

Mase, Yuri; Ishibashi, Osamu; Ishikawa, Tomoko; Takizawa, Takami; Kiguchi, Kazushige; Ohba, Takashi; Katabuchi, Hidetaka; Takeshita, Toshiyuki; Takizawa, Toshihiro

2012-10-01

MicroRNAs (miRNAs) are noncoding small RNAs that play important roles in a variety of physiological and pathological events. In this study, we performed large-scale profiling of EIF2C2-bound miRNAs in 3 human granulosa-derived cell lines (ie, KGN, HSOGT, and GC1a) by high-throughput sequencing and found that miR-21 accounted for more than 80% of EIF2C2-bound miRNAs, suggesting that it was enriched in the RNA-induced silencing complex (RISC) and played a functional role in human granulosa cell (GC) lines. We also found high expression levels of miR-21 in primary human GCs. Assuming that miR-21 target mRNAs are enriched in RISC, we performed cDNA cloning of EIF2C2-bound mRNAs in KGN cells. We identified COL4A1 mRNA as a miR-21 target in the GC lines. These data suggest that miR-21 is involved in the regulation of the synthesis of COL4A1, a component of the basement membrane surrounding the GC layer and granulosa-embedded extracellular structure.

Obesity and Metabolic Comorbidities: Environmental Diseases?

PubMed Central

Lubrano, Carla; Genovesi, Giuseppe; Specchia, Palma; Costantini, Daniela; Mariani, Stefania; Petrangeli, Elisa; Lenzi, Andrea; Gnessi, Lucio

2013-01-01

Obesity and metabolic comorbidities represent increasing health problems. Endocrine disrupting compounds (EDCs) are exogenous agents that change endocrine function and cause adverse health effects. Most EDCs are synthetic chemicals; some are natural food components as phytoestrogens. People are exposed to complex mixtures of chemicals throughout their lives. EDCs impact hormone-dependent metabolic systems and brain function. Laboratory and human studies provide compelling evidence that human chemical contamination can play a role in obesity epidemic. Chemical exposures may increase the risk of obesity by altering the differentiation of adipocytes. EDCs can alter methylation patterns and normal epigenetic programming in cells. Oxidative stress may be induced by many of these chemicals, and accumulating evidence indicates that it plays important roles in the etiology of chronic diseases. The individual sensitivity to chemicals is variable, depending on environment and ability to metabolize hazardous chemicals. A number of genes, especially those representing antioxidant and detoxification pathways, have potential application as biomarkers of risk assessment. The potential health effects of combined exposures make the risk assessment process more complex compared to the assessment of single chemicals. Techniques and methods need to be further developed to fill data gaps and increase the knowledge on harmful exposure combinations. PMID:23577225

Genetics of liver disease: From pathophysiology to clinical practice.

PubMed

Karlsen, Tom H; Lammert, Frank; Thompson, Richard J

2015-04-01

Paralleling the first 30 years of the Journal of Hepatology we have witnessed huge advances in our understanding of liver disease and physiology. Genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990 s, developments in genomic technologies drove the identification of genes responsible for Mendelian liver diseases. Over the last decade, genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders, in which also environmental co-factors play important roles. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data. The historical perspective of genetics in liver diseases illustrates the opportunities for future research and clinical care of our patients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Fantasy Play of Preschoolers as a Function of Toy Structures.

ERIC Educational Resources Information Center

Einsiedler, Wolfgang

Two studies are presented which investigate the influence of various toy structures on the frequency of individual fantasy play forms in 3- to 6-year-old children. In the first study, the effects of high-realistic/high-complexity and low-realistic/low-complexity toy structures were compared. There were significant main effects for the factor toy…

Microsurgical and Tractographic Anatomy of the Supplementary Motor Area Complex in Humans.

PubMed

Bozkurt, Baran; Yagmurlu, Kaan; Middlebrooks, Erik H; Karadag, Ali; Ovalioglu, Talat Cem; Jagadeesan, Bharathi; Sandhu, Gauravjot; Tanriover, Necmettin; Grande, Andrew W

2016-11-01

To evaluate the microsurgical anatomy of the fiber tract connections of the supplementary motor area (SMA) and pre-SMA, and examine its potential functional role with reference to clinical trials in the literature. Ten postmortem formalin-fixed human brains (20 sides) and 1 cadaveric head were prepared following Klingler's method. The fiber dissection was performed in a stepwise fashion, from lateral to medial and also from medial to lateral, under an operating microscope, with 3D images captured at each stage. Our findings were supported by in vivo magnetic resonance imaging tractography in 2 healthy subjects. The connections of the SMA complex, composed of the pre-SMA and the SMA proper, are composed of short "U" association fibers and the superior longitudinal fasciculus I, cingulum, claustrocortical fibers, callosal fibers, corticospinal tract, frontal aslant tract, and frontostriatal tract. The claustrocortical fibers may play an important role in the integration of motor, language, and limbic functions of the SMA complex. The frontostriatal tract connects the pre-SMA to the putamen and caudate nucleus, and also forms parts of both the internal capsule and the dorsal external capsule. The SMA complex has numerous connections throughout the cerebrum. An understanding of these connections is important for presurgical planning for lesions in the frontal lobe and helps explain symptoms related to SMA injury. Copyright © 2016 Elsevier Inc. All rights reserved.

The Role of γδ T Cells in Fibrotic Diseases.

PubMed

Bank, Ilan

2016-10-31

Inflammation induced by toxins, micro-organisms, or autoimmunity may result in pathogenic fibrosis, leading to long-term tissue dysfunction, morbidity, and mortality. Immune cells play a role in both induction and resolution of fibrosis. γδ T cells are an important group of unconventional T cells characterized by their expression of non-major histocompatibility complex restricted clonotypic T cell receptors for non-peptide antigens. Accumulating evidence suggests that subsets of γδ T cells in experimentally induced fibrosis following bleomycin treatment, or infection with Bacillus subtilis, play pro-inflammatory roles that instigate fibrosis, whereas the same cells may also play a role in resolving fibrosis. These processes appear to be linked at least in part to the cytokines produced by the cells at various stages, with interleukin (IL)-17 playing a central role in the inflammatory phase driving fibrosis, but later secretion of IL-22, interferon γ, and CXCL10 preventing pathologic fibrosis. Moreover, γδ T cells appear to be involved, in an antigen-driven manner, in the prototypic human fibrotic disease, systemic sclerosis (SSc). In this paper we review in brief the scientific publications that have implicated γδ T cells in fibrotic diseases and their pro- and anti-fibrotic effects.

The Role of γδ T Cells in Fibrotic Diseases

PubMed Central

Bank, Ilan

2016-01-01

Inflammation induced by toxins, micro-organisms, or autoimmunity may result in pathogenic fibrosis, leading to long-term tissue dysfunction, morbidity, and mortality. Immune cells play a role in both induction and resolution of fibrosis. γδ T cells are an important group of unconventional T cells characterized by their expression of non-major histocompatibility complex restricted clonotypic T cell receptors for non-peptide antigens. Accumulating evidence suggests that subsets of γδ T cells in experimentally induced fibrosis following bleomycin treatment, or infection with Bacillus subtilis, play pro-inflammatory roles that instigate fibrosis, whereas the same cells may also play a role in resolving fibrosis. These processes appear to be linked at least in part to the cytokines produced by the cells at various stages, with interleukin (IL)-17 playing a central role in the inflammatory phase driving fibrosis, but later secretion of IL-22, interferon γ, and CXCL10 preventing pathologic fibrosis. Moreover, γδ T cells appear to be involved, in an antigen-driven manner, in the prototypic human fibrotic disease, systemic sclerosis (SSc). In this paper we review in brief the scientific publications that have implicated γδ T cells in fibrotic diseases and their pro- and anti-fibrotic effects. PMID:27824548