The Embedded Self: A Social Networks Approach to Identity Theory

ERIC Educational Resources Information Center

Walker, Mark H.; Lynn, Freda B.

2013-01-01

Despite the fact that key sociological theories of self and identity view the self as fundamentally rooted in networks of interpersonal relationships, empirical research investigating how personal network structure influences the self is conspicuously lacking. To address this gap, we examine links between network structure and role identity…

21st Century Manufacturing Supervisors and Their Historical Roots

ERIC Educational Resources Information Center

Hotek, Douglas R.

2003-01-01

This article provides a perspective of the past and present roles of the manufacturing supervisor with a specific focus on new skills requirements. Within the structure of manufacturing management, the supervisor plays a key role in implementing today's complex automated manufacturing technologies. The supervisor is at the bottom of the management…

The nanoscale organization of signaling domains at the plasma membrane.

PubMed

Griffié, Juliette; Burn, Garth; Owen, Dylan M

2015-01-01

In this chapter, we present an overview of the role of the nanoscale organization of signaling domains in regulating key cellular processes. In particular, we illustrate the importance of protein and lipid nanodomains as triggers and mediators of cell signaling. As particular examples, we summarize the state of the art of understanding the role of nanodomains in the mounting of an immune response, cellular adhesion, intercellular communication, and cell proliferation. Thus, this chapter underlines the essential role the nanoscale organization of key signaling proteins and lipid domains. We will also see how nanodomains play an important role in the lifecycle of many pathogens relevant to human disease and therefore illustrate how these structures may become future therapeutic targets. Copyright © 2015 Elsevier Inc. All rights reserved.

School Governance Structures that Foster Friendship in the Elementary School.

ERIC Educational Resources Information Center

Kuhmerker, Lisa

1989-01-01

Uses examples from the Schaefer School in Tappan (New York) to illustrate how an elementary school can develop an educational climate that fosters friendship, the key to student socialization. Discusses the following areas: (1) classroom activities; (2) school-wide democratic governance structures; (3) support staff roles; and (4) time scheduling.…

The Use of Polymerized Genipin for the Stabilization of the Collagen Structure of Animal Hides

USDA-ARS?s Scientific Manuscript database

Animal hides are the major byproduct of meat industry and the collagen fibers is the main constituent. Crosslinkers play a key role in stabilizing the collagen structure for useful applications. Genipin is widely used as an ideal biological protein crosslinking agent due to its low toxicity compare...

Quality Guidance: A Sectoral Analysis. NICEC Project Report.

ERIC Educational Resources Information Center

Watts, A. G.; Sadler, Jackie

This report reviews the structure of the guidance field and provides a sector-by-sector analysis of current quality assurance arrangements in the United Kingdom. Part 1 presents an outline of the guidance sector, including some key concepts, structures, and roles. It defines guidance and other terms; discusses the three main categories…

The Relationship of Morphological Analysis and Morphological Decoding to Reading Comprehension

ERIC Educational Resources Information Center

Deacon, S. Hélène; Tong, Xiuli; Francis, Kathryn

2017-01-01

The ultimate goal of children's reading development is the full and fluid understanding of texts. Morphological structure awareness, or children's awareness of the minimal units of meaning in language, has been identified as a key skill influencing reading comprehension. Here, we evaluate the roles of morphological structure awareness and two…

The structure of human DNase I bound to magnesium and phosphate ions points to a catalytic mechanism common to members of the DNase I-like superfamily.

PubMed

Parsiegla, Goetz; Noguere, Christophe; Santell, Lydia; Lazarus, Robert A; Bourne, Yves

2012-12-21

Recombinant human DNase I (Pulmozyme, dornase alfa) is used for the treatment of cystic fibrosis where it improves lung function and reduces the number of exacerbations. The physiological mechanism of action is thought to involve the reduction of the viscoelasticity of cystic fibrosis sputum by hydrolyzing high concentrations of DNA into low-molecular mass fragments. Here we describe the 1.95 Å resolution crystal structure of recombinant human DNase I (rhDNase I) in complex with magnesium and phosphate ions, both bound in the active site. Complementary mutagenesis data of rhDNase I coupled to a comprehensive structural analysis of the DNase I-like superfamily argue for the key catalytic role of Asn7, which is invariant among mammalian DNase I enzymes and members of this superfamily, through stabilization of the magnesium ion coordination sphere. Overall, our combined structural and mutagenesis data suggest the occurrence of a magnesium-assisted pentavalent phosphate transition state in human DNase I during catalysis, where Asp168 may play a key role as a general catalytic base.

Computer-Assisted Instruction and Increased Educational Productivity

ERIC Educational Resources Information Center

Cropley, A. J.; Gross, P. F.

1973-01-01

Describes the role of computer-assisted instruction (CAI) in increasing educational productivity and equality of opportunity. Examines a number of key questions concerning the interrelationship of CAI with the traditional education structure. (Authors/WM)

FANCJ suppresses microsatellite instability and lymphomagenesis independent of the Fanconi anemia pathway.

PubMed

Matsuzaki, Kenichiro; Borel, Valerie; Adelman, Carrie A; Schindler, Detlev; Boulton, Simon J

2015-12-15

Microsatellites are short tandem repeat sequences that are highly prone to expansion/contraction due to their propensity to form non-B-form DNA structures, which hinder DNA polymerases and provoke template slippage. Although error correction by mismatch repair plays a key role in preventing microsatellite instability (MSI), which is a hallmark of Lynch syndrome, activities must also exist that unwind secondary structures to facilitate replication fidelity. Here, we report that Fancj helicase-deficient mice, while phenotypically resembling Fanconi anemia (FA), are also hypersensitive to replication inhibitors and predisposed to lymphoma. Whereas metabolism of G4-DNA structures is largely unaffected in Fancj(-/-) mice, high levels of spontaneous MSI occur, which is exacerbated by replication inhibition. In contrast, MSI is not observed in Fancd2(-/-) mice but is prevalent in human FA-J patients. Together, these data implicate FANCJ as a key factor required to counteract MSI, which is functionally distinct from its role in the FA pathway. © 2015 Matsuzaki et al.; Published by Cold Spring Harbor Laboratory Press.

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.

Ditch network sustains functional connectivity and influences patterns of gene flow in an intensive agricultural landscape

PubMed Central

Favre-Bac, L; Mony, C; Ernoult, A; Burel, F; Arnaud, J-F

2016-01-01

In intensive agricultural landscapes, plant species previously relying on semi-natural habitats may persist as metapopulations within landscape linear elements. Maintenance of populations' connectivity through pollen and seed dispersal is a key factor in species persistence in the face of substantial habitat loss. The goals of this study were to investigate the potential corridor role of ditches and to identify the landscape components that significantly impact patterns of gene flow among remnant populations. Using microsatellite loci, we explored the spatial genetic structure of two hydrochorous wetland plants exhibiting contrasting local abundance and different habitat requirements: the rare and regionally protected Oenanthe aquatica and the more commonly distributed Lycopus europaeus, in an 83 km2 agricultural lowland located in northern France. Both species exhibited a significant spatial genetic structure, along with substantial levels of genetic differentiation, especially for L. europaeus, which also expressed high levels of inbreeding. Isolation-by-distance analysis revealed enhanced gene flow along ditches, indicating their key role in effective seed and pollen dispersal. Our data also suggested that the configuration of the ditch network and the landscape elements significantly affected population genetic structure, with (i) species-specific scale effects on the genetic neighborhood and (ii) detrimental impact of human ditch management on genetic diversity, especially for O. aquatica. Altogether, these findings highlighted the key role of ditches in the maintenance of plant biodiversity in intensive agricultural landscapes with few remnant wetland habitats. PMID:26486611

The multifunctional nuclear pore complex: a platform for controlling gene expression

PubMed Central

Ptak, Christopher; Aitchison, John D.; Wozniak, Richard W.

2014-01-01

In addition to their established roles in nucleocytoplasmic transport, the intimate association of nuclear pore complexes (NPCs) with chromatin has long led to speculation that these structures influence peripheral chromatin structure and regulate gene expression. These ideas have their roots in morphological observations, however recent years have seen the identification of physical interactions between NPCs, chromatin, and the transcriptional machinery. Key insights into the molecular functions of specific NPC proteins have uncovered roles for these proteins in transcriptional activation and elongation, mRNA processing, as well as chromatin structure and localization. Here, we review recent studies that provide further molecular detail on the role of specific NPC components as distinct platforms for these chromatin dependent processes. PMID:24657998

2016 Summer Series - Kenneth Cheung: Building Blocks for Aerospace Structures

NASA Image and Video Library

2016-06-16

Strong, ultra-lightweight materials are expected to play a key role in the design of future aircraft and space vehicles. Lower structural mass leads to improved performance, maneuverability, efficiency, range and payload capacity. Dr. Kenneth Cheung is developing cellular composite building blocks, or digital materials, to create transformable aerostructures. In his presentation, Dr. Cheung will discuss the implications of the digital materials and morphing structures.

The relationship between structured and free play in the development of a mentally handicapped child: a case study.

PubMed

Hewson, S; McConkey, R; Jeffree, D

1980-01-01

This case study provides an individual illustration of the work of the Parental Involvement Project. A key feature of the approach used was the structured play situation. Thus, the case study also serves to demonstrate the role of structured play, and its relation to free play, in the development of a young, mentally handicapped child.

Structural and Biochemical Characterization of a Copper-Binding Mutant of the Organomercurial Lyase MerB: Insight into the Key Role of the Active Site Aspartic Acid in Hg-Carbon Bond Cleavage and Metal Binding Specificity.

PubMed

Wahba, Haytham M; Lecoq, Lauriane; Stevenson, Michael; Mansour, Ahmed; Cappadocia, Laurent; Lafrance-Vanasse, Julien; Wilkinson, Kevin J; Sygusch, Jurgen; Wilcox, Dean E; Omichinski, James G

2016-02-23

In bacterial resistance to mercury, the organomercurial lyase (MerB) plays a key role in the detoxification pathway through its ability to cleave Hg-carbon bonds. Two cysteines (C96 and C159; Escherichia coli MerB numbering) and an aspartic acid (D99) have been identified as the key catalytic residues, and these three residues are conserved in all but four known MerB variants, where the aspartic acid is replaced with a serine. To understand the role of the active site serine, we characterized the structure and metal binding properties of an E. coli MerB mutant with a serine substituted for D99 (MerB D99S) as well as one of the native MerB variants containing a serine residue in the active site (Bacillus megaterium MerB2). Surprisingly, the MerB D99S protein copurified with a bound metal that was determined to be Cu(II) from UV-vis absorption, inductively coupled plasma mass spectrometry, nuclear magnetic resonance, and electron paramagnetic resonance studies. X-ray structural studies revealed that the Cu(II) is bound to the active site cysteine residues of MerB D99S, but that it is displaced following the addition of either an organomercurial substrate or an ionic mercury product. In contrast, the B. megaterium MerB2 protein does not copurify with copper, but the structure of the B. megaterium MerB2-Hg complex is highly similar to the structure of the MerB D99S-Hg complexes. These results demonstrate that the active site aspartic acid is crucial for both the enzymatic activity and metal binding specificity of MerB proteins and suggest a possible functional relationship between MerB and its only known structural homologue, the copper-binding protein NosL.

Revealing the Role of Microbes in Controlling Contaminants

ScienceCinema

Williams, Kenneth Hurst

2018-05-11

In Rifle, Colorado, Berkeley Lab earth scientist, Kenneth Hurst Williams, highlights the role subsurface microbial communities can play in controlling the flow of contaminants in groundwater. The DOE Joint Genome Institute is a key collaborator in the research. Williams is Component Lead of Watershed Structure and Controls within Berkeley Lab's Genomes-to-Watershed Scientific Focus Area.

Revealing the Role of Microbes in Controlling Contaminants

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

Williams, Kenneth Hurst

2015-04-02

In Rifle, Colorado, Berkeley Lab earth scientist, Kenneth Hurst Williams, highlights the role subsurface microbial communities can play in controlling the flow of contaminants in groundwater. The DOE Joint Genome Institute is a key collaborator in the research. Williams is Component Lead of Watershed Structure and Controls within Berkeley Lab's Genomes-to-Watershed Scientific Focus Area.

Career Survival: Strategic Job and Role Planning. Pfeiffer Career Series.

ERIC Educational Resources Information Center

Schein, Edgar H.

This book was designed to help managers and employees to decipher the two crucial elements in work design and human resource planning: the role network that surrounds every position and the key stakeholders whose expectations define the essence of the job. It provides a structured process for analyzing one's own job as well as the jobs of…

A qualitative study of the role of dental therapy in New Zealand.

PubMed

Tane, Helen R

2009-09-01

To investigate the role of the dental therapy profession in New Zealand, identifying the foundation of the profession, and the influences that have shaped its role. Qualitative study incorporating transcripts from oral archives, national questionnaires, and semi-structured interviews with key people of influence among the oral health professions. A selection of data was ordered into a written sequence and presented, to demonstrate key influencing factors in the introduction, training and work of New Zealand's dental nurses. Education for the dental therapy profession was preceded by the school dental nurse vocation and, despite the intention for the dental nurse's role to be one of 'forestalling disease' and 'prevention', the eventual role was very different. The study provides evidence of the valuable role of Dental Therapy in New Zealand's public health sector, but whether the role has been utilised most effectively is questionable, particularly when considering the original objectives that were given when the School Dental Nurse concept was first introduced.

A Study of the Structure and Content of Principal Selection Interviews in Pennsylvania

ERIC Educational Resources Information Center

Weber, Elizabeth A.

2012-01-01

The principal plays a key role in student success. The employment interview is a critical element in the principal selection process. This study examined the interview structure and the content of the interview questions that districts used in their principal search for the 2011-2012 school year. The research-based practices for interview…

The Role of Structural Extracellular Matrix Proteins in Urothelial Bladder Cancer (Review)

PubMed Central

Brunner, Andrea; Tzankov, Alexandar

2007-01-01

The extracellular matrix (ECM) plays a key role in the modulation of cancer cell invasion. In urothelial carcinoma of the bladder (UC) the role of ECM proteins has been widely studied. The mechanisms, which are involved in the development of invasion, progression and generalization, are complex, depending on the interaction of ECM proteins with each other as well as with cancer cells. The following review will focus on the pathogenetic role and prognostic value of structural proteins, such as laminins, collagens, fibronectin (FN), tenascin (Tn-C) and thrombospondin 1 (TSP1) in UC. In addition, the role of integrins mediating the interaction of ECM molecules and cancer cells will be addressed, since integrin-mediated FN, Tn-C and TSP1 interactions seem to play an important role during tumor cell invasion and angiogenesis. PMID:19662222

Density functional study of molecular interactions in secondary structures of proteins.

PubMed

Takano, Yu; Kusaka, Ayumi; Nakamura, Haruki

2016-01-01

Proteins play diverse and vital roles in biology, which are dominated by their three-dimensional structures. The three-dimensional structure of a protein determines its functions and chemical properties. Protein secondary structures, including α-helices and β-sheets, are key components of the protein architecture. Molecular interactions, in particular hydrogen bonds, play significant roles in the formation of protein secondary structures. Precise and quantitative estimations of these interactions are required to understand the principles underlying the formation of three-dimensional protein structures. In the present study, we have investigated the molecular interactions in α-helices and β-sheets, using ab initio wave function-based methods, the Hartree-Fock method (HF) and the second-order Møller-Plesset perturbation theory (MP2), density functional theory, and molecular mechanics. The characteristic interactions essential for forming the secondary structures are discussed quantitatively.

E-cadherin junction formation involves an active kinetic nucleation process

PubMed Central

Biswas, Kabir H.; Hartman, Kevin L.; Yu, Cheng-han; Harrison, Oliver J.; Song, Hang; Smith, Adam W.; Huang, William Y. C.; Lin, Wan-Chen; Guo, Zhenhuan; Padmanabhan, Anup; Troyanovsky, Sergey M.; Dustin, Michael L.; Shapiro, Lawrence; Honig, Barry; Zaidel-Bar, Ronen; Groves, Jay T.

2015-01-01

Epithelial (E)-cadherin-mediated cell−cell junctions play important roles in the development and maintenance of tissue structure in multicellular organisms. E-cadherin adhesion is thus a key element of the cellular microenvironment that provides both mechanical and biochemical signaling inputs. Here, we report in vitro reconstitution of junction-like structures between native E-cadherin in living cells and the extracellular domain of E-cadherin (E-cad-ECD) in a supported membrane. Junction formation in this hybrid live cell-supported membrane configuration requires both active processes within the living cell and a supported membrane with low E-cad-ECD mobility. The hybrid junctions recruit α-catenin and exhibit remodeled cortical actin. Observations suggest that the initial stages of junction formation in this hybrid system depend on the trans but not the cis interactions between E-cadherin molecules, and proceed via a nucleation process in which protrusion and retraction of filopodia play a key role. PMID:26290581

E-cadherin junction formation involves an active kinetic nucleation process

DOE PAGES

Biswas, Kabir H.; Hartman, Kevin L.; Yu, Cheng -han; ...

2015-08-19

Epithelial (E)-cadherin-mediated cell–cell junctions play important roles in the development and maintenance of tissue structure in multicellular organisms. E-cadherin adhesion is thus a key element of the cellular microenvironment that provides both mechanical and biochemical signaling inputs. Here, we report in vitro reconstitution of junction-like structures between native E-cadherin in living cells and the extracellular domain of E-cadherin in a supported membrane. Junction formation in this hybrid live cell-supported membrane configuration requires both active processes within the living cell and a supported membrane with low E-cad-ECD mobility. The hybrid junctions recruit α-catenin and exhibit remodeled cortical actin. Observations suggest thatmore » the initial stages of junction formation in this hybrid system depend on the trans but not the cis interactions between E-cadherin molecules, and proceed via a nucleation process in which protrusion and retraction of filopodia play a key role.« less

E-cadherin junction formation involves an active kinetic nucleation process

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

Biswas, Kabir H.; Hartman, Kevin L.; Yu, Cheng -han

Epithelial (E)-cadherin-mediated cell–cell junctions play important roles in the development and maintenance of tissue structure in multicellular organisms. E-cadherin adhesion is thus a key element of the cellular microenvironment that provides both mechanical and biochemical signaling inputs. Here, we report in vitro reconstitution of junction-like structures between native E-cadherin in living cells and the extracellular domain of E-cadherin in a supported membrane. Junction formation in this hybrid live cell-supported membrane configuration requires both active processes within the living cell and a supported membrane with low E-cad-ECD mobility. The hybrid junctions recruit α-catenin and exhibit remodeled cortical actin. Observations suggest thatmore » the initial stages of junction formation in this hybrid system depend on the trans but not the cis interactions between E-cadherin molecules, and proceed via a nucleation process in which protrusion and retraction of filopodia play a key role.« less

Tandem Repeats in Proteins: Prediction Algorithms and Biological Role.

PubMed

Pellegrini, Marco

2015-01-01

Tandem repetitions in protein sequence and structure is a fascinating subject of research which has been a focus of study since the late 1990s. In this survey, we give an overview on the multi-faceted aspects of research on protein tandem repeats (PTR for short), including prediction algorithms, databases, early classification efforts, mechanisms of PTR formation and evolution, and synthetic PTR design. We also touch on the rather open issue of the relationship between PTR and flexibility (or disorder) in proteins. Detection of PTR either from protein sequence or structure data is challenging due to inherent high (biological) signal-to-noise ratio that is a key feature of this problem. As early in silico analytic tools have been key enablers for starting this field of study, we expect that current and future algorithmic and statistical breakthroughs will have a high impact on the investigations of the biological role of PTR.

Investigation of Pb species in soils, celery and duckweed by synchrotron radiation X-ray absorption near-edge structure spectrometry

NASA Astrophysics Data System (ADS)

Luo, Liqiang; Shen, Yating; Liu, Jian; Zeng, Yuan

2016-08-01

The Pb species play a key role in its translocation in biogeochemical cycles. Soils, sediments and plants were collected from farmlands around Pb mines, and the Pb species in them was identified by X-ray absorption near-edge structure spectrometry. In soils, Pb5(PO4)3Cl and Pb3(PO4)2 were detected, and in sediments, Pb-fulvic acids (FAs) complex was identified. A Pb complex with FA fragments was also detected in celery samples. We found that (1) different Pb species were present in soils and sediments; (2) the Pb species in celery, which was grown in sediments, was different from the species present in duckweed, which grew in water; and (3) a Pb-FA-like compound was present in celery roots. The newly identified Pb species, the Pb-FA-like compound, may play a key role in Pb tolerance and translocation within plants.

Left Inferior Frontal Cortex and Syntax: Function, Structure and Behaviour in Patients with Left Hemisphere Damage

ERIC Educational Resources Information Center

Tyler, Lorraine K.; Marslen-Wilson, William D.; Randall, Billi; Wright, Paul; Devereux, Barry J.; Zhuang, Jie; Papoutsi, Marina; Stamatakis, Emmanuel A.

2011-01-01

For the past 150 years, neurobiological models of language have debated the role of key brain regions in language function. One consistently debated set of issues concern the role of the left inferior frontal gyrus in syntactic processing. Here we combine measures of functional activity, grey matter integrity and performance in patients with left…

Key stakeholder perceptions regarding acute care psychiatry in distressed publicly funded mental health care markets.

PubMed

Frueh, B Christopher; Grubaugh, Anouk L; Lo Sasso, Anthony T; Jones, Walter J; Oldham, John M; Lindrooth, Richard C

2012-01-01

The role of acute care inpatient psychiatry, public and private, has changed dramatically since the 1960s, especially as recent market forces affecting the private sector have had ripple effects on publicly funded mental health care. Key stakeholders' experiences, perceptions, and opinions regarding the role of acute care psychiatry in distressed markets of publicly funded mental health care were examined. A qualitative research study was conducted using semi-structured thematic interviews with 52 senior mental health system administrators, clinical directors and managers, and nonclinical policy specialists. Participants were selected from markets in six regions of the United States that experienced recent significant closures of acute care psychiatric beds. Qualitative data analyses yielded findings that clustered around three sets of higher order themes: structure of care, service delivery barriers, and outcomes. Structure of care suggests that acute care psychiatry is seen as part of a continuum of services; service delivery barriers inhibit effective delivery of services and are perceived to include economic, regulatory, and political factors; outcomes include fragmentation of mental health care services across the continuum, the shift of mental health care to the criminal justice system, and market-specific issues affecting mental health care. Findings delineate key stakeholders' perceptions regarding the role acute care psychiatry plays in the continuum of care for publicly funded mental health and suggest that public mental health care is inefficacious. Results carry implications for policy makers regarding strategies/policies to improve optimal utilization of scarce resources for mental health care, including greater focus on psychotherapy.

Key stakeholder perceptions regarding acute care psychiatry in distressed publicly funded mental health care markets

PubMed Central

Frueh, B. Christopher; Grubaugh, Anouk L.; Lo Sasso, Anthony T.; Jones, Walter J.; Oldham, John M.; Lindrooth, Richard C.

2017-01-01

The role of acute care inpatient psychiatry, public and private, has changed dramatically since the 1960s, especially as recent market forces affecting the private sector have had ripple effects on publicly funded mental health care. Key stakeholders’ experiences, perceptions, and opinions regarding the role of acute care psychiatry in distressed markets of publicly funded mental health care were examined. A qualitative research study was conducted using semi-structured thematic interviews with 52 senior mental health system administrators, clinical directors and managers, and nonclinical policy specialists. Participants were selected from markets in six regions of the United States that experienced recent significant closures of acute care psychiatric beds. Qualitative data analyses yielded findings that clustered around three sets of higher order themes: structure of care, service delivery barriers, and outcomes. Structure of care suggests that acute care psychiatry is seen as part of a continuum of services; service delivery barriers inhibit effective delivery of services and are perceived to include economic, regulatory, and political factors; outcomes include fragmentation of mental health care services across the continuum, the shift of mental health care to the criminal justice system, and market-specific issues affecting mental health care. Findings delineate key stakeholders’ perceptions regarding the role acute care psychiatry plays in the continuum of care for publicly funded mental health and suggest that public mental health care is inefficacious. Results carry implications for policy makers regarding strategies/policies to improve optimal utilization of scarce resources for mental health care, including greater focus on psychotherapy. PMID:22409204

Crystal structure of isoflavone reductase from alfalfa (Medicago sativa L.).

PubMed

Wang, Xiaoqiang; He, Xianzhi; Lin, Jianqiao; Shao, Hui; Chang, Zhenzhan; Dixon, Richard A

2006-05-19

Isoflavonoids play important roles in plant defense and exhibit a range of mammalian health-promoting activities. Isoflavone reductase (IFR) specifically recognizes isoflavones and catalyzes a stereospecific NADPH-dependent reduction to (3R)-isoflavanone. The crystal structure of Medicago sativa IFR with deletion of residues 39-47 has been determined at 1.6A resolution. Structural analysis, molecular modeling and docking, and comparison with the structures of other NADPH-dependent enzymes, defined the putative binding sites for co-factor and substrate and potential key residues for enzyme activity and substrate specificity. Further mutagenesis has confirmed the role of Lys144 as a catalytic residue. This study provides a structural basis for understanding the enzymatic mechanism and substrate specificity of IFRs as well as the functions of IFR-like proteins.

The Role of Biotin in Bacterial Physiology and Virulence: a Novel Antibiotic Target for Mycobacterium tuberculosis.

PubMed

Salaemae, Wanisa; Booker, Grant W; Polyak, Steven W

2016-04-01

Biotin is an essential cofactor for enzymes present in key metabolic pathways such as fatty acid biosynthesis, replenishment of the tricarboxylic acid cycle, and amino acid metabolism. Biotin is synthesized de novo in microorganisms, plants, and fungi, but this metabolic activity is absent in mammals, making biotin biosynthesis an attractive target for antibiotic discovery. In particular, biotin biosynthesis plays important metabolic roles as the sole source of biotin in all stages of the Mycobacterium tuberculosis life cycle due to the lack of a transporter for scavenging exogenous biotin. Biotin is intimately associated with lipid synthesis where the products form key components of the mycobacterial cell membrane that are critical for bacterial survival and pathogenesis. In this review we discuss the central role of biotin in bacterial physiology and highlight studies that demonstrate the importance of its biosynthesis for virulence. The structural biology of the known biotin synthetic enzymes is described alongside studies using structure-guided design, phenotypic screening, and fragment-based approaches to drug discovery as routes to new antituberculosis agents.

Learning Higher-Order Generalizations through Free Play: Evidence from 2- and 3-Year-Old Children

ERIC Educational Resources Information Center

Sim, Zi L.; Xu, Fei

2017-01-01

Constructivist views of cognitive development often converge on 2 key points: (1) the child's goal is to build large conceptual structures for understanding the world, and (2) the child plays an active role in developing these structures. While previous research has demonstrated that young children show a precocious capacity for concept and theory…

Hippocampal Structure and Human Cognition: Key Role of Spatial Processing and Evidence Supporting the Efficiency Hypothesis in Females

ERIC Educational Resources Information Center

Colom, Roberto; Stein, Jason L.; Rajagopalan, Priya; Martinez, Kenia; Hermel, David; Wang, Yalin; Alvarez-Linera, Juan; Burgaleta, Miguel; Quiroga, Ma. Angeles; Shih, Pei Chun; Thompson, Paul M.

2013-01-01

Here we apply a method for automated segmentation of the hippocampus in 3D high-resolution structural brain MRI scans. One hundred and four healthy young adults completed twenty one tasks measuring abstract, verbal, and spatial intelligence, along with working memory, executive control, attention, and processing speed. After permutation tests…

Forward Looking: Structural Change and Institutions in Highestincome Countries and Globally

ERIC Educational Resources Information Center

Ahamer, Gilbert; Mayer, Johannes

2013-01-01

Purpose: Structural economic shifts are a key sign of development in all stages globally; and these shifts may also result in the changing roles of institutions. The purpose of this paper is to quantitatively analyse trends that may be used for so-called forward looking and makes use of them to recommend strategies for reorganising institutions.…

Certificate Structure Study: Do Stackable Certificates Really "Add" up to a Degree? Research Report 17-2

ERIC Educational Resources Information Center

Washington State Board for Community and Technical Colleges, 2017

2017-01-01

The purpose of this study is to answer key questions about the structure of certificates and their function in employability and degree attainment in the Washington State Community and Technical College (CTC) System. Specifically, this study addresses the following: (1) Do certificates play a role in helping students progress along career pathways…

Redesigning a Ministry of Health's organizational structure: exploring implementation challenges through Botswana's experiences.

PubMed

Seitio-Kgokgwe, Onalenna; Gauld, Robin D C; Hill, Philip C; Barnett, Pauline

2016-04-01

The Botswana's Ministry of Health redesigned and adopted a new organizational structure in 2005, which was poorly implemented. This article explores factors that influenced the implementation of this organizational structure. This article draws from data collected through in-depth interviews with 54 purposively selected key informants comprising policy makers, senior managers and staff of the Ministry of Health (N = 40) and senior officers from various stakeholder organizations (N = 14). Participants generally felt that the review of the Ministry of Health organizational structure was important. The previous structure was considered obsolete with fragmented functions that limited the overall performance of the health system. The new organizational structure was viewed to be aligned to current national priorities with potential to positively influence performance. Some key weaknesses identified included lack of consultation and information sharing with workers during the restructuring process, which affected the understanding of their new roles, failure to mobilize key resources to support implementation of the new structure and inadequate monitoring of the implementation process. Redesigning an organizational structure is a major change. There is a need for effective and sustained leadership to plan, direct, coordinate, monitor and evaluate the implementation phase of the reform. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Crystal structure of Streptococcus pneumoniae pneumolysin provides key insights into early steps of pore formation

PubMed Central

Lawrence, Sara L.; Feil, Susanne C.; Morton, Craig J.; Farrand, Allison J.; Mulhern, Terrence D.; Gorman, Michael A.; Wade, Kristin R.; Tweten, Rodney K.; Parker, Michael W.

2015-01-01

Pore-forming proteins are weapons often used by bacterial pathogens to breach the membrane barrier of target cells. Despite their critical role in infection important structural aspects of the mechanism of how these proteins assemble into pores remain unknown. Streptococcus pneumoniae is the world’s leading cause of pneumonia, meningitis, bacteremia and otitis media. Pneumolysin (PLY) is a major virulence factor of S. pneumoniae and a target for both small molecule drug development and vaccines. PLY is a member of the cholesterol-dependent cytolysins (CDCs), a family of pore-forming toxins that form gigantic pores in cell membranes. Here we present the structure of PLY determined by X-ray crystallography and, in solution, by small-angle X-ray scattering. The crystal structure reveals PLY assembles as a linear oligomer that provides key structural insights into the poorly understood early monomer-monomer interactions of CDCs at the membrane surface. PMID:26403197

Key functional role of the optical properties of coral skeletons in coral ecology and evolution.

PubMed

Enríquez, Susana; Méndez, Eugenio R; Hoegh-Guldberg, Ove; Iglesias-Prieto, Roberto

2017-04-26

Multiple scattering of light on coral skeleton enhances light absorption efficiency of coral symbionts and plays a key role in the regulation of their internal diffuse light field. To understand the dependence of this enhancement on skeleton meso- and macrostructure, we analysed the scattering abilities of naked coral skeletons for 74 Indo-Pacific species. Sensitive morphotypes to thermal and light stress, flat-extraplanate and branching corals, showed the most efficient structures, while massive-robust species were less efficient. The lowest light-enhancing scattering abilities were found for the most primitive colonial growth form: phaceloid. Accordingly, the development of highly efficient light-collecting structures versus the selection of less efficient but more robust holobionts to cope with light stress may constitute a trade-off in the evolution of modern symbiotic scleractinian corals, characterizing two successful adaptive solutions. The coincidence of the most important structural modifications with epitheca decline supports the importance of the enhancement of light transmission across coral skeleton in modern scleractinian diversification, and the central role of these symbioses in the design and optimization of coral skeleton. Furthermore, the same ability that lies at the heart of the success of symbiotic corals as coral-reef-builders can also explain the 'Achilles's heel' of these symbioses in a warming ocean. © 2017 The Author(s).

Biotemplated materials for sustainable energy and environment: current status and challenges.

PubMed

Zhou, Han; Fan, Tongxiang; Zhang, Di

2011-10-17

Materials science will play a key role in the further development of emerging solutions for the increasing problems of energy and environment. Materials found in nature have many inspiring structures, such as hierarchical organizations, periodic architectures, or nanostructures, that endow them with amazing functions, such as energy harvesting and conversion, antireflection, structural coloration, superhydrophobicity, and biological self-assembly. Biotemplating is an effective strategy to obtain morphology-controllable materials with structural specificity, complexity, and related unique functions. Herein, we highlight the synthesis and application of biotemplated materials for six key areas of energy and environment technologies, namely, photocatalytic hydrogen evolution, CO(2) reduction, solar cells, lithium-ion batteries, photocatalytic degradation, and gas/vapor sensing. Although the applications differ from each other, a common fundamental challenge is to realize optimum structures for improved performances. We highlight the role of four typical structures derived from biological systems exploited to optimize properties: hierarchical (porous) structures, periodic (porous) structures, hollow structures, and nanostructures. We also provide examples of using biogenic elements (e.g., C, Si, N, I, P, S) for the creation of active materials. Finally, we disscuss the challenges of achieving the desired performance for large-scale commercial applications and provide some useful prototypes from nature for the biomimetic design of new materials or systems. The emphasis is mainly focused on the structural effects and compositional utilization of biotemplated materials. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Computational screening of organic polymer dielectrics for novel accelerator technologies

DOE PAGES

Pilania, Ghanshyam; Weis, Eric; Walker, Ethan M.; ...

2018-06-18

The use of infrared lasers to power accelerating dielectric structures is a developing area of research. Within this technology, the choice of the dielectric material forming the accelerating structures, such as the photonic band gap (PBG) structures, is dictated by a range of interrelated factors including their dielectric and optical properties, amenability to photo-polymerization, thermochemical stability and other target performance metrics of the particle accelerator. In this direction, electronic structure theory aided computational screening and design of dielectric materials can play a key role in identifying potential candidate materials with the targeted functionalities to guide experimental synthetic efforts. In anmore » attempt to systematically understand the role of chemistry in controlling the electronic structure and dielectric properties of organic polymeric materials, here we employ empirical screening and density functional theory (DFT) computations, as a part of our multi-step hierarchal screening strategy. Our DFT based analysis focused on the bandgap, dielectric permittivity, and frequency-dependent dielectric losses due to lattice absorption as key properties to down-select promising polymer motifs. In addition to the specific application of dielectric laser acceleration, the general methodology presented here is deemed to be valuable in the design of new insulators with an attractive combination of dielectric properties.« less

Executing on Integration: The Key to Success in Mergers and Acquisitions.

PubMed

Bradley, Carol

2016-01-01

Health care mergers and acquisitions require a clearly stated vision and exquisite planning of integration activities to provide the best possible conditions for a successful transaction. During the due diligence process, key steps can be taken to create a shared vision and a plan to inspire confidence and build enthusiasm for all stakeholders. Integration planning should include a defined structure, roles and responsibilities, as well as a method for evaluation.

The role of non timber forest products: a case study of gatherers in the eastern United States

Treesearch

Siri Doble; Marla Emery

2001-01-01

Non Timber Forest Products (NTFPs) play a key role in the lives and livelihoods of rural residents in or near forested areas. Consequently, organizations concerned with rural development have begun to look toward NTFPs as an opportunity for rural economic development. Concerned with the potential implications for the social and ecological structures that support NTFP...

Correlation between the hierarchical structures and nanomechanical properties of amyloid fibrils

NASA Astrophysics Data System (ADS)

Lee, Gyudo; Lee, Wonseok; Baik, Seunghyun; Kim, Yong Ho; Eom, Kilho; Kwon, Taeyun

2018-07-01

Amyloid fibrils have recently been highlighted due to their excellent mechanical properties, which not only play a role in their biological functions but also imply their applications in biomimetic material design. Despite recent efforts to unveil how the excellent mechanical properties of amyloid fibrils originate, it has remained elusive how the anisotropic nanomechanical properties of hierarchically structured amyloid fibrils are determined. Here, we characterize the anisotropic nanomechanical properties of hierarchically structured amyloid fibrils using atomic force microscopy experiments and atomistic simulations. It is shown that the hierarchical structure of amyloid fibrils plays a crucial role in determining their radial elastic property but does not make any effect on their bending elastic property. This is attributed to the role of intermolecular force acting between the filaments (constituting the fibril) on the radial elastic modulus of amyloid fibrils. Our finding illustrates how the hierarchical structure of amyloid fibrils encodes their anisotropic nanomechanical properties. Our study provides key design principles of amyloid fibrils, which endow valuable insight into the underlying mechanisms of amyloid mechanics.

Global structure of forked DNA in solution revealed by high-resolution single-molecule FRET.

PubMed

Sabir, Tara; Schröder, Gunnar F; Toulmin, Anita; McGlynn, Peter; Magennis, Steven W

2011-02-09

Branched DNA structures play critical roles in DNA replication, repair, and recombination in addition to being key building blocks for DNA nanotechnology. Here we combine single-molecule multiparameter fluorescence detection and molecular dynamics simulations to give a general approach to global structure determination of branched DNA in solution. We reveal an open, planar structure of a forked DNA molecule with three duplex arms and demonstrate an ion-induced conformational change. This structure will serve as a benchmark for DNA-protein interaction studies.

Strategies for Supporting Physician-Scientists in Faculty Roles: A Narrative Review With Key Informant Consultations.

PubMed

Lingard, Lorelei; Zhang, Peter; Strong, Michael; Steele, Margaret; Yoo, John; Lewis, James

2017-10-01

Physician-scientists are a population in decline globally. Solutions to reverse this decline often have focused on the training pipeline. Less attention has been paid to reducing attrition post training, when physician-scientists take up faculty roles. However, this period is a known time of vulnerability because of the pressures of clinical duties and the long timeline to securing independent research funding. This narrative review explored existing knowledge regarding how best to support physician-scientists for success in their faculty roles. The authors searched the Medline, Embase, ERIC, and Cochrane Library databases for articles published from 2000 to 2016 on this topic and interviewed key informants in 2015 to solicit their input on the review results. The authors reviewed 78 articles and interviewed 16 key informants. From the literature, they developed a framework of organizational (facilitate mentorship, foster community, value the physician-scientist role, minimize financial barriers) and individual (develop professional and research skills) strategies for supporting physician-scientists. They also outlined key knowledge gaps representing topics either rarely or never addressed in the reviewed articles (percent research time, structural hypocrisy, objective assessment, group metrics, professional identity). The key informants confirmed the identified strategies and discussed how the gaps were particularly important and impactful. This framework offers a basis for assessing an organization's existing support strategies, identifying outstanding needs, and developing targeted programming. The identified gaps require attention, as they threaten to undermine the benefits of existing support strategies.

Social Networks and Community-Based Natural Resource Management

NASA Astrophysics Data System (ADS)

Lauber, T. Bruce; Decker, Daniel J.; Knuth, Barbara A.

2008-10-01

We conducted case studies of three successful examples of collaborative, community-based natural resource conservation and development. Our purpose was to: (1) identify the functions served by interactions within the social networks of involved stakeholders; (2) describe key structural properties of these social networks; and (3) determine how these structural properties varied when the networks were serving different functions. The case studies relied on semi-structured, in-depth interviews of 8 to 11 key stakeholders at each site who had played a significant role in the collaborative projects. Interview questions focused on the roles played by key stakeholders and the functions of interactions between them. Interactions allowed the exchange of ideas, provided access to funding, and enabled some stakeholders to influence others. The exchange of ideas involved the largest number of stakeholders, the highest percentage of local stakeholders, and the highest density of interactions. Our findings demonstrated the value of tailoring strategies for involving stakeholders to meet different needs during a collaborative, community-based natural resource management project. Widespread involvement of local stakeholders may be most appropriate when ideas for a project are being developed. During efforts to exert influence to secure project approvals or funding, however, involving specific individuals with political connections or influence on possible sources of funds may be critical. Our findings are consistent with past work that has postulated that social networks may require specific characteristics to meet different needs in community-based environmental management.

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

Bosserman, Mary A.; Downey, Theresa; Noinaj, Nicholas

Baeyer–Villiger monooxygenases (BVMOs) have been shown to play key roles for the biosynthesis of important natural products. MtmOIV, a homodimeric FAD- and NADPH-dependent BVMO, catalyzes the key frame-modifying steps of the mithramycin biosynthetic pathway, including an oxidative C–C bond cleavage, by converting its natural substrate premithramycin B into mithramycin DK, the immediate precursor of mithramycin. The drastically improved protein structure of MtmOIV along with the high-resolution structure of MtmOIV in complex with its natural substrate premithramycin B are reported here, revealing previously undetected key residues that are important for substrate recognition and catalysis. Kinetic analyses of selected mutants allowed usmore » to probe the substrate binding pocket of MtmOIV and also to discover the putative NADPH binding site. This is the first substrate-bound structure of MtmOIV providing new insights into substrate recognition and catalysis, which paves the way for the future design of a tailored enzyme for the chemo-enzymatic preparation of novel mithramycin analogues.« less

Service line structure and decision-maker attention in three health systems: Implications for patient-centered care.

PubMed

Louis, Christopher J; Clark, Jonathan R; Gray, Barbara; Brannon, Diane; Parker, Victoria

2017-06-15

Scholars have noted a disconnect between the level at which structure is typically examined (the organization) and the level at which the relevant coordination takes place (service delivery). Accordingly, our understanding of the role structure plays in care coordination is limited. In this article, we explore service line structure, with an aim of advancing our understanding of the role service line structure plays in producing coordinated, patient-centered care. We do so by giving special attention to the cognitive roots of patient-centeredness. Our exploratory study relied on comparative case studies of the breast cancer service lines in three health systems. Nonprobability discriminative snowball sampling was used to identify the final sample of key informants. We employed a grounded approach to analyzing and interpreting the data. We found substantial variation across the three service lines in terms of their structure. We also found corresponding variation across the three case sites in terms of where informant attention was primarily focused in the process of coordinating care. Drawing on the attention-based view of the firm, our results draw a clear connection between structural characteristics and the dominant focus of attention (operational tactics, provider roles and relationships, or patient needs and engagement) in health care service lines. Our exploratory results suggest that service line structures influence attention in two ways: (a) by regulating the type and intensity of the problems facing service line participants and (b) by encouraging (or discouraging) a shared purpose around patient needs. Patient-centered attention-a precursor to coordinated, patient-centered care-depends on the internal choices organizations make around service line structure. Moreover, a key task for organizational and service line leaders is to structure service lines to create a context that minimizes distractions and enables care providers to focus their attention on the needs of their patients.

Homogalacturonan-modifying enzymes: structure, expression, and roles in plants

PubMed Central

Sénéchal, Fabien; Wattier, Christopher; Rustérucci, Christine; Pelloux, Jérôme

2014-01-01

Understanding the changes affecting the plant cell wall is a key element in addressing its functional role in plant growth and in the response to stress. Pectins, which are the main constituents of the primary cell wall in dicot species, play a central role in the control of cellular adhesion and thereby of the rheological properties of the wall. This is likely to be a major determinant of plant growth. How the discrete changes in pectin structure are mediated is thus a key issue in our understanding of plant development and plant responses to changes in the environment. In particular, understanding the remodelling of homogalacturonan (HG), the most abundant pectic polymer, by specific enzymes is a current challenge in addressing its fundamental role. HG, a polymer that can be methylesterified or acetylated, can be modified by HGMEs (HG-modifying enzymes) which all belong to large multigenic families in all species sequenced to date. In particular, both the degrees of substitution (methylesterification and/or acetylation) and polymerization can be controlled by specific enzymes such as pectin methylesterases (PMEs), pectin acetylesterases (PAEs), polygalacturonases (PGs), or pectate lyases-like (PLLs). Major advances in the biochemical and functional characterization of these enzymes have been made over the last 10 years. This review aims to provide a comprehensive, up to date summary of the recent data concerning the structure, regulation, and function of these fascinating enzymes in plant development and in response to biotic stresses. PMID:25056773

Commentary: Why Pharmaceutical Scientists in Early Drug Discovery Are Critical for Influencing the Design and Selection of Optimal Drug Candidates.

PubMed

Landis, Margaret S; Bhattachar, Shobha; Yazdanian, Mehran; Morrison, John

2018-01-01

This commentary reflects the collective view of pharmaceutical scientists from four different organizations with extensive experience in the field of drug discovery support. Herein, engaging discussion is presented on the current and future approaches for the selection of the most optimal and developable drug candidates. Over the past two decades, developability assessment programs have been implemented with the intention of improving physicochemical and metabolic properties. However, the complexity of both new drug targets and non-traditional drug candidates provides continuing challenges for developing formulations for optimal drug delivery. The need for more enabled technologies to deliver drug candidates has necessitated an even more active role for pharmaceutical scientists to influence many key molecular parameters during compound optimization and selection. This enhanced role begins at the early in vitro screening stages, where key learnings regarding the interplay of molecular structure and pharmaceutical property relationships can be derived. Performance of the drug candidates in formulations intended to support key in vivo studies provides important information on chemotype-formulation compatibility relationships. Structure modifications to support the selection of the solid form are also important to consider, and predictive in silico models are being rapidly developed in this area. Ultimately, the role of pharmaceutical scientists in drug discovery now extends beyond rapid solubility screening, early form assessment, and data delivery. This multidisciplinary role has evolved to include the practice of proactively taking part in the molecular design to better align solid form and formulation requirements to enhance developability potential.

Healthcare organizational performance: why changing the culture really matters. Commentary.

PubMed

Azzolini, Elena; Ricciardi, Walter; Gray, Muir

2018-01-01

An organization may be considered as having three components: a structure, systems and culture. Culture is the most difficult part of the organization to affect. After all, culture has the key role in impacting and improving organizational performance. The leadership of an organization and its key operations are paramount in shaping the culture. Leadership and organizational culture are inextricably intertwined. They are two sides of the same coin. Culture is a medium through which leadership travels and impacts organizational performance. If leaders are to fulfil the challenges of the 21st century, they must first understand the dynamics of culture and their role as sculptors through behavioural and cognitive ways.

Nurse practitioner integration: Qualitative experiences of the change management process.

PubMed

Lowe, Grainne; Plummer, Virginia; Boyd, Leanne

2018-04-30

The aim of this qualitative research was to explore perceptions of organisational change related to the integration of nurse practitioners from key nursing stakeholders. The ongoing delivery of effective and efficient patient services is reliant upon the development and sustainability of nurse practitioner roles. Examination of the factors contributing to the underutilization of nurse practitioner roles is crucial to inform future management policies. A change management theory is used to reveal the complexity involved. Qualitative interviews were undertaken using a purposive sampling strategy of key stakeholders. Thematic analysis was undertaken and key themes were correlated to the theoretical framework. The results confirm the benefits of nurse practitioner roles, but suggest organisational structures and embedded professional cultures present barriers to full role optimization. Complicated policy processes are creating barriers to the integration of nurse practitioner roles. The findings increase understanding of the links between strategic planning, human resource management, professional and organisational cultures, governance and politics in change management. Effective leadership drives the change process through the ability to align key components necessary for success. Sustainability of nurse practitioners relies on recognition of their full potential in the health care team. The results of this study highlight the importance of management and leadership in the promotion of advanced nursing skills and experience to better meet patient outcomes. The findings reinforce the potential of nurse practitioners to deliver patient centred, timely and efficient health care. © 2018 John Wiley & Sons Ltd.

The key role of the scaffold on the efficiency of dendrimer nanodrugs

PubMed Central

Caminade, Anne-Marie; Fruchon, Séverine; Turrin, Cédric-Olivier; Poupot, Mary; Ouali, Armelle; Maraval, Alexandrine; Garzoni, Matteo; Maly, Marek; Furer, Victor; Kovalenko, Valeri; Majoral, Jean-Pierre; Pavan, Giovanni M.; Poupot, Rémy

2015-01-01

Dendrimers are well-defined macromolecules whose highly branched structure is reminiscent of many natural structures, such as trees, dendritic cells, neurons or the networks of kidneys and lungs. Nature has privileged such branched structures for increasing the efficiency of exchanges with the external medium; thus, the whole structure is of pivotal importance for these natural networks. On the contrary, it is generally believed that the properties of dendrimers are essentially related to their terminal groups, and that the internal structure plays the minor role of an ‘innocent' scaffold. Here we show that such an assertion is misleading, using convergent information from biological data (human monocytes activation) and all-atom molecular dynamics simulations on seven families of dendrimers (13 compounds) that we have synthesized, possessing identical terminal groups, but different internal structures. This work demonstrates that the scaffold of nanodrugs strongly influences their properties, somewhat reminiscent of the backbone of proteins. PMID:26169490

Harnessing glycomics technologies: integrating structure with function for glycan characterization

PubMed Central

Robinson, Luke N.; Artpradit, Charlermchai; Raman, Rahul; Shriver, Zachary H.; Ruchirawat, Mathuros; Sasisekharan, Ram

2013-01-01

Glycans, or complex carbohydrates, are a ubiquitous class of biological molecules which impinge on a variety of physiological processes ranging from signal transduction to tissue development and microbial pathogenesis. In comparison to DNA and proteins, glycans present unique challenges to the study of their structure and function owing to their complex and heterogeneous structures and the dominant role played by multivalency in their sequence-specific biological interactions. Arising from these challenges, there is a need to integrate information from multiple complementary methods to decode structure-function relationships. Focusing on acidic glycans, we describe here key glycomics technologies for characterizing their structural attributes, including linkage, modifications, and topology, as well as for elucidating their role in biological processes. Two cases studies, one involving sialylated branched glycans and the other sulfated glycosaminoglycans, are used to highlight how integration of orthogonal information from diverse datasets enables rapid convergence of glycan characterization for development of robust structure-function relationships. PMID:22522536

The notochord: structure and functions.

PubMed

Corallo, Diana; Trapani, Valeria; Bonaldo, Paolo

2015-08-01

The notochord is an embryonic midline structure common to all members of the phylum Chordata, providing both mechanical and signaling cues to the developing embryo. In vertebrates, the notochord arises from the dorsal organizer and it is critical for proper vertebrate development. This evolutionary conserved structure located at the developing midline defines the primitive axis of embryos and represents the structural element essential for locomotion. Besides its primary structural function, the notochord is also a source of developmental signals that patterns surrounding tissues. Among the signals secreted by the notochord, Hedgehog proteins play key roles during embryogenesis. The Hedgehog signaling pathway is a central regulator of embryonic development, controlling the patterning and proliferation of a wide variety of organs. In this review, we summarize the current knowledge on notochord structure and functions, with a particular emphasis on the key developmental events that take place in vertebrates. Moreover, we discuss some genetic studies highlighting the phenotypic consequences of impaired notochord development, which enabled to understand the molecular basis of different human congenital defects and diseases.

Using the ICF to clarify team roles and demonstrate clinical reasoning in stroke rehabilitation.

PubMed

Tempest, Stephanie; McIntyre, Anne

2006-05-30

The International Classification of Functioning, Disability and Health (ICF) is advocated as a tool to structure rehabilitation and a universal language to aid communication, within the multi-disciplinary team (MDT). The ICF may also facilitate clarification of team roles and clinical reasoning for intervention. This article aims to explore both factors in stroke rehabilitation. Following a review of the literature, a summary was presented and discussed with clinicians working within stroke rehabilitation, to gather expert opinions. The discussions were informal, being part of service development and on-going education. The clinicians summarised key themes for the potential use of the ICF within clinical practice. Two key themes emerged from the literature and expert opinion for the potential use of the ICF in stroke rehabilitation: (i) to aid communication and structure service provision, (ii) to clarify team roles and aid clinical reasoning. Expert opinion was that clarification of team roles needs to occur at a local level due to the skill mix, particular interests, setting and staffing levels within individual teams. The ICF has the potential to demonstrate/facilitate clinical reasoning, especially when different MDT members are working on the same intervention. There is potential for the ICF to be used to clarify team roles and demonstrate clinical reasoning within stroke rehabilitation. Further experiential research is required to substantiate this view.

iThesis: Polly's project

ERIC Educational Resources Information Center

Conti, Alvaro

2013-01-01

This paper outlines an attempt to loosen the existing role and structure of the traditional "thesis" as the key undergraduate learning instrument within universities in Thailand. It does so by describing an exemplary project -- Polly's project - that uses technology to facilitate an exit from the "regulatory space" in which…

Effects of landscape and patch-level attributes on regional population persistence

EPA Science Inventory

Habitat patch size and isolation are often described as the key habitat variables influencing population dynamics. Yet habitat quality may also play an important role in influencing the regional persistence of spatially structured populations as the value or density of resources ...

Modern approaches to the design of memory and cognitive function stimulants based on AMPA receptor ligands

NASA Astrophysics Data System (ADS)

Grigoriev, V. V.; Proshin, A. N.; Kinzirsky, A. S.; Bachurin, Sergey O.

2009-05-01

Data on the structure and properties of compounds acting on AMPA receptors, the key subtype of ionotropic glutamate receptors of the mammalian central nervous system, are analyzed. Data on the role of these receptors in provision of memory and cognitive function formation and impairment processes are presented. The attention is focused on the modern views on the mechanisms of AMPA receptor desensitization and deactivation and action of substances affecting these processes. The structures of key positive modulators of AMPA receptors are given. The problems of application of these substances as therapeutic means for preventing and treating neurodegenerative and psychoneurological diseases are discussed. Bibliography — 121 references.

Evaluation of a novel mentor program to improve surgical care for US hospitals.

PubMed

Berian, Julia R; Thomas, Juliana M; Minami, Christina A; Farrell, Paula R; O'Leary, Kevin J; Williams, Mark V; Prachand, Vivek N; Halverson, Amy L; Bilimoria, Karl Y; Johnson, Julie K

2017-04-01

To evaluate a novel mentor program for 27 US surgeons, charged with improving quality at their respective hospitals, having been paired 1:1 with 27 surgeon mentors through a state-wide quality improvement (QI) initiative. Mixed-methods utilizing quantitative surveys and in-depth semi-structured interviews. The Illinois Surgical Quality Improvement Collaborative (ISQIC) utilized a novel Mentor Program to guide surgeons new to QI. All mentor-mentee pairs received the survey (n = 27). Purposive sampling identified a subset of mentors (n = 8) and mentees (n = 4) for in-depth semi-structured interviews. Surgeons with expertise in QI mentored surgeons new to QI. (i) Quantitative: self-reported satisfaction with the mentor program; (ii) Qualitative: key themes suggesting actions and strategies to facilitate mentorship in QI. Mentees expressed satisfaction with the mentor program (n = 24, 88.9%) and agreed that mentorship is vital to ISQIC (n = 24, 88.9%). Analysis of interview data revealed four key themes: (i) nuances of data management, (ii) culture of quality and safety, (iii) mentor-mentee relationship and (iv) logistics. Strategies from these key themes include: utilize raw data for in-depth QI understanding, facilitate presentations to build QI support, identify opportunities for in-person meetings and establish scheduled conference calls. The mentor's role required sharing experiences and acting as a resource. The mentee's role required actively bringing questions and identifying barriers. Mentorship plays a vital role in advancing surgeon knowledge and engagement with QI in ISQIC. Key themes in mentorship reflect strategies to best facilitate mentorship, which may serve as a guide to other collaboratives. © The Author 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Dynamic features of carboxy cytoglobin distal mutants investigated by molecular dynamics simulations.

PubMed

Zhao, Cong; Du, Weihong

2016-04-01

Cytoglobin (Cgb) is a member of hemoprotein family with roles in NO metabolism, fibrosis, and tumourigenesis. Similar to other hemoproteins, Cgb structure and functions are markedly influenced by distal key residues. The sixth ligand His(81) (E7) is crucial to exogenous ligand binding, heme pocket conformation, and physiological roles of this protein. However, the effects of other key residues on heme pocket and protein biological functions are not well known. In this work, a molecular dynamics (MD) simulation study of two single mutants in CO-ligated Cgb (L46FCgbCO and L46VCgbCO) and two double mutants (L46FH81QCgbCO and L46VH81QCgbCO) was conducted to explore the effects of the key distal residues Leu(46)(B10) and His(81)(E7) on Cgb structure and functions. Results indicated that the distal mutation of B10 and E7 affected CgbCO dynamic properties on loop region fluctuation, internal cavity rearrangement, and heme motion. The distal conformation change was reflected by the distal key residues Gln(62) (CD3) and Arg(84)(E10). The hydrogen bond between heme propionates with CD3 or E10 residues were evidently influenced by B10/E7 mutation. Furthermore, heme pocket rearrangement was also observed based on the distal pocket volume and occurrence rate of inner cavities. The mutual effects of B10 and E7 residues on protein conformational rearrangement and other dynamic features were expressed in current MD studies of CgbCO and its distal mutants, suggesting their crucial role in heme pocket stabilization, ligand binding, and Cgb biological functions. The mutation of distal B10 and E7 residues affects the dynamic features of carboxy cytoglobin.

Role of internal demagnetizing field for the dynamics of a surface-modulated magnonic crystal

NASA Astrophysics Data System (ADS)

Langer, M.; Röder, F.; Gallardo, R. A.; Schneider, T.; Stienen, S.; Gatel, C.; Hübner, R.; Bischoff, L.; Lenz, K.; Lindner, J.; Landeros, P.; Fassbender, J.

2017-05-01

This work aims to demonstrate and understand the key role of local demagnetizing fields in hybrid structures consisting of a continuous thin film with a stripe modulation on top. To understand the complex spin dynamics of these structures, the magnonic crystal was reconstructed in two different ways—performing micromagnetic simulations based on the structural shape as well as based on the internal demagnetizing field, which both are mapped on the nanoscale using electron holography. The simulations yield the frequency-field dependence as well as the angular dependence revealing the governing role of the internal field landscape around the backward-volume geometry. Simple rules for the propagation vector and the mode localization are formulated in order to explain the calculated mode profiles. Treating internal demagnetizing fields equivalent to anisotropies, the complex angle-dependent spin-wave behavior is described for an in-plane rotation of the external field.

Inter-organizational design: exploring the relationship between formal architecture and ICT investments

NASA Astrophysics Data System (ADS)

Iubatti, Daniela; Masciarelli, Francesca; Simboli, Alberto

This chapter aims to explore how the information-processing capabilities that emerge from a network structure affect the diffusion of innovation in a multidivisional organization. In particular, this study analyzes the role of firm investments in ICT to facilitate communication and knowledge diffusion. Using a qualitative approach, we investigate the behavior of an Italian multinational firm, Engineering S.p.A., analyzing our data using a content analysis procedure. Our results show the limited role of ICT in favoring knowledge exchange both inside and outside the firm's divisions: traditional communication patterns are generally preferred over the use of technologies for information sharing. Additionally, we find that key individuals who play a central role in the firm's communication network are unable to use ICTs for knowledge transfer. We conclude that this is the result of a strategic decision to keep top management practically unchanged since the firm was established. Therefore, key individuals act as filters to knowledge flows. Knowledge, in particular tacit knowledge, is transferred from key individuals to other actors through face-to-face contacts, thereby creating a diseconomy for the organization.

The role of religious leaders in health promotion for older Mexicans with diabetes.

PubMed

Rivera-Hernandez, Maricruz

2015-02-01

Clergy in the Mexico play a major role in addressing the health care needs of their congregants. With qualitative semi-structured key-informant interviews, this study explored the views of ten male Mexican religious leaders (mostly Catholic) about their understanding of their role in diabetes health promotion. The major themes from the qualitative interviews emphasized the importance of open communication between church leaders and their parishioners, the role of the church in diabetes programs, and the unique position of religious institutions as a link between physical and spiritual aspects of health. Implications for diabetes interventions are discussed.

Translations on Eastern Europe, Economic and Industrial Affairs, Number 1659

DTIC Science & Technology

1977-08-09

attainments in agriculture, forestry, and the food industry. 1?. Key ¥o« de and Document Analysis. 17o. Descriptors x International Affairs Albania... Structure Uneven Developments in Trade Balances Chapter III. Some Forms and Methods of Economic Relations Some Aspects of Role of Foreign Trade...to the extent that a modern economic structure , in keeping with the scientific-technological revolution, is being developed according to plan in

The National Security Policy Process: The National Security Council and Interagency System

DTIC Science & Technology

2008-11-24

Service Officer who has served as the State Department’s Deputy Executive Secretary, and also was U.S. Ambassador to the State of Qatar from 1998...creation under President Truman. It describes the current NSC organizational structure and processes, and defines the roles of the key departments and...of doing business. Finally, the paper comments upon how the interagency process is incorporating new organizational structures associated with

Strategic disruption of nuclear pores structure, integrity and barrier for nuclear apoptosis.

PubMed

Shahin, Victor

2017-08-01

Apoptosis is a programmed cell death playing key roles in physiology and pathophysiology of multi cellular organisms. Its nuclear manifestation requires transmission of the death signals across the nuclear pore complexes (NPCs). In strategic sequential steps apoptotic factors disrupt NPCs structure, integrity and barrier ultimately leading to nuclear breakdown. The present review reflects on these steps. Copyright © 2017 Elsevier Ltd. All rights reserved.

Degrees of Isolation: The Impact of Climate Change on the Dispersal and Population Genetic Structure of Two Antarctic Fish Species

NASA Astrophysics Data System (ADS)

Young, E. F.; Belchier, M.; Meredith, M. P.; Tysklind, N.; Carvalho, G. R.

2016-02-01

Understanding the key drivers of larval dispersal and population connectivity in the marine environment is essential for estimating the potential impacts of climate change on the genetic structure and resilience of populations. Small, isolated and fragmented communities will differ fundamentally in their response and resilience to environmental stress, compared with species that are broadly distributed, abundant, and with a frequent exchange of members. Using a `seascape genetics' approach, combining oceanographic modelling and genetic analyses, we have elucidated the fundamental roles of oceanographic transport and planktonic duration on the connectivity and population genetic structure of two Antarctic fish species with contrasting early life histories, Champsocephalus gunnari and Notothenia rossii. Here, we extend these analyses to consider the impact of rising sea temperatures due to climate change on planktonic dispersal and population connectivity. Using a theoretical approach, the effect of increased water temperatures on mortality rates and species-specific egg and larval phase durations has been incorporated into the models, and the relative impact of these climate-related influences on connectivity and population genetic structure has been investigated. Here we present the key findings of our research and consider the roles of early life history and oceanography in the response of fragmented fish populations to climate change.

On the design and structural analysis of jet engine fan blade structures

NASA Astrophysics Data System (ADS)

Amoo, Leye M.

2013-07-01

Progress in the design and structural analysis of commercial jet engine fan blades is reviewed and presented. This article is motivated by the key role fan blades play in the performance of advanced gas turbine jet engines. The fundamentals of the associated physics are emphasized. Recent developments and advancements have led to an increase and improvement in fan blade structural durability, stability and reliability. This article is intended as a high level review of the fan blade environment and current state of structural design to aid further research in developing new and innovative fan blade technologies.

4-Hydroxyphenylpyruvate Dioxygenase Catalysis

PubMed Central

Raspail, Corinne; Graindorge, Matthieu; Moreau, Yohann; Crouzy, Serge; Lefèbvre, Bertrand; Robin, Adeline Y.; Dumas, Renaud; Matringe, Michel

2011-01-01

4-Hydroxyphenylpyruvate dioxygenase (HPPD) catalyzes the conversion of 4-hydroxyphenylpyruvate (HPP) into homogentisate. HPPD is the molecular target of very effective synthetic herbicides. HPPD inhibitors may also be useful in treating life-threatening tyrosinemia type I and are currently in trials for treatment of Parkinson disease. The reaction mechanism of this key enzyme in both plants and animals has not yet been fully elucidated. In this study, using site-directed mutagenesis supported by quantum mechanical/molecular mechanical theoretical calculations, we investigated the role of catalytic residues potentially interacting with the substrate/intermediates. These results highlight the following: (i) the central role of Gln-272, Gln-286, and Gln-358 in HPP binding and the first nucleophilic attack; (ii) the important movement of the aromatic ring of HPP during the reaction, and (iii) the key role played by Asn-261 and Ser-246 in C1 hydroxylation and the final ortho-rearrangement steps (numbering according to the Arabidopsis HPPD crystal structure 1SQD). Furthermore, this study reveals that the last step of the catalytic reaction, the 1,2 shift of the acetate side chain, which was believed to be unique to the HPPD activity, is also catalyzed by a structurally unrelated enzyme. PMID:21613226

The role of the human pulvinar in visual attention and action: evidence from temporal-order judgment, saccade decision, and antisaccade tasks.

PubMed

Arend, Isabel; Machado, Liana; Ward, Robert; McGrath, Michelle; Ro, Tony; Rafal, Robert D

2008-01-01

The pulvinar nucleus of the thalamus has been considered as a key structure for visual attention functions (Grieve, K.L. et al. (2000). Trends Neurosci., 23: 35-39; Shipp, S. (2003). Philos. Trans. R. Soc. Lond. B Biol. Sci., 358(1438): 1605-1624). During the past several years, we have studied the role of the human pulvinar in visual attention and oculomotor behaviour by testing a small group of patients with unilateral pulvinar lesions. Here we summarize some of these findings, and present new evidence for the role of this structure in both eye movements and visual attention through two versions of a temporal-order judgment task and an antisaccade task. Pulvinar damage induces an ipsilesional bias in perceptual temporal-order judgments and in saccadic decision, and also increases the latency of antisaccades away from contralesional targets. The demonstration that pulvinar damage affects both attention and oculomotor behaviour highlights the role of this structure in the integration of visual and oculomotor signals and, more generally, its role in flexibly linking visual stimuli with context-specific motor responses.

Shifts in bacterial community structure during succession in a glacier foreland of the High Arctic.

PubMed

Kim, Mincheol; Jung, Ji Young; Laffly, Dominique; Kwon, Hye Young; Lee, Yoo Kyung

2017-01-01

Primary succession after glacier retreat has been widely studied in plant communities, but bacterial succession is still poorly understood. In particular, few studies of microbial succession have been performed in the Arctic. We investigated the shifts in bacterial community structure and soil physicochemical properties along a successional gradient in a 100-year glacier foreland of the High Arctic. Multivariate analyses revealed that time after glacier retreat played a key role in associated bacterial community structure during succession. However, environmental filtering (i.e. pH and soil temperature) also accounted for a different, but substantial, proportion of the bacterial community structure. Using the functional trait-based approach, we found that average rRNA operon (rrn) copy number of bacterial communities is high in earlier successional stages and decreased over time. This suggests that soil bacterial taxa with higher rrn copy number have a selective advantage in early successional stages due to their ability of rapidly responding to nutrient inputs in newly exposed soils after glacier retreat. Taken together, our results demonstrate that both deglaciation time and environmental filters play key roles in structuring bacterial communities and soil bacterial groups with different ecological strategies occur in different stages of succession in this glacier foreland. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Conformational control of cofactors in nature: The effect of methoxy group orientation on the electronic structure of ubisemiquinone

NASA Astrophysics Data System (ADS)

De Almeida, Wagner B.; O'Malley, Patrick J.

2018-03-01

Ubiquinone is the key electron and proton transfer agent in biology. Its mechanism involves the formation of its intermediate one-electron reduced form, the ubisemiquinone radical. This is formed in a protein-bound form which permits the semiquinone to vary its electronic and redox properties. This can be achieved by hydrogen bonding acceptance by one or both oxygen atoms or as we now propose by restricted orientations for the methoxy groups of the headgroup. We show how the orientation of the two methoxy groups of the quinone headgroup affects the electronic structure of the semiquinone form and demonstrate a large dependence of the ubisemiquinone spin density distribution on the orientation each methoxy group takes with respect to the headgroup ring plane. This is shown to significantly modify associated hyperfine couplings which in turn needs to be accounted for in interpreting experimental values in vivo. The study uncovers the key potential role the methoxy group orientation can play in controlling the electronic structure and spin density of ubisemiquinone and provides an electronic-level insight into the variation in electron affinity and redox potential of ubiquinone as a function of the methoxy orientation. Taken together with the already known influence of cofactor conformation on heme and chlorophyll electronic structure, it reveals a more widespread role for cofactor conformational control of electronic structure and associated electron transfer in biology.

Laboratory information management system for membrane protein structure initiative--from gene to crystal.

PubMed

Troshin, Petr V; Morris, Chris; Prince, Stephen M; Papiz, Miroslav Z

2008-12-01

Membrane Protein Structure Initiative (MPSI) exploits laboratory competencies to work collaboratively and distribute work among the different sites. This is possible as protein structure determination requires a series of steps, starting with target selection, through cloning, expression, purification, crystallization and finally structure determination. Distributed sites create a unique set of challenges for integrating and passing on information on the progress of targets. This role is played by the Protein Information Management System (PIMS), which is a laboratory information management system (LIMS), serving as a hub for MPSI, allowing collaborative structural proteomics to be carried out in a distributed fashion. It holds key information on the progress of cloning, expression, purification and crystallization of proteins. PIMS is employed to track the status of protein targets and to manage constructs, primers, experiments, protocols, sample locations and their detailed histories: thus playing a key role in MPSI data exchange. It also serves as the centre of a federation of interoperable information resources such as local laboratory information systems and international archival resources, like PDB or NCBI. During the challenging task of PIMS integration, within the MPSI, we discovered a number of prerequisites for successful PIMS integration. In this article we share our experiences and provide invaluable insights into the process of LIMS adaptation. This information should be of interest to partners who are thinking about using LIMS as a data centre for their collaborative efforts.

Maintenance of a functional higher order chromatin structure: The role of the nuclear matrix in normal and disease states

PubMed Central

Linnemann, Amelia K.; Krawetz, Stephen A.

2010-01-01

Summary The ordered packaging of DNA within the nucleus of somatic cells reflects a dynamic supportive structure that facilitates stable transcription interrupted by intermittent cycles of extreme condensation. This dynamic mode of packing and unpacking chromatin is intimately linked to the ability of the genome to specifically complex with both histones and non-histone proteins. Understanding the underlying mechanism that governs the formation of higher order chromatin structures is a key to understanding how local architecture modulates transcription. In part, the formation of these structures appears to be regulated through genomic looping that is dynamically mediated by attachment to the nuclear scaffold/matrix at S/MARs, i.e., Scaffold/Matrix Attachment Regions. Although the mechanism guiding the formation and use of these higher-ordered structures remains unknown, S/MARs continue to reveal a multitude of roles in development and the pathogenesis of disease. PMID:20948980

Maintenance of a functional higher order chromatin structure: The role of the nuclear matrix in normal and disease states.

PubMed

Linnemann, Amelia K; Krawetz, Stephen A

2009-01-01

The ordered packaging of DNA within the nucleus of somatic cells reflects a dynamic supportive structure that facilitates stable transcription interrupted by intermittent cycles of extreme condensation. This dynamic mode of packing and unpacking chromatin is intimately linked to the ability of the genome to specifically complex with both histones and non-histone proteins. Understanding the underlying mechanism that governs the formation of higher order chromatin structures is a key to understanding how local architecture modulates transcription. In part, the formation of these structures appears to be regulated through genomic looping that is dynamically mediated by attachment to the nuclear scaffold/matrix at S/MARs, i.e., Scaffold/Matrix Attachment Regions. Although the mechanism guiding the formation and use of these higher-ordered structures remains unknown, S/MARs continue to reveal a multitude of roles in development and the pathogenesis of disease.

[alpha]-Oxocarboxylic Acids

ERIC Educational Resources Information Center

Kerber, Robert C.; Fernando, Marian S.

2010-01-01

Several [alpha]-oxocarboxylic acids play key roles in metabolism in plants and animals. However, there are inconsistencies between the structures as commonly portrayed and the reported acid ionization constants, which result because the acids are predominantly hydrated in aqueous solution; that is, the predominant form is RC(OH)[subscript 2]COOH…

Loss of tight junction barrier function and its role in cancer metastasis.

PubMed

Martin, Tracey A; Jiang, Wen G

2009-04-01

As the most apical structure between epithelial and endothelial cells, tight junctions (TJ) are well known as functioning as a control for the paracellular diffusion of ions and certain molecules. It has however, become increasingly apparent that the TJ has a vital role in maintaining cell to cell integrity and that the loss of cohesion of the structure can lead to invasion and thus metastasis of cancer cells. This article will present data showing how modulation of expression of TJ molecules results in key changes in TJ barrier function leading to the successful metastasis of a number of different cancer types.

FIBER OPTICS: Role of point defects in the photosensitivity of hydrogen-loaded phosphosilicate glass

NASA Astrophysics Data System (ADS)

Larionov, Yu V.

2010-08-01

It is shown that point defect modifications in hydrogen-loaded phosphosilicate glass (PSG) do not play a central role in determining its photosensitivity. Photochemical reactions that involve a two-step point defect modification and pre-exposure effect are incapable of accounting for photoinduced refractive index changes. It seems likely that a key role in UV-induced refractive index modifications is played by structural changes in the PSG network. Experimental data are presented that demonstrate intricate network rearrangement dynamics during UV exposure of PSG.

S-nitrosylation of the thioredoxin-like domains of protein disulfide isomerase and its role in neurodegenerative conditions.

NASA Astrophysics Data System (ADS)

Conway, Myra; Harris, Matthew

2015-04-01

Correct protein folding and inhibition of protein aggregation is facilitated by a cellular ‘quality control system’ that engages a network of protein interactions including molecular chaperones and the ubiquitin proteasome system. Key chaperones involved in these regulatory mechanisms are the protein disulphide isomerases (PDI) and their homologues, predominantly expressed in the endoplasmic reticulum of most tissues. Redox changes that disrupt ER homeostasis can lead to modification of these enzymes or chaperones with the loss of their proposed neuroprotective role resulting in an increase in protein misfolding. Misfolded protein aggregates have been observed in several disease states and are considered to play a pivotal role in the pathogenesis of neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral sclerosis. This review will focus on the importance of the thioredoxin-like -CGHC- active site of PDI and how our understanding of this structural motif will play a key role in unravelling the pathogenic mechanisms that underpin these neurodegenerative conditions.

Study Partners Perform Essential Tasks in Dementia Research and Can Experience Burdens and Benefits in This Role

PubMed Central

Black, Betty S.; Taylor, Holly A.; Rabins, Peter V.; Karlawish, Jason

2016-01-01

Most studies that enroll individuals with dementia require a study partner for each participant. Study partners—usually family members—perform several key roles: accompanying the participant to visits, providing information about the participant, and assisting with procedures such as taking medication. Little is known, however, about their experiences when performing these roles. Dementia researchers and institutional review boards (IRBs) need to know these experiences because the study partner role is one key factor in a study’s success. This prospective qualitative study, using up to three semi-structured interviews with 62 study partners involved in a range of dementia studies, documented their subjective experiences. Content analysis demonstrates that study partners perform a range of tasks—often within the context of being a caregiver—that enable cognitively impaired individuals to participate in dementia research. These tasks present study partners with unique burdens and benefits, some of which dementia researchers and IRBs can address. PMID:27179001

Correlation between the hierarchical structures and nanomechanical properties of amyloid fibrils.

PubMed

Lee, Gyudo; Lee, Wonseok; Baik, Seunghyun; Kim, Yong Ho; Eom, Kilho; Kwon, Taeyun

2018-04-12

Amyloid fibrils have recently been highlighted due to their excellent mechanical properties, which not only play a role in their biological functions but also imply their applications in biomimetic material design. Despite recent efforts to unveil how the excellent mechanical properties of amyloid fibrils originate, it has remained elusive how the anisotropic nanomechanical properties of hierarchically structured amyloid fibrils are determined. Here, we characterize the anisotropic nanomechanical properties of hierarchically structured amyloid fibrils using atomic force microscopy (AFM) experiments and atomistic simulations. It is shown that the hierarchical structure of amyloid fibrils plays a crucial role in determining their radial elastic property but does not make any effect on their radial bending elastic property. This is attributed to the role of intermolecular force acting between the filaments (constituting the fibril) on the radial elastic modulus of amyloid fibrils. Our finding illustrates how the hierarchical structure of amyloid fibrils encodes their anisotropic nanomechanical properties. Our study provides key design principles of amyloid fibrils, which endow valuable insight into the underlying mechanisms of amyloid mechanics. © 2018 IOP Publishing Ltd.

Prefrontal cortical BDNF: A regulatory key in cocaine- and food-reinforced behaviors

PubMed Central

Pitts, Elizabeth G.; Taylor, Jane R.; Gourley, Shannon L.

2016-01-01

Brain-derived neurotrophic factor (BDNF) affects synaptic plasticity and neural structure and plays key roles in learning and memory processes. Recent evidence also points to important, yet complex, roles for BDNF in rodent models of cocaine abuse and addiction. Here we examine the role of prefrontal cortical (PFC) BDNF in reward-related decision making and behavioral sensitivity to, and responding for, cocaine. We focus on BDNF within the medial and orbital PFC, its regulation by cocaine during early postnatal development and in adulthood, and how BDNF in turn influences responding for drug reinforcement, including in reinstatement models. When relevant, we draw comparisons and contrasts with experiments using natural (food) reinforcers. We also summarize findings supporting, or refuting, the possibility that BDNF in the medial and orbital PFC regulate the development and maintenance of stimulus-response habits. Further investigation could assist in the development of novel treatment approaches for cocaine use disorders. PMID:26923993

Defining the molecular structure of teixobactin analogues and understanding their role in antibacterial activities.

PubMed

Parmar, Anish; Prior, Stephen H; Iyer, Abhishek; Vincent, Charlotte S; Van Lysebetten, Dorien; Breukink, Eefjan; Madder, Annemieke; Taylor, Edward J; Singh, Ishwar

2017-02-07

The discovery of the highly potent antibiotic teixobactin, which kills the bacteria without any detectable resistance, has stimulated interest in its structure-activity relationship. However, a molecular structure-activity relationship has not been established so far for teixobactin. Moreover, the importance of the individual amino acids in terms of their l/d configuration and their contribution to the molecular structure and biological activity are still unknown. For the first time, we have defined the molecular structure of seven teixobactin analogues through the variation of the d/l configuration of its key residues, namely N-Me-d-Phe, d-Gln, d-allo-Ile and d-Thr. Furthermore, we have established the role of the individual d amino acids and correlated this with the molecular structure and biological activity. Through extensive NMR and structural calculations, including molecular dynamics simulations, we have revealed the residues for maintaining a reasonably unstructured teixobactin which is imperative for biological activity.

Binding and Inactivation Mechanism of a Humanized Fatty Acid Amide Hydrolase by [alpha]-Ketoheterocycle Inhibitors Revealed from Cocrystal Structures

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

Mileni, Mauro; Garfunkle, Joie; DeMartino, Jessica K.

The cocrystal X-ray structures of two isomeric {alpha}-ketooxazole inhibitors (1 (OL-135) and 2) bound to fatty acid amide hydrolase (FAAH), a key enzymatic regulator of endocannabinoid signaling, are disclosed. The active site catalytic Ser241 is covalently bound to the inhibitors electrophilic carbonyl groups, providing the first structures of FAAH bound to an inhibitor as a deprotonated hemiketal mimicking the enzymatic tetrahedral intermediate. The work also offers a detailed view of the oxyanion hole and an exceptional 'in-action' depiction of the unusual Ser-Ser-Lys catalytic triad. These structures capture the first picture of inhibitors that span the active site into the cytosolicmore » port providing new insights that help to explain FAAH's interaction with substrate leaving groups and their role in modulating inhibitor potency and selectivity. The role for the activating central heterocycle is clearly defined and distinguished from that observed in prior applications with serine proteases, reconciling the large electronic effect of attached substituents found unique to this class of inhibitors with FAAH. Additional striking active site flexibility is seen upon binding of the inhibitors, providing insights into the existence of a now well-defined membrane access channel with the disappearance of a spatially independent portion of the acyl chain-binding pocket. Finally, comparison of the structures of OL-135 (1) and its isomer 2 indicates that they bind identically to FAAH, albeit with reversed orientations of the central activating heterocycle, revealing that the terminal 2-pyridyl substituent and the acyl chain phenyl group provide key anchoring interactions and confirming the distinguishing role of the activating oxazole.« less

Focus groups to explore healthcare professionals' experiences of care coordination: towards a theoretical framework for the study of care coordination.

PubMed

Van Houdt, Sabine; Sermeus, Walter; Vanhaecht, Kris; De Lepeleire, Jan

2014-12-24

Strategies to improve care coordination between primary and hospital care do not always have the desired results. This is partly due to incomplete understanding of the key concepts of care coordination. An in-depth analysis of existing theoretical frameworks for the study of care coordination identified 14 interrelated key concepts. In another study, these 14 key concepts were further explored in patients' experiences. Additionally, "patient characteristics" was identified as a new key concept in patients' experiences and the previously identified key concept "quality of relationship" between healthcare professionals was extended to "quality of relationship" with the patient. Together, these 15 interrelated key concepts resulted in a new theoretical framework. The present study aimed at improving our understanding of the 15 previously identified key concepts and to explore potentially previous unidentified key concepts and the links between these by exploring how healthcare professionals experience care coordination. A qualitative design was used. Six focus groups were conducted including primary healthcare professionals involved in the care of patients who had breast cancer surgery at three hospitals in Belgium. Data were analyzed using constant comparative analysis. All 15 previously identified key concepts of care coordination were further explored in healthcare professionals' experiences. Links between these 15 concepts were identified, including 9 newly identified links. The concept "external factors" was linked with all 6 concepts relating to (inter)organizational mechanisms; "task characteristics", "structure", "knowledge and information technology", "administrative operational processes", "cultural factors" and "need for coordination". Five of these concepts related to 3 concepts of relational coordination; "roles", "quality of relationship" and "exchange of information". The concept of "task characteristics" was only linked with "roles" and "exchange of information". The concept "patient characteristics" related with the concepts "need for coordination" and "patient outcome". Outcome was influenced by "roles", "quality of relationship" and "exchange of information". External factors and the (inter)organizational mechanism should enhance "roles" and "quality of relationship" between healthcare professionals and with the patient as well as "exchange of information", and setting and sharing of common "goals" to improve care coordination and quality of care.

Role of Polyalanine Domains in -Sheet Formation in Spider Silk Block Copolymers

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

Rabotyagova, O.; Cebe, P; Kaplan, D

2010-01-01

Genetically engineered spider silk-like block copolymers were studied to determine the influence of polyalanine domain size on secondary structure. The role of polyalanine block distribution on {beta}-sheet formation was explored using FT-IR and WAXS. The number of polyalanine blocks had a direct effect on the formation of crystalline {beta}-sheets, reflected in the change in crystallinity index as the blocks of polyalanines increased. WAXS analysis confirmed the crystalline nature of the sample with the largest number of polyalanine blocks. This approach provides a platform for further exploration of the role of specific amino acid chemistries in regulating the assembly of {beta}-sheetmore » secondary structures, leading to options to regulate material properties through manipulation of this key component in spider silks.« less

Towards a Theory of Leadership Practice: A Distributed Perspective

ERIC Educational Resources Information Center

Spillane, James; Halverson, Richard; Diamond, John

2004-01-01

School-level conditions and school leadership, in particular, are key issues in efforts to change instruction. While new organizational structures and new leadership roles matter to instructional innovation, what seems most critical is how leadership practice is undertaken. Yet, the practice of school leadership has received limited attention in…

The Role of Local Leaders in Cultural Transformation and Development

ERIC Educational Resources Information Center

Carm, Ellen

2012-01-01

Through cross-disciplinary and participatory processes involving key stakeholders from the Zambian education sector, as well as from the traditional leadership structure, a localized HIV/AIDS-prevention strategy, Interactive School and Community Approach (ISACA), was developed and implemented throughout one province between 2002 and 2006. The…

Teachers' Perceptions of the Principal Role and Actions in Successful Professional Learning Communities

ERIC Educational Resources Information Center

Dilmar, Amy D.

2017-01-01

Despite millions of dollars spent on reform efforts, effective and sustainable improvement still eludes schools. The appropriate development of the professional learning community model, including five key dimensions, provides a structure for educational institutions to bring about sustainable improvements in student achievement. If principals do…

The Role of Psychosocial School Conditions in Adolescent Prosocial Behaviour

ERIC Educational Resources Information Center

Plenty, Stephanie; Östberg, Viveca; Modin, Bitte

2015-01-01

This study examined how psychosocial conditions at school are associated with prosocial behaviour, a key indicator of positive mental health. Participants were 3,652 Swedish Grade 9 students from the Health Behaviour in School-aged Children study. Structural equation modelling demonstrated that students who experience more manageable school…

Outstanding effects on antithrombin activity of modified TBA diastereomers containing an optically pure acyclic nucleotide analogue.

PubMed

Scuotto, M; Persico, M; Bucci, M; Vellecco, V; Borbone, N; Morelli, E; Oliviero, G; Novellino, E; Piccialli, G; Cirino, G; Varra, M; Fattorusso, C; Mayol, L

2014-07-28

Herein, we report optically pure modified acyclic nucleosides as ideal probes for aptamer modification. These new monomers offer unique advantages in exploring the role played in thrombin inhibition by a single residue modification at key positions of the TBA structure.

Current Genetic Discoveries and Education: "Strengths, Opportunities, and Limitations"

ERIC Educational Resources Information Center

Bates, Timothy C.

2008-01-01

This article notes that many key positive developments in education originated in research on the structure and genetics of abilities, providing primary evidence for ability in disadvantaged groups and playing a critical role in demonstrating the existence of developmental learning disorders and effective interventions. It is argued that new work…

The Heuristics of Statistical Argumentation: Scaffolding at the Postsecondary Level

ERIC Educational Resources Information Center

Pardue, Teneal Messer

2017-01-01

Language plays a key role in statistics and, by extension, in statistics education. Enculturating students into the practice of statistics requires preparing them to communicate results of data analysis. Statistical argumentation is one way of providing structure to facilitate discourse in the statistics classroom. In this study, a teaching…

Perceptual Learning Immediately Yields New Stable Motor Coordination

ERIC Educational Resources Information Center

Wilson, Andrew D.; Snapp-Childs, Winona; Bingham, Geoffrey P.

2010-01-01

Coordinated rhythmic movement is specifically structured in humans. Movement at 0[degrees] mean relative phase is maximally stable, 180[degrees] is less stable, and other coordinations can, but must, be learned. Variations in perceptual ability play a key role in determining the observed stabilities so we investigated whether stable movements can…

The Work/Family Challenge: A Key Career Development Issue.

ERIC Educational Resources Information Center

Kahnweiler, William M; Kahnweiler, Jennifer B.

1992-01-01

A few corporations are responding to the impact of family structural changes on workers' ability to balance their roles with flexible benefits and schedules and with training. Work/family issues are an integral part of career and life decision making and must be incorporated into the career development process. (SK)

RxnFinder: biochemical reaction search engines using molecular structures, molecular fragments and reaction similarity.

PubMed

Hu, Qian-Nan; Deng, Zhe; Hu, Huanan; Cao, Dong-Sheng; Liang, Yi-Zeng

2011-09-01

Biochemical reactions play a key role to help sustain life and allow cells to grow. RxnFinder was developed to search biochemical reactions from KEGG reaction database using three search criteria: molecular structures, molecular fragments and reaction similarity. RxnFinder is helpful to get reference reactions for biosynthesis and xenobiotics metabolism. RxnFinder is freely available via: http://sdd.whu.edu.cn/rxnfinder. qnhu@whu.edu.cn.

Unity in diversity: structural and functional insights into the ancient partnerships between plants and fungi.

PubMed

Field, Katie J; Pressel, Silvia

2018-04-26

Contents I. II. III. IV. V. VI. VII. VIII. References SUMMARY: Mycorrhizal symbiosis is an ancient and widespread mutualism between plants and fungi that facilitated plant terrestrialisation > 500 million years ago, with key roles in ecosystem functioning at multiple scales. Central to the symbiosis is the bidirectional exchange of plant-fixed carbon for fungal-acquired nutrients. Within this unifying role of mycorrhizas, considerable diversity in structure and function reflects the diversity of the partners involved. Early diverging plants form mutualisms not only with arbuscular mycorrhizal Glomeromycotina fungi, but also with poorly characterised Mucoromycotina, which may also colonise the roots of 'higher' plants as fine root endophytes. Functional diversity in these symbioses depends on both fungal and plant life histories and is influenced by the environment. Recent studies have highlighted the roles of lipids/fatty acids in plant-to-fungus carbon transport and potential contributions of Glomeromycotina fungi to plant nitrogen nutrition. Together with emerging appreciation of mycorrhizal networks as multi-species resource-sharing systems, these insights are broadening our views on mycorrhizas and their roles in nutrient cycling. It is crucial that the diverse array of biotic and abiotic factors that together shape the dynamics of carbon-for-nutrient exchange between plants and fungi are integrated, in addition to embracing the unfolding and potentially key role of Mucoromycotina fungi in these processes. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

The role of glia in late-life depression.

PubMed

Paradise, Matt Bennett; Naismith, Sharon Linda; Norrie, Louisa Margaret; Graeber, Manuel Benedikt; Hickie, Ian Bernard

2012-12-01

Late-life depression (LLD) has a complex and multifactoral etiology. There is growing interest in elucidating how glia, acting alone or as part of a glial-neuronal network, may contribute to the pathophysiology of depression. In this paper, we explore results from neuroimaging studies showing gray-matter volume loss in key frontal and subcortical structures implicated in LLD, and present the few histological studies that have examined neuronal and glial densities in these regions. Compared to results in younger people with depression, there appear to be age-dependent differences in neuronal pathology but the changes in glial pathology may be more subtle, perhaps reflecting a longer-term compensatory gliosis to earlier damage. We then consider the mechanisms by which both astrocytes and microglia may mediate and modulate neuronal dysfunction and possible degeneration in depression. These include a critical role in the response to peripheral inflammation and central microglial activation, as well as a key role in glutamate metabolism. Advances in our understanding of glia are highlighted, including the role of microglia as "electricians" of the brain and astrocytes as key communicating cells, an integral part of the tripartite synapse. Finally, implications for clinicians are discussed, including the consideration of glia as biomarkers for LLD and incorporation of glia into future therapeutic strategies.

Aspartate 102 in the Heme Domain of Soluble Guanylyl Cyclase Has a Key Role in NO Activation

PubMed Central

Baskaran, Padmamalini; Heckler, Erin J.; van den Akker, Focco; Beuve, Annie

2012-01-01

Nitric oxide (NO) is involved in the physiology and pathophysiology of the cardiovascular and neuronal systems via activation of soluble guanylyl cyclase (sGC), a heme-containing heterodimer. Recent structural studies have allowed a better understanding of the residues that dictate the affinity and binding of NO to the heme and the resulting breakage of the bond between the heme iron and histidine 105 (H105) of the β subunit of sGC. Still, it is unknown how the breakage of the iron–His bond translates into NO-dependent increased catalysis. Structural studies on homologous H-NOX domains in various states pointed to a role for movement of the H105 containing αF helix. Our modeling of the heme-binding domain highlighted conserved residues in the vicinity of H105 that could potentially regulate the extent to which the αF helix shifts and/or propagate the activation signal once the covalent bond with H105 has been broken. These include a direct interaction of αF helix residue D102 with the backbone nitrogen of F120. Mutational analysis of this region points to an essential role of the interactions in the vicinity of H105 for heme stability and identifies aspartate 102 (D102) as having a key role in NO activation following breakage of the iron–His bond. PMID:21491881

Ion-Neutral Coupling in Solar Prominence

NASA Technical Reports Server (NTRS)

Gilbert, H.; DeVore, C. R.; Karpen, J.; Kucera, T.; Antiochos, S.; Kawashima, R.

2011-01-01

Coupling between ions and neutrals in magnetized plasmas is fundamentally important to many aspects of heliophysics, including our ionosphere, the solar chromosphere, the solar wind interaction with planetary atmospheres, and the interface between the heliosphere and the interstellar medium. Ion-neutral coupling also plays a major role in the physics of solar prominences. By combining theory, modeling, and observations we are working toward a better understanding of the structure and dynamics of partially ionized prominence plasma. Two key questions are addressed in the present work: 1) what physical mechanism(s) sets the cross-field scale of prominence threads? 2) Are ion-neutral interactions responsible for the vertical flows and structure in prominences? We present initial results from a study investigating what role ion-neutral interactions play in prominence dynamics and structure. This research was supported by NASA.

Three key residues form a critical contact network in a protein folding transition state

NASA Astrophysics Data System (ADS)

Vendruscolo, Michele; Paci, Emanuele; Dobson, Christopher M.; Karplus, Martin

2001-02-01

Determining how a protein folds is a central problem in structural biology. The rate of folding of many proteins is determined by the transition state, so that a knowledge of its structure is essential for understanding the protein folding reaction. Here we use mutation measurements-which determine the role of individual residues in stabilizing the transition state-as restraints in a Monte Carlo sampling procedure to determine the ensemble of structures that make up the transition state. We apply this approach to the experimental data for the 98-residue protein acylphosphatase, and obtain a transition-state ensemble with the native-state topology and an average root-mean-square deviation of 6Å from the native structure. Although about 20 residues with small positional fluctuations form the structural core of this transition state, the native-like contact network of only three of these residues is sufficient to determine the overall fold of the protein. This result reveals how a nucleation mechanism involving a small number of key residues can lead to folding of a polypeptide chain to its unique native-state structure.

[Insulin-like growth factor-1 (IGF-1) - structure and the role in the human body].

PubMed

Filus, Alicja; Zdrojewicz, Zygmunt

2015-01-01

In the recent years, managed to broadly explore the structure and role of insulin-like growth factors type 1 and 2 (IGF1 I 2). They belong to the structure of polypeptide hormones homologous to proinsulin. They are characterized by a wide range of activities. IGF-1 is a key mediator of most tissue effects of growth hormone (GH). In addition to effects on growth processes of the body, is also an important factor for cell homeostasis, is subject to both endocrine and tissue-specific auto- and paracrine regulation. In this paper, the current, general knowledge on the structure, function and mechanism of biological effects of IGF-1 in the human body was presented. Attention was also drawn to the directions of use of IGf-1 in the treatment of other diseases than the diseases of the hypothalamic-pituitary and growth disorders in children. © Polish Society for Pediatric Endocrinology and Diabetology.

The diverse functions of the hepatitis B core/capsid protein (HBc) in the viral life cycle: Implications for the development of HBc-targeting antivirals.

PubMed

Diab, Ahmed; Foca, Adrien; Zoulim, Fabien; Durantel, David; Andrisani, Ourania

2018-01-01

Virally encoded proteins have evolved to perform multiple functions, and the core protein (HBc) of the hepatitis B virus (HBV) is a perfect example. While HBc is the structural component of the viral nucleocapsid, additional novel functions for the nucleus-localized HBc have recently been described. These results extend for HBc, beyond its structural role, a regulatory function in the viral life cycle and potentially a role in pathogenesis. In this article, we review the diverse roles of HBc in HBV replication and pathogenesis, emphasizing how the unique structure of this protein is key to its various functions. We focus in particular on recent advances in understanding the significance of HBc phosphorylations, its interaction with host proteins and the role of HBc in regulating the transcription of host genes. We also briefly allude to the emerging niche for new direct-acting antivirals targeting HBc, known as Core (protein) Allosteric Modulators (CAMs). Copyright © 2017 Elsevier B.V. All rights reserved.

Structural and functional characterization of the Mycobacterium tuberculosis uridine monophosphate kinase: insights into the allosteric regulation.

PubMed

Labesse, Gilles; Benkali, Khaled; Salard-Arnaud, Isabelle; Gilles, Anne-Marie; Munier-Lehmann, Hélène

2011-04-01

Nucleoside Monophosphate Kinases (NMPKs) family are key enzymes in nucleotide metabolism. Bacterial UMPKs depart from the main superfamily of NMPKs. Having no eukaryotic counterparts they represent attractive therapeutic targets. They are regulated by GTP and UTP, while showing different mechanisms in Gram(+), Gram(-) and archaeal bacteria. In this work, we have characterized the mycobacterial UMPK (UMPKmt) combining enzymatic and structural investigations with site-directed mutagenesis. UMPKmt exhibits cooperativity toward ATP and an allosteric regulation by GTP and UTP. The crystal structure of the complex of UMPKmt with GTP solved at 2.5 Å, was merely identical to the modelled apo-form, in agreement with SAXS experiments. Only a small stretch of residues was affected upon nucleotide binding, pointing out the role of macromolecular dynamics rather than major structural changes in the allosteric regulation of bacterial UMPKs. We further probe allosteric regulation by site-directed mutagenesis. In particular, a key residue involved in the allosteric regulation of this enzyme was identified.

The Potential Role Played by the Fullerene-Like Structures of Interstellar Carbon Dust in the Formation of Molecular Hydrogen in Space

NASA Astrophysics Data System (ADS)

Cataldo, Franco; Iglesias-Groth, Susana

After a general introduction to the problem of formation of molecular hydrogen from atomic hydrogen in the interstellar medium and in the dense molecular clouds in particular, and after the explanation of the key role played by the surfaces on this process, it is proposed that the most suitable carbon surface for the formation of molecular hydrogen (from the radiative association process of atomic hydrogen) can be represented by carbon black rather than by graphite. Furthermore, it is proposed that the fullerene-like structures present in the carbon black graphene sheets are the reaction sites where molecular hydrogen may be formed.

Structural Studies of Cinnamoyl-CoA Reductase and Cinnamyl-Alcohol Dehydrogenase, Key Enzymes of Monolignol Biosynthesis[C][W

PubMed Central

Pan, Haiyun; Zhou, Rui; Louie, Gordon V.; Mühlemann, Joëlle K.; Bomati, Erin K.; Bowman, Marianne E.; Dudareva, Natalia; Dixon, Richard A.; Noel, Joseph P.; Wang, Xiaoqiang

2014-01-01

The enzymes cinnamoyl-CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD) catalyze the two key reduction reactions in the conversion of cinnamic acid derivatives into monolignol building blocks for lignin polymers in plant cell walls. Here, we describe detailed functional and structural analyses of CCRs from Medicago truncatula and Petunia hybrida and of an atypical CAD (CAD2) from M. truncatula. These enzymes are closely related members of the short-chain dehydrogenase/reductase (SDR) superfamily. Our structural studies support a reaction mechanism involving a canonical SDR catalytic triad in both CCR and CAD2 and an important role for an auxiliary cysteine unique to CCR. Site-directed mutants of CAD2 (Phe226Ala and Tyr136Phe) that enlarge the phenolic binding site result in a 4- to 10-fold increase in activity with sinapaldehyde, which in comparison to the smaller coumaraldehyde and coniferaldehyde substrates is disfavored by wild-type CAD2. This finding demonstrates the potential exploitation of rationally engineered forms of CCR and CAD2 for the targeted modification of monolignol composition in transgenic plants. Thermal denaturation measurements and structural comparisons of various liganded and unliganded forms of CCR and CAD2 highlight substantial conformational flexibility of these SDR enzymes, which plays an important role in the establishment of catalytically productive complexes of the enzymes with their NADPH and phenolic substrates. PMID:25217505

Estrogen Receptor Folding Modulates cSrc Kinase SH2 Interaction via a Helical Binding Mode.

PubMed

Nieto, Lidia; Tharun, Inga M; Balk, Mark; Wienk, Hans; Boelens, Rolf; Ottmann, Christian; Milroy, Lech-Gustav; Brunsveld, Luc

2015-11-20

The estrogen receptors (ERs) feature, next to their transcriptional role, important nongenomic signaling actions, with emerging clinical relevance. The Src Homology 2 (SH2) domain mediated interaction between cSrc kinase and ER plays a key role in this; however the molecular determinants of this interaction have not been elucidated. Here, we used phosphorylated ER peptide and semisynthetic protein constructs in a combined biochemical and structural study to, for the first time, provide a quantitative and structural characterization of the cSrc SH2-ER interaction. Fluorescence polarization experiments delineated the SH2 binding motif in the ER sequence. Chemical shift perturbation analysis by nuclear magnetic resonance (NMR) together with molecular dynamics (MD) simulations allowed us to put forward a 3D model of the ER-SH2 interaction. The structural basis of this protein-protein interaction has been compared with that of the high affinity SH2 binding sequence GpYEEI. The ER features a different binding mode from that of the "two-pronged plug two-hole socket" model in the so-called specificity determining region. This alternative binding mode is modulated via the folding of ER helix 12, a structural element directly C-terminal of the key phosphorylated tyrosine. The present findings provide novel molecular entries for understanding nongenomic ER signaling and targeting the corresponding disease states.

Key vortical structure causing laminar-turbulent transition in a boundary layer disturbed by a short-duration jet

NASA Astrophysics Data System (ADS)

Yoshikawa, Joe; Nishio, Yu; Izawa, Seiichiro; Fukunishi, Yu

2018-01-01

Numerical simulations are carried out to discover the flow structure that plays an important role in the laminar-turbulent transition process of a boundary layer on a flat plate. The boundary layer is destabilized by ejecting a short-duration jet from a hole in the surface. When the jet velocity is set to 20% of the uniform-flow velocity, a laminar-turbulent transition takes place, whereas in the 18% case, the disturbances created by the jet decay downstream. It is found that in both cases, hairpin vortices are generated; however, these first-generation hairpins do not directly cause the transition. Only in the 20% case does a new hairpin vortex of a different shape with wider distance between the legs appear. The new hairpin grows with time and evokes the generation of vortical structures one after another around it, turning the flow turbulent. It is found that the difference between the two cases is whether or not one of the first-generation hairpin vortices gets connected with the nearby longitudinal vortices. Only when the connection is successful is the new hairpin vortex with wider distance between the legs created. For each of several cases tested with changing jet-ejecting conditions, no difference is found in the importance of the role of the hairpin structure. Therefore, we conclude that the hairpin vortex with widespread legs is a key structure in the transition to turbulence.

A computational analysis of the three isoforms of glutamate dehydrogenase reveals structural features of the isoform EC 1.4.1.4 supporting a key role in ammonium assimilation by plants

PubMed Central

Jaspard, Emmanuel

2006-01-01

Background There are three isoforms of glutamate dehydrogenase. The isoform EC 1.4.1.4 (GDH4) catalyses glutamate synthesis from 2-oxoglutarate and ammonium, using NAD(P)H. Ammonium assimilation is critical for plant growth. Although GDH4 from animals and prokaryotes are well characterized, there are few data concerning plant GDH4, even from those whose genomes are well annotated. Results A large set of the three GDH isoforms was built resulting in 116 non-redundant full polypeptide sequences. A computational analysis was made to gain more information concerning the structure – function relationship of GDH4 from plants (Eukaryota, Viridiplantae). The tested plant GDH4 sequences were the two ones known to date, those of Chlorella sorokiniana. This analysis revealed several structural features specific of plant GDH4: (i) the lack of a structure called "antenna"; (ii) the NAD(P)-binding motif GAGNVA; and (iii) a second putative coenzyme-binding motif GVLTGKG together with four residues involved in the binding of the reduced form of NADP. Conclusion A number of structural features specific of plant GDH4 have been found. The results reinforce the probable key role of GDH4 in ammonium assimilation by plants. Reviewers This article was reviewed by Tina Bakolitsa (nominated by Eugene Koonin), Martin Jambon (nominated by Laura Landweber), Sandor Pangor and Franck Eisenhaber. PMID:17173671

Androgen receptor: structure, role in prostate cancer and drug discovery

PubMed Central

Tan, MH Eileen; Li, Jun; Xu, H Eric; Melcher, Karsten; Yong, Eu-leong

2015-01-01

Androgens and androgen receptors (AR) play a pivotal role in expression of the male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS) and prostate cancer, are associated with alterations in AR functions. Indeed, androgen blockade by drugs that prevent the production of androgens and/or block the action of the AR inhibits prostate cancer growth. However, resistance to these drugs often occurs after 2–3 years as the patients develop castration-resistant prostate cancer (CRPC). In CRPC, a functional AR remains a key regulator. Early studies focused on the functional domains of the AR and its crucial role in the pathology. The elucidation of the structures of the AR DNA binding domain (DBD) and ligand binding domain (LBD) provides a new framework for understanding the functions of this receptor and leads to the development of rational drug design for the treatment of prostate cancer. An overview of androgen receptor structure and activity, its actions in prostate cancer, and how structural information and high-throughput screening have been or can be used for drug discovery are provided herein. PMID:24909511

Psychodrama: group psychotherapy through role playing.

PubMed

Kipper, D A

1992-10-01

The theory and the therapeutic procedure of classical psychodrama are described along with brief illustrations. Classical psychodrama and sociodrama stemmed from role theory, enactments, "tele," the reciprocity of choices, and the theory of spontaneity-robopathy and creativity. The discussion focuses on key concepts such as the therapeutic team, the structure of the session, transference and reality, countertransference, the here-and-now and the encounter, the group-as-a-whole, resistance and difficult clients, and affect and cognition. Also described are the neoclassical approaches of psychodrama, action methods, and clinical role playing, and the significance of the concept of behavioral simulation in group psychotherapy.

Building organizational capacity for a healthy work environment through role-based professional practice.

PubMed

Cornett, Patricia A; O'Rourke, Maria W

2009-01-01

The professional practice of registered nurses (RNs) and their professional role competence are key variables that have an impact on quality and patient safety. Organizations in which RNs practice must have the capacity to fully support the professional role of those RNs in exercising their legitimate power derived through nurse licensing laws and professional standards and ethics. The interplay of individual RN practice and organizational practice, and measurement thereof, are the essence of organizational capacity. Two models are discussed that tie together the attributes of healthy workplace environments and provide the structure to guide and sustain organizational capacity.

Neutrophil extracellular traps in immunity and disease.

PubMed

Papayannopoulos, Venizelos

2018-02-01

Neutrophils are innate immune phagocytes that have a central role in immune defence. Our understanding of the role of neutrophils in pathogen clearance, immune regulation and disease pathology has advanced dramatically in recent years. Web-like chromatin structures known as neutrophil extracellular traps (NETs) have been at the forefront of this renewed interest in neutrophil biology. The identification of molecules that modulate the release of NETs has helped to refine our view of the role of NETs in immune protection, inflammatory and autoimmune diseases and cancer. Here, I discuss the key findings and concepts that have thus far shaped the field of NET biology.

The challenges that employees who abuse substances experience when returning to work after completion of employee assistance programme (EAP).

PubMed

Soeker, Shaheed; Matimba, Tandokazi; Machingura, Last; Msimango, Henry; Moswaane, Bobo; Tom, Sinazo

2015-01-01

Employee assistance programs (EAPs) are responsible for helping employees cope with problems such as: mental distress, alcoholism and other drug dependencies, marital and financial difficulties--in short, the whole host of personal and family troubles endemic to the human condition. The study explored the challenges that employees who abuse substances experience when returning to work after the completion of an employee assistance program. The study used a qualitative exploratory descriptive research design. Three male participants and two key informants participated in the study. One semi structured interview was conducted with each one of the participants and one semi structured interview with the key informants. Four themes emerged: 1) Loss of one's worker role identity, 2) Negative influences of the community continues to effect the success of EAP, 3) EAP as a vehicle for change and, 4) Healthy occupations strengthen EAP. This study portrayed the following: how substance abuse effect the worker role of individuals employed in the open labor market, the challenges and facilitators experienced by employees who abuse substances when returning to their previous work roles and how occupation based interventions can be incorporated in EAP programs. Occupational therapists could use the health promotion approach, work simplification, energy conservation techniques and ergonomic analysis techniques.

A Native Threonine Coordinates Ordered Water to Tune Light-Oxygen-Voltage (LOV) Domain Photocycle Kinetics and Osmotic Stress Signaling in Trichoderma reesei ENVOY.

PubMed

Lokhandwala, Jameela; Silverman Y de la Vega, Rafael I; Hopkins, Hilary C; Britton, Collin W; Rodriguez-Iglesias, Aroa; Bogomolni, Roberto; Schmoll, Monika; Zoltowski, Brian D

2016-07-08

Light-oxygen-voltage (LOV) domain-containing proteins function as small light-activated modules capable of imparting blue light control of biological processes. Their small modular nature has made them model proteins for allosteric signal transduction and optogenetic devices. Despite intense research, key aspects of their signal transduction mechanisms and photochemistry remain poorly understood. In particular, ordered water has been identified as a possible key mediator of photocycle kinetics, despite the lack of ordered water in the LOV active site. Herein, we use recent crystal structures of a fungal LOV protein ENVOY to interrogate the role of Thr(101) in recruiting water to the flavin active site where it can function as an intrinsic base to accelerate photocycle kinetics. Kinetic and molecular dynamic simulations confirm a role in solvent recruitment to the active site and identify structural changes that correlate with solvent recruitment. In vivo analysis of T101I indicates a direct role of the Thr(101) position in mediating adaptation to osmotic stress, thereby verifying biological relevance of ordered water in LOV signaling. The combined studies identify position 101 as a mediator of both allostery and photocycle catalysis that can impact organism physiology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Ultimate Educational Aims, Overridingness, and Personal Well-Being

ERIC Educational Resources Information Center

Haji, Ishtiyaque; Cuypers, Stefaan E.

2011-01-01

Discussion regarding education's aims, especially its ultimate aims, is a key topic in the philosophy of education. These aims or values play a pivotal role in regulating and structuring moral and other types of normative education. We outline two plausible strategies to identify and justify education's ultimate aims. The first associates these…

77 FR 44674 - Solicitation for a Cooperative Agreement-National Institute of Corrections Inaugural Virtual...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-30

..., scheduling, promotion, production, and delivery of an NIC Virtual Conference entitled ``Handcuff Key to Door... conference through design, scheduling, promotion, and delivery; (2) In-studio and/or onsite production staff... in a project plan a detailed chart and description of a project management structure and team roles...

The Role of Future Time Perspective in Career Decision-Making

ERIC Educational Resources Information Center

Walker, Terrance L.; Tracey, Terence J. G.

2012-01-01

The present study of two hundred and seven university students examined the structural relation of future-orientation (both valence and instrumentality), career decision-making self-efficacy and career indecision (choice/commitment anxiety and lack of readiness) in a sample of 218 college students. Future time perspective was viewed as a key input…

SIPEX--Exploring the Antarctic Sea Ice Zone

ERIC Educational Resources Information Center

Zicus, Sandra; Dobson, Jane; Worby, Anthony

2008-01-01

Sea ice in the polar regions plays a key role in both regulating global climate and maintaining marine ecosystems. The international Sea Ice Physics and Ecosystem eXperiment (SIPEX) explored the sea ice zone around Antarctica in September and October 2007, investigating relationships between the physical sea ice environment and the structure of…

The Evolution of Frequency Distributions: Relating Regularization to Inductive Biases through Iterated Learning

ERIC Educational Resources Information Center

Reali, Florencia; Griffiths, Thomas L.

2009-01-01

The regularization of linguistic structures by learners has played a key role in arguments for strong innate constraints on language acquisition, and has important implications for language evolution. However, relating the inductive biases of learners to regularization behavior in laboratory tasks can be challenging without a formal model. In this…

Sierra Nevada grasslands: interactions between livestock grazing and ecosystem structure and function

Treesearch

Barbara H. Allen-Diaz

2004-01-01

Livestock grazing plays an integral role in the grass-dominated ecosystems of the Sierra Nevada. Grazing has been asserted to influence such key ecological characteristics as water quality, net primary productivity, nutrient cycling, plant and animal diversity, wildlife habitat availability, and oak regeneration (Belsky and others 1999, Kauffmann and Krueger 1984)....

Impaired Perception of Syllable Stress in Children with Dyslexia: A Longitudinal Study

ERIC Educational Resources Information Center

Goswami, Usha; Mead, Natasha; Fosker, Tim; Huss, Martina; Barnes, Lisa; Leong, Victoria

2013-01-01

Prosodic patterning is a key structural element of spoken language. However, the potential role of prosodic awareness in the phonological difficulties that characterise children with developmental dyslexia has been little studied. Here we report the first longitudinal study of sensitivity to syllable stress in children with dyslexia, enabling the…

Knowledge Creation and Human Capital for Development: The Role of Graduate Entrepreneurship

ERIC Educational Resources Information Center

Mitra, Jay; Abubakar, Y. A.; Sagagi, M.

2011-01-01

Purpose: Tackling structural and emergent problems in the labour market, valorising skilled human capital (HC) for opportunity creation, economic development and growth, are some of the key drivers for graduate entrepreneurship. This paper aims to examine developments in Africa, focusing on the significance of improving human capital through…

Report: EPA’s Information Systems and Data Are at Risk Due to Insufficient Training of Personnel With Significant Information Security Responsibilities

EPA Pesticide Factsheets

Report #14-P-0142, March 21, 2014. The EPA places its information systems and data at risk due to an organizational structure that has not specified required duties and responsibilities to ensure personnel are trained on key information security roles.

Adhesives with wood materials : bond formation and performance

Treesearch

Charles R. Frihart; Christopher G. Hunt

2010-01-01

Adhesive bonding of wood plays an increasing role in the forest products industry and is a key factor for efficiently utilizing our timber resource. The main use of adhesives is in the manufacture of building materials, including plywood, oriented strandboard, particleboard, fiberboard, structural composite lumber, doors, windows and frames, and factory-laminated wood...

An Interdisciplinary Approach to Understanding Readiness for University Partnerships

ERIC Educational Resources Information Center

Hancock, Lua

2014-01-01

Modern American higher education has blurred lines and roles of academic affairs, student affairs, and enrollment professionals. In a climate that pushes us to be assessment-driven, collaborative, outcomes-orientated, and student-centered, it is key that we have tools to clearly analyze our own campus culture and structures. Many of the areas that…

The Future of the National Technical Information Service: Issues and Options.

ERIC Educational Resources Information Center

McClure, Charles R.

In recent years there has been considerable debate about the appropriate role, management structure, and activities for the National Technical Information Service (NTIS). This background paper identifies key issues that require attention by Congress and by NTIS itself to increase the effectiveness of NTIS in the collection and dissemination of…

Common Molecules: Bringing Research and Teaching Together through an Online Collection.

ERIC Educational Resources Information Center

Sandvoss, Leah M.; Harwood, William S.; Korkmaz, Ali; Bollinger, John C.; Huffman, John C.; Huffman, John N.

2003-01-01

Describes the design of a Common Molecules collection that provides interactive tools for 3-D visualization of molecules. The organizational design provides not only structural information, but also historical and/or key information on the properties of the molecules in the collection. Describes student use of the collection and the role of…

Interactions between European Citizenship and Language Learning among Adolescent Europeans

ERIC Educational Resources Information Center

Hennebry, Mairin

2011-01-01

Recent enlargement of the European Union (EU) has created debate as to the suitability of current structures and policies for effectively engaging citizens and developing social cohesion. Education and specifically modern foreign language (MFL) teaching are argued by the literature to play a key role in equipping young people to interact and…

On time-dependent Hamiltonian realizations of planar and nonplanar systems

NASA Astrophysics Data System (ADS)

Esen, Oğul; Guha, Partha

2018-04-01

In this paper, we elucidate the key role played by the cosymplectic geometry in the theory of time dependent Hamiltonian systems in 2 D. We generalize the cosymplectic structures to time-dependent Nambu-Poisson Hamiltonian systems and corresponding Jacobi's last multiplier for 3 D systems. We illustrate our constructions with various examples.

Combinatorics of γ-structures.

PubMed

Han, Hillary S W; Li, Thomas J X; Reidys, Christian M

2014-08-01

In this article we study canonical γ-structures, a class of RNA pseudoknot structures that plays a key role in the context of polynomial time folding of RNA pseudoknot structures. A γ-structure is composed of specific building blocks that have topological genus less than or equal to γ, where composition means concatenation and nesting of such blocks. Our main result is the derivation of the generating function of γ-structures via symbolic enumeration using so called irreducible shadows. We furthermore recursively compute the generating polynomials of irreducible shadows of genus ≤ γ. The γ-structures are constructed via γ-matchings. For 1 ≤ γ ≤ 10, we compute Puiseux expansions at the unique, dominant singularities, allowing us to derive simple asymptotic formulas for the number of γ-structures.

Insights into substrate binding and catalysis in bacterial type I dehydroquinase.

PubMed

Maneiro, María; Peón, Antonio; Lence, Emilio; Otero, José M; Van Raaij, Mark J; Thompson, Paul; Hawkins, Alastair R; González-Bello, Concepción

2014-09-15

Structural, biochemical and computational studies to study substrate binding and the role of the conserved residues of the DHQ1 (type I dehydroquinase) enzyme active site are reported in the present paper. The crystal structure of DHQ1 from Salmonella typhi in complex with (2R)-2-methyl-3-dehydroquinic acid, a substrate analogue, was solved at 1.5 Å. The present study reveals a previously unknown key role for conserved Glu46, Phe145 and Met205 and Gln236, Pro234 and Ala233 residues, with the latter three being located in the flexible substrate-covering loop. Gln236 was shown to be responsible for the folding of this loop and for the dramatic reduction of its flexibility, which triggers active site closure. Glu46 was found to be key in bringing the substrate close to the lysine/histidine catalytic pocket to initiate catalysis. The present study could be useful in the rational design of inhibitors of this challenging and recognized target for the development of novel herbicides and antimicrobial agents.

Topological distortion and reorganized modular structure of gut microbial co-occurrence networks in inflammatory bowel disease

NASA Astrophysics Data System (ADS)

Baldassano, Steven N.; Bassett, Danielle S.

2016-05-01

The gut microbiome plays a key role in human health, and alterations of the normal gut flora are associated with a variety of distinct disease states. Yet, the natural dependencies between microbes in healthy and diseased individuals remain far from understood. Here we use a network-based approach to characterize microbial co-occurrence in individuals with inflammatory bowel disease (IBD) and healthy (non-IBD control) individuals. We find that microbial networks in patients with IBD differ in both global structure and local connectivity patterns. While a “core” microbiome is preserved, network topology of other densely interconnected microbe modules is distorted, with potent inflammation-mediating organisms assuming roles as integrative and highly connected inter-modular hubs. We show that while both networks display a rich-club organization, in which a small set of microbes commonly co-occur, the healthy network is more easily disrupted by elimination of a small number of key species. Further investigation of network alterations in disease might offer mechanistic insights into the specific pathogens responsible for microbiome-mediated inflammation in IBD.

Group precipitation and age hardening of nanostructured Fe-based alloys with ultra-high strengths

DOE PAGES

Jiao, Z. B.; Luan, J. H.; Miller, M. K.; ...

2016-02-19

The precipitation of nanoparticles plays a key role in determining the properties of many structural materials, and the understanding of their formation and stabilization mechanisms has been a long standing interest in the material field. However, the critical issues involving the group precipitation of various nanoparticles and their cooperative hardening mechanism remain elusive in the newly discovered Fe-based alloys with nanostructures. Here we quantitatively elucidate the nucleation mechanism, evolution kinetics and hardening effects of the group-precipitated nanoparticles in the Fe-Cu-Ni-Al-based alloys by atom probe tomography together with both first-principles and thermodynamic calculations. Our results provide the compelling evidence for twomore » interesting but complex group precipitation pathways of nanoparticles, i.e., the Cu-rich and NiAl-based precipitations. Lastly, the co-existence of the two precipitation pathways plays a key role in age hardening kinetics and ultimately enhances the hardening response, as compared to the single particle type of strengthening, therefore providing an effective new approach for strengthening materials for structural applications.« less

Group precipitation and age hardening of nanostructured Fe-based alloys with ultra-high strengths

PubMed Central

Jiao, Z. B.; Luan, J. H.; Miller, M. K.; Yu, C. Y.; Liu, C. T.

2016-01-01

The precipitation of nanoparticles plays a key role in determining the properties of many structural materials, and the understanding of their formation and stabilization mechanisms has been a long standing interest in the material field. However, the critical issues involving the group precipitation of various nanoparticles and their cooperative hardening mechanism remain elusive in the newly discovered Fe-based alloys with nanostructures. Here we quantitatively elucidate the nucleation mechanism, evolution kinetics and hardening effects of the group-precipitated nanoparticles in the Fe-Cu-Ni-Al-based alloys by atom probe tomography together with both first-principles and thermodynamic calculations. Our results provide the compelling evidence for two interesting but complex group precipitation pathways of nanoparticles, i.e., the Cu-rich and NiAl-based precipitations. The co-existence of the two precipitation pathways plays a key role in age hardening kinetics and ultimately enhances the hardening response, as compared to the single particle type of strengthening, therefore providing an effective new approach for strengthening materials for structural applications. PMID:26892834

Confirming the key role of Ar+ ion bombardment in the growth feature of nanostructured carbon materials by PECVD

NASA Astrophysics Data System (ADS)

Liu, Yulin; Lin, Jinghuang; Jia, Henan; Chen, Shulin; Qi, Junlei; Qu, Chaoqun; Cao, Jian; Feng, Jicai; Fei, Weidong

2017-11-01

In order to confirm the key role of Ar+ ion bombardment in the growth feature of nanostructured carbon materials (NCMs), here we report a novel strategy to create different Ar+ ion states in situ in plasma enhanced chemical vapor deposition (PECVD) by separating catalyst film from the substrate. Different bombardment environments on either side of the catalyst film were created simultaneously to achieve multi-layered structural NCMs. Results showed that Ar+ ion bombardment is crucial and complex for the growth of NCMs. Firstly, Ar+ ion bombardment has both positive and negative effects on carbon nanotubes (CNTs). On one hand, Ar+ ions can break up the graphic structure of CNTs and suppress thin CNT nucleation and growth. On the other hand, Ar+ ion bombardment can remove redundant carbon layers on the surface of large catalyst particles which is essential for thick CNTs. As a result, the diameter of the CNTs depends on the Ar+ ion state. As for vertically oriented few-layer graphene (VFG), Ar+ ions are essential and can even convert the CNTs into VFG. Therefore, by combining with the catalyst separation method, specific or multi-layered structural NCMs can be obtained by PECVD only by changing the intensity of Ar+ ion bombardment, and these special NCMs are promising in many fields.

Bacterial cellulose biosynthesis: diversity of operons, subunits, products, and functions.

PubMed

Römling, Ute; Galperin, Michael Y

2015-09-01

Recent studies of bacterial cellulose biosynthesis, including structural characterization of a functional cellulose synthase complex, provided the first mechanistic insight into this fascinating process. In most studied bacteria, just two subunits, BcsA and BcsB, are necessary and sufficient for the formation of the polysaccharide chain in vitro. Other subunits - which differ among various taxa - affect the enzymatic activity and product yield in vivo by modulating (i) the expression of the biosynthesis apparatus, (ii) the export of the nascent β-D-glucan polymer to the cell surface, and (iii) the organization of cellulose fibers into a higher-order structure. These auxiliary subunits play key roles in determining the quantity and structure of resulting biofilms, which is particularly important for the interactions of bacteria with higher organisms - leading to rhizosphere colonization and modulating the virulence of cellulose-producing bacterial pathogens inside and outside of host cells. We review the organization of four principal types of cellulose synthase operon found in various bacterial genomes, identify additional bcs genes that encode components of the cellulose biosynthesis and secretion machinery, and propose a unified nomenclature for these genes and subunits. We also discuss the role of cellulose as a key component of biofilms and in the choice between acute infection and persistence in the host. Copyright © 2015 Elsevier Ltd. All rights reserved.

Confirming the key role of Ar+ ion bombardment in the growth feature of nanostructured carbon materials by PECVD.

PubMed

Liu, Yulin; Lin, Jinghuang; Jia, Henan; Chen, Shulin; Qi, Junlei; Qu, Chaoqun; Cao, Jian; Feng, Jicai; Fei, Weidong

2017-11-24

In order to confirm the key role of Ar + ion bombardment in the growth feature of nanostructured carbon materials (NCMs), here we report a novel strategy to create different Ar + ion states in situ in plasma enhanced chemical vapor deposition (PECVD) by separating catalyst film from the substrate. Different bombardment environments on either side of the catalyst film were created simultaneously to achieve multi-layered structural NCMs. Results showed that Ar + ion bombardment is crucial and complex for the growth of NCMs. Firstly, Ar + ion bombardment has both positive and negative effects on carbon nanotubes (CNTs). On one hand, Ar + ions can break up the graphic structure of CNTs and suppress thin CNT nucleation and growth. On the other hand, Ar + ion bombardment can remove redundant carbon layers on the surface of large catalyst particles which is essential for thick CNTs. As a result, the diameter of the CNTs depends on the Ar + ion state. As for vertically oriented few-layer graphene (VFG), Ar + ions are essential and can even convert the CNTs into VFG. Therefore, by combining with the catalyst separation method, specific or multi-layered structural NCMs can be obtained by PECVD only by changing the intensity of Ar + ion bombardment, and these special NCMs are promising in many fields.

Obesity resistance and deregulation of lipogenesis in Δ6-fatty acid desaturase (FADS2) deficiency.

PubMed

Stoffel, Wilhelm; Hammels, Ina; Jenke, Britta; Binczek, Erika; Schmidt-Soltau, Inga; Brodesser, Susanne; Odenthal, Margarete; Thevis, Mario

2014-01-01

Δ-6-fatty acid desaturase (FADS2) is the key enzyme in the biosynthesis of polyunsaturated fatty acids (PUFAs), the essential structural determinants of mammalian membrane lipid-bilayers. We developed the auxotrophic fads2(-/-) mouse mutant to assess the enigmatic role of ω3- and ω6-PUFAs in lipid homeostasis, membrane structure and function. Obesity resistance is another major phenotype of the fads2(-/-) mutant, the molecular basis of which is unknown. Phospholipidomic profiling of membrane systems of fads2(-/-)mice revealed diacylglycerol-structures, deprived of PUFAs but substituted with surrogate eicosa-5,11,14-trienoic acid. ω6-Arachidonic (AA) and ω3-docosahexaenoic acid (DHA) supplemented diets transformed fads2(-/-) into AA-fads2(-/-) and DHA-fads2(-/-) mutants. Severely altered phospholipid-bilayer structures of subcellular membranes of fads2(-/-) liver specifically interfered with maturation of transcription factor sterol-regulatory-element-binding protein, the key regulator of lipogenesis and lipid homeostasis. This study strengthens the concept that specific PUFA-substituted membrane phospholipid species are critical constituents of the structural platform operative in lipid homeostasis in normal and disease conditions.

The structure of mouse cytomegalovirus m04 protein obtained from sparse NMR data reveals a conserved fold of the m02-m06 viral immune modulator family.

PubMed

Sgourakis, Nikolaos G; Natarajan, Kannan; Ying, Jinfa; Vogeli, Beat; Boyd, Lisa F; Margulies, David H; Bax, Ad

2014-09-02

Immunoevasins are key proteins used by viruses to subvert host immune responses. Determining their high-resolution structures is key to understanding virus-host interactions toward the design of vaccines and other antiviral therapies. Mouse cytomegalovirus encodes a unique set of immunoevasins, the m02-m06 family, that modulates major histocompatibility complex class I (MHC-I) antigen presentation to CD8+ T cells and natural killer cells. Notwithstanding the large number of genetic and functional studies, the structural biology of immunoevasins remains incompletely understood, largely because of crystallization bottlenecks. Here we implement a technology using sparse nuclear magnetic resonance data and integrative Rosetta modeling to determine the structure of the m04/gp34 immunoevasin extracellular domain. The structure reveals a β fold that is representative of the m02-m06 family of viral proteins, several of which are known to bind MHC-I molecules and interfere with antigen presentation, suggesting its role as a diversified immune regulation module. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structure and Self-Assembly of the Calcium Binding Matrix Protein of Human Metapneumovirus

PubMed Central

Leyrat, Cedric; Renner, Max; Harlos, Karl; Huiskonen, Juha T.; Grimes, Jonathan M.

2014-01-01

Summary The matrix protein (M) of paramyxoviruses plays a key role in determining virion morphology by directing viral assembly and budding. Here, we report the crystal structure of the human metapneumovirus M at 2.8 Å resolution in its native dimeric state. The structure reveals the presence of a high-affinity Ca2+ binding site. Molecular dynamics simulations (MDS) predict a secondary lower-affinity site that correlates well with data from fluorescence-based thermal shift assays. By combining small-angle X-ray scattering with MDS and ensemble analysis, we captured the structure and dynamics of M in solution. Our analysis reveals a large positively charged patch on the protein surface that is involved in membrane interaction. Structural analysis of DOPC-induced polymerization of M into helical filaments using electron microscopy leads to a model of M self-assembly. The conservation of the Ca2+ binding sites suggests a role for calcium in the replication and morphogenesis of pneumoviruses. PMID:24316400

Structure of the full-length glucagon class B G protein-coupled receptor

PubMed Central

Zhang, Haonan; Qiao, Anna; Yang, Dehua; Yang, Linlin; Dai, Antao; de Graaf, Chris; Reedtz-Runge, Steffen; Dharmarajan, Venkatasubramanian; Zhang, Hui; Han, Gye Won; Grant, Thomas D.; Sierra, Raymond G.; Weierstall, Uwe; Nelson, Garrett; Liu, Wei; Wu, Yanhong; Ma, Limin; Cai, Xiaoqing; Lin, Guangyao; Wu, Xiaoai; Geng, Zhi; Dong, Yuhui; Song, Gaojie; Griffin, Patrick R.; Lau, Jesper; Cherezov, Vadim; Yang, Huaiyu; Hanson, Michael A.; Stevens, Raymond C.; Zhao, Qiang; Jiang, Hualiang; Wang, Ming-Wei; Wu, Beili

2017-01-01

The human glucagon receptor (GCGR) belongs to the class B G protein-coupled receptor (GPCR) family and plays a key role in glucose homeostasis and the pathophysiology of type 2 diabetes. Here we report the 3.0 Å crystal structure of full-length GCGR containing both extracellular domain (ECD) and transmembrane domain (TMD) in an inactive conformation. The two domains are connected by a 12-residue segment termed the ‘stalk’, which adopts a β-strand conformation, instead of forming an α-helix as observed in the previously solved structure of GCGR-TMD. The first extracellular loop (ECL1) exhibits a β-hairpin conformation and interacts with the stalk to form a compact β-sheet structure. Hydrogen/deuterium exchange, disulfide cross-linking and molecular dynamics studies suggest that the stalk and ECL1 play critical roles in modulating peptide ligand binding and receptor activation. These insights into the full-length GCGR structure deepen our understanding about the signaling mechanisms of class B GPCRs. PMID:28514451

Free-energy simulations reveal molecular mechanism for functional switch of a DNA helicase

PubMed Central

Ma, Wen; Whitley, Kevin D; Schulten, Klaus

2018-01-01

Helicases play key roles in genome maintenance, yet it remains elusive how these enzymes change conformations and how transitions between different conformational states regulate nucleic acid reshaping. Here, we developed a computational technique combining structural bioinformatics approaches and atomic-level free-energy simulations to characterize how the Escherichia coli DNA repair enzyme UvrD changes its conformation at the fork junction to switch its function from unwinding to rezipping DNA. The lowest free-energy path shows that UvrD opens the interface between two domains, allowing the bound ssDNA to escape. The simulation results predict a key metastable 'tilted' state during ssDNA strand switching. By simulating FRET distributions with fluorophores attached to UvrD, we show that the new state is supported quantitatively by single-molecule measurements. The present study deciphers key elements for the 'hyper-helicase' behavior of a mutant and provides an effective framework to characterize directly structure-function relationships in molecular machines. PMID:29664402

Free-energy simulations reveal molecular mechanism for functional switch of a DNA helicase.

PubMed

Ma, Wen; Whitley, Kevin D; Chemla, Yann R; Luthey-Schulten, Zaida; Schulten, Klaus

2018-04-17

Helicases play key roles in genome maintenance, yet it remains elusive how these enzymes change conformations and how transitions between different conformational states regulate nucleic acid reshaping. Here, we developed a computational technique combining structural bioinformatics approaches and atomic-level free-energy simulations to characterize how the Escherichia coli DNA repair enzyme UvrD changes its conformation at the fork junction to switch its function from unwinding to rezipping DNA. The lowest free-energy path shows that UvrD opens the interface between two domains, allowing the bound ssDNA to escape. The simulation results predict a key metastable 'tilted' state during ssDNA strand switching. By simulating FRET distributions with fluorophores attached to UvrD, we show that the new state is supported quantitatively by single-molecule measurements. The present study deciphers key elements for the 'hyper-helicase' behavior of a mutant and provides an effective framework to characterize directly structure-function relationships in molecular machines. © 2018, Ma et al.

Fun with maths: exploring implications of mathematical models for malaria eradication.

PubMed

Eckhoff, Philip A; Bever, Caitlin A; Gerardin, Jaline; Wenger, Edward A

2014-12-11

Mathematical analyses and modelling have an important role informing malaria eradication strategies. Simple mathematical approaches can answer many questions, but it is important to investigate their assumptions and to test whether simple assumptions affect the results. In this note, four examples demonstrate both the effects of model structures and assumptions and also the benefits of using a diversity of model approaches. These examples include the time to eradication, the impact of vaccine efficacy and coverage, drug programs and the effects of duration of infections and delays to treatment, and the influence of seasonality and migration coupling on disease fadeout. An excessively simple structure can miss key results, but simple mathematical approaches can still achieve key results for eradication strategy and define areas for investigation by more complex models.

Orbital selective pairing and gap structures of iron-based superconductors

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

Kreisel, Andreas; Andersen, Brian M.; Sprau, P. O.

We discuss the in uence on spin-fluctuation pairing theory of orbital selective strong correlation effects in Fe-based superconductors, particularly Fe chalcogenide systems. We propose that a key ingredient for an improved itinerant pairing theory is orbital selectivity, i.e., incorporating the reduced coherence of quasiparticles occupying specific orbital states. This modifies the usual spin-fluctuation via suppression of pair scattering processes involving those less coherent states and results in orbital selective Cooper pairing of electrons in the remaining states. We show that this paradigm yields remarkably good agreement with the experimentally observed anisotropic gap structures in both bulk and monolayer FeSe, asmore » well as LiFeAs, indicating that orbital selective Cooper pairing plays a key role in the more strongly correlated iron-based superconductors.« less

Orbital selective pairing and gap structures of iron-based superconductors

DOE PAGES

Kreisel, Andreas; Andersen, Brian M.; Sprau, P. O.; ...

2017-05-08

We discuss the in uence on spin-fluctuation pairing theory of orbital selective strong correlation effects in Fe-based superconductors, particularly Fe chalcogenide systems. We propose that a key ingredient for an improved itinerant pairing theory is orbital selectivity, i.e., incorporating the reduced coherence of quasiparticles occupying specific orbital states. This modifies the usual spin-fluctuation via suppression of pair scattering processes involving those less coherent states and results in orbital selective Cooper pairing of electrons in the remaining states. We show that this paradigm yields remarkably good agreement with the experimentally observed anisotropic gap structures in both bulk and monolayer FeSe, asmore » well as LiFeAs, indicating that orbital selective Cooper pairing plays a key role in the more strongly correlated iron-based superconductors.« less

Establishing a nurse practitioner collaborative: evolution, development, and outcomes.

PubMed

Quinn, Karen; Hudson, Peter

2014-09-01

The first Australian palliative care nurse practitioner (NP) was endorsed in 2003. In 2009 the Victoria Department of Health funded the development of the Victorian Palliative Care Nurse Practitioner Collaborative (VPCNPC). Its aim was to promote the NP role, develop resources, and provide education and mentorship to NPs, nurse practitioner candidates (NPCs), and health service managers. Four key objectives were developed: identify the demographic profile of palliative care NPCs in Victoria; develop an education curriculum and practical resources to support the training and education of palliative care NPCs and NPs; provide mentorship to NPs, NPCs, and service managers; and ensure effective communication with all key stakeholders. An NPC survey was also conducted to explore NPC demographics, models of care, the hours of study required for the role, the mentoring process, and education needs. This paper reports on the establishment of the VPCNPC, the steps taken to achieve its objectives, and the results of the survey. The NP role in palliative care in Australia continues to evolve, and the VPCNPC provides a structure and resources to clearly articulate the benefits of the role to nursing and clinical services.

Roles and responsibilities of pharmacists with respect to natural health products: key informant interviews.

PubMed

Olatunde, Shade; Boon, Heather; Hirschkorn, Kristine; Welsh, Sandy; Bajcar, Jana

2010-03-01

Although many pharmacies sell natural health products (NHPs), there is no clear definition as to the roles and responsibilities (if any) of pharmacists with respect to these products. The purpose of this study was to explore pharmacy and stakeholder leaders' perceptions of pharmacists' professional NHP roles and responsibilities. Semi-structured key informant interviews were conducted with pharmacy leaders (n=17) and stakeholder (n=18) leaders representing consumers, complementary and alternative medicine practitioners, conventional health care practitioners, and industry across Canada. All participants believed a main NHP responsibility for pharmacists was in safety monitoring, although a one challenge identified in the interviews was pharmacists' general lack of NHP knowledge; however, stakeholder leaders did not expect pharmacists to be experts, but should have a basic level of knowledge about NHPs. Participants described pharmacists' professional roles and responsibilities for NHPs as similar to those for over-the-counter drugs; more awareness of existing NHP-related pharmacy policies is needed, and pharmacy owners/managers should provide additional training to ensure front-line pharmacists have appropriate knowledge of NHPs sold in the pharmacy. Copyright 2010 Elsevier Inc. All rights reserved.

X-ray crystal structure of plasmin with tranexamic acid-derived active site inhibitors.

PubMed

Law, Ruby H P; Wu, Guojie; Leung, Eleanor W W; Hidaka, Koushi; Quek, Adam J; Caradoc-Davies, Tom T; Jeevarajah, Devadharshini; Conroy, Paul J; Kirby, Nigel M; Norton, Raymond S; Tsuda, Yuko; Whisstock, James C

2017-05-09

The zymogen protease plasminogen and its active form plasmin perform key roles in blood clot dissolution, tissue remodeling, cell migration, and bacterial pathogenesis. Dysregulation of the plasminogen/plasmin system results in life-threatening hemorrhagic disorders or thrombotic vascular occlusion. Accordingly, inhibitors of this system are clinically important. Currently, tranexamic acid (TXA), a molecule that prevents plasminogen activation through blocking recruitment to target substrates, is the most widely used inhibitor for the plasminogen/plasmin system in therapeutics. However, TXA lacks efficacy on the active form of plasmin. Thus, there is a need to develop specific inhibitors that target the protease active site. Here we report the crystal structures of plasmin in complex with the novel YO ( trans -4-aminomethylcyclohexanecarbonyl-l-tyrosine- n -octylamide) class of small molecule inhibitors. We found that these inhibitors form key interactions with the S1 and S3' subsites of the catalytic cleft. Here, the TXA moiety of the YO compounds inserts into the primary (S1) specificity pocket, suggesting that TXA itself may function as a weak plasmin inhibitor, a hypothesis supported by subsequent biochemical and biophysical analyses. Mutational studies reveal that F587 of the S' subsite plays a key role in mediating the inhibitor interaction. Taken together, these data provide a foundation for the future development of small molecule inhibitors to specifically regulate plasmin function in a range of diseases and disorders.

X-ray crystal structure of plasmin with tranexamic acid–derived active site inhibitors

PubMed Central

Wu, Guojie; Leung, Eleanor W. W.; Hidaka, Koushi; Quek, Adam J.; Caradoc-Davies, Tom T.; Jeevarajah, Devadharshini; Kirby, Nigel M.; Norton, Raymond S.; Tsuda, Yuko; Whisstock, James C.

2017-01-01

The zymogen protease plasminogen and its active form plasmin perform key roles in blood clot dissolution, tissue remodeling, cell migration, and bacterial pathogenesis. Dysregulation of the plasminogen/plasmin system results in life-threatening hemorrhagic disorders or thrombotic vascular occlusion. Accordingly, inhibitors of this system are clinically important. Currently, tranexamic acid (TXA), a molecule that prevents plasminogen activation through blocking recruitment to target substrates, is the most widely used inhibitor for the plasminogen/plasmin system in therapeutics. However, TXA lacks efficacy on the active form of plasmin. Thus, there is a need to develop specific inhibitors that target the protease active site. Here we report the crystal structures of plasmin in complex with the novel YO (trans-4-aminomethylcyclohexanecarbonyl-l-tyrosine-n-octylamide) class of small molecule inhibitors. We found that these inhibitors form key interactions with the S1 and S3′ subsites of the catalytic cleft. Here, the TXA moiety of the YO compounds inserts into the primary (S1) specificity pocket, suggesting that TXA itself may function as a weak plasmin inhibitor, a hypothesis supported by subsequent biochemical and biophysical analyses. Mutational studies reveal that F587 of the S′ subsite plays a key role in mediating the inhibitor interaction. Taken together, these data provide a foundation for the future development of small molecule inhibitors to specifically regulate plasmin function in a range of diseases and disorders. PMID:29296720

HDAPD: a web tool for searching the disease-associated protein structures

PubMed Central

2010-01-01

Background The protein structures of the disease-associated proteins are important for proceeding with the structure-based drug design to against a particular disease. Up until now, proteins structures are usually searched through a PDB id or some sequence information. However, in the HDAPD database presented here the protein structure of a disease-associated protein can be directly searched through the associated disease name keyed in. Description The search in HDAPD can be easily initiated by keying some key words of a disease, protein name, protein type, or PDB id. The protein sequence can be presented in FASTA format and directly copied for a BLAST search. HDAPD is also interfaced with Jmol so that users can observe and operate a protein structure with Jmol. The gene ontological data such as cellular components, molecular functions, and biological processes are provided once a hyperlink to Gene Ontology (GO) is clicked. Further, HDAPD provides a link to the KEGG map such that where the protein is placed and its relationship with other proteins in a metabolic pathway can be found from the map. The latest literatures namely titles, journals, authors, and abstracts searched from PubMed for the protein are also presented as a length controllable list. Conclusions Since the HDAPD data content can be routinely updated through a PHP-MySQL web page built, the new database presented is useful for searching the structures for some disease-associated proteins that may play important roles in the disease developing process for performing the structure-based drug design to against the diseases. PMID:20158919

Demystifying Mechanosensitive Piezo Ion Channels.

PubMed

Xu, X Z Shawn

2016-06-01

Mechanosensitive channels mediate touch, hearing, proprioception, and blood pressure regulation. Piezo proteins, including Piezo1 and Piezo2, represent a new class of mechanosensitive channels that have been reported to play key roles in most, if not all, of these modalities. The structural architecture and molecular mechanisms by which Piezos act as mechanosensitive channels, however, remain mysterious. Two new studies have now provided critical insights into the atomic structure and molecular basis of the ion permeation and mechano-gating properties of the Piezo1 channel.

Evolution or revolution? New committee to play key role in determining pace of change at CMA

PubMed Central

Rafuse, Jill

1995-01-01

The CMA's relationship with its provincial and territorial divisions, affiliate societies and Canada's 60 000 physicians is under the microscope as a newly formed Committee on Structure prepares a white paper on organization and governance options. The document, which will soon be circulated for discussion and feedback, will lead to recommendations for a revitalized structure to make the CMA a more efficient organization that is more responsive to members' needs. Imagesp96-a

The discovery of the structure of DNA

NASA Astrophysics Data System (ADS)

Squires, G. L.

2003-04-01

On 25 April 1953, Nature published a letter by Francis Crick and James Watson, at the Cavendish Laboratory, Cambridge, proposing a structure for DNA. This letter marked the beginning of a revolution in biology. Besides Crick and Watson, two other scientists, Rosalind Franklin and Maurice Wilkins, played key roles in the discovery. After sketching the early careers of the four scientists, the present article gives an account of the physics and chemistry involved in the discovery, and the events leading up to it.

Wybutosine biosynthesis: Structural and mechanistic overview

PubMed Central

Perche-Letuvée, Phanélie; Molle, Thibaut; Forouhar, Farhad; Mulliez, Etienne; Atta, Mohamed

2014-01-01

Over the last 10 years, significant progress has been made in understanding the genetics, enzymology and structural components of the wybutosine (yW) biosynthetic pathway. These studies have played a key role in expanding our understanding of yW biosynthesis and have revealed unexpected evolutionary ties, which are presently being unraveled. The enzymes catalyzing the 5 steps of this pathway, from genetically encoded guanosine to wybutosine base, provide an ensemble of amazing reaction mechanisms that are to be discussed in this review article. PMID:25629788

Molecular Evidence of Stress-Induced Acute Heart Injury in a Mouse Model Simulating Posttraumatic Stress Disorder

DTIC Science & Technology

2014-02-25

risk of drug or alcohol abuse. In addition, patients with PTSD often display structural changes in the pre- frontal cortex, the amygdala, and the... triglyceride levels (12–15). An 1871 report noted that serious cardiac disorders (car- diomyopathies, heart failure, heart pain, etc.) were a consequence of...epicardium probably play a key role in the EMT process (30, 31). Maintaining the proper ECM structure is critical to pre- serving the architecture and

Structural Integrity of the Greek Key Motif in βγ-Crystallins Is Vital for Central Eye Lens Transparency

PubMed Central

Vendra, Venkata Pulla Rao; Agarwal, Garima; Chandani, Sushil; Talla, Venu; Srinivasan, Narayanaswamy; Balasubramanian, Dorairajan

2013-01-01

Background We highlight an unrecognized physiological role for the Greek key motif, an evolutionarily conserved super-secondary structural topology of the βγ-crystallins. These proteins constitute the bulk of the human eye lens, packed at very high concentrations in a compact, globular, short-range order, generating transparency. Congenital cataract (affecting 400,000 newborns yearly worldwide), associated with 54 mutations in βγ-crystallins, occurs in two major phenotypes nuclear cataract, which blocks the central visual axis, hampering the development of the growing eye and demanding earliest intervention, and the milder peripheral progressive cataract where surgery can wait. In order to understand this phenotypic dichotomy at the molecular level, we have studied the structural and aggregation features of representative mutations. Methods Wild type and several representative mutant proteins were cloned, expressed and purified and their secondary and tertiary structural details, as well as structural stability, were compared in solution, using spectroscopy. Their tendencies to aggregate in vitro and in cellulo were also compared. In addition, we analyzed their structural differences by molecular modeling in silico. Results Based on their properties, mutants are seen to fall into two classes. Mutants A36P, L45PL54P, R140X, and G165fs display lowered solubility and structural stability, expose several buried residues to the surface, aggregate in vitro and in cellulo, and disturb/distort the Greek key motif. And they are associated with nuclear cataract. In contrast, mutants P24T and R77S, associated with peripheral cataract, behave quite similar to the wild type molecule, and do not affect the Greek key topology. Conclusion When a mutation distorts even one of the four Greek key motifs, the protein readily self-aggregates and precipitates, consistent with the phenotype of nuclear cataract, while mutations not affecting the motif display ‘native state aggregation’, leading to peripheral cataract, thus offering a protein structural rationale for the cataract phenotypic dichotomy “distort motif, lose central vision”. PMID:23936409

Tailored combination prevention packages and PrEP for young key populations

PubMed Central

Pettifor, Audrey; Nguyen, Nadia L; Celum, Connie; Cowan, Frances M; Go, Vivian; Hightow-Weidman, Lisa

2015-01-01

Introduction Young key populations, defined in this article as men who have sex with men, transgender persons, people who sell sex and people who inject drugs, are at particularly high risk for HIV. Due to the often marginalized and sometimes criminalized status of young people who identify as members of key populations, there is a need for HIV prevention packages that account for the unique and challenging circumstances they face. Pre-exposure prophylaxis (PrEP) is likely to become an important element of combination prevention for many young key populations. Objective In this paper, we discuss important challenges to HIV prevention among young key populations, identify key components of a tailored combination prevention package for this population and examine the role of PrEP in these prevention packages. Methods We conducted a comprehensive review of the evidence to date on prevention strategies, challenges to prevention and combination prevention packages for young key populations. We focused specifically on the role of PrEP in these prevention packages and on young people under the age of 24, and 18 in particular. Results and discussion Combination prevention packages that include effective, acceptable and scalable behavioural, structural and biologic interventions are needed for all key populations to prevent new HIV infections. Interventions in these packages should meaningfully involve beneficiaries in the design and implementation of the intervention, and take into account the context in which the intervention is being delivered to thoughtfully address issues of stigma and discrimination. These interventions will likely be most effective if implemented in conjunction with strategies to facilitate an enabling environment, including increasing access to HIV testing and health services for PrEP and other prevention strategies, decriminalizing key populations’ practices, increasing access to prevention and care, reducing stigma and discrimination, and fostering community empowerment. PrEP could offer a highly effective, time-limited primary prevention for young key populations if it is implemented in combination with other programs to increase access to health services and encourage the reliable use of PrEP while at risk of HIV exposure. Conclusions Reductions in HIV incidence will only be achieved through the implementation of combinations of interventions that include biomedical and behavioural interventions, as well as components that address social, economic and other structural factors that influence HIV prevention and transmission. PMID:25724507

The bioactive acidic serine- and aspartate-rich motif peptide.

PubMed

Minamizaki, Tomoko; Yoshiko, Yuji

2015-01-01

The organic component of the bone matrix comprises 40% dry weight of bone. The organic component is mostly composed of type I collagen and small amounts of non-collagenous proteins (NCPs) (10-15% of the total bone protein content). The small integrin-binding ligand N-linked glycoprotein (SIBLING) family, a NCP, is considered to play a key role in bone mineralization. SIBLING family of proteins share common structural features and includes the arginine-glycine-aspartic acid (RGD) motif and acidic serine- and aspartic acid-rich motif (ASARM). Clinical manifestations of gene mutations and/or genetically modified mice indicate that SIBLINGs play diverse roles in bone and extraskeletal tissues. ASARM peptides might not be primary responsible for the functional diversity of SIBLINGs, but this motif is suggested to be a key domain of SIBLINGs. However, the exact function of ASARM peptides is poorly understood. In this article, we discuss the considerable progress made in understanding the role of ASARM as a bioactive peptide.

Scalable and Axiomatic Ranking of Network Role Similarity

PubMed Central

Jin, Ruoming; Lee, Victor E.; Li, Longjie

2014-01-01

A key task in analyzing social networks and other complex networks is role analysis: describing and categorizing nodes according to how they interact with other nodes. Two nodes have the same role if they interact with equivalent sets of neighbors. The most fundamental role equivalence is automorphic equivalence. Unfortunately, the fastest algorithms known for graph automorphism are nonpolynomial. Moreover, since exact equivalence is rare, a more meaningful task is measuring the role similarity between any two nodes. This task is closely related to the structural or link-based similarity problem that SimRank addresses. However, SimRank and other existing similarity measures are not sufficient because they do not guarantee to recognize automorphically or structurally equivalent nodes. This paper makes two contributions. First, we present and justify several axiomatic properties necessary for a role similarity measure or metric. Second, we present RoleSim, a new similarity metric which satisfies these axioms and which can be computed with a simple iterative algorithm. We rigorously prove that RoleSim satisfies all these axiomatic properties. We also introduce Iceberg RoleSim, a scalable algorithm which discovers all pairs with RoleSim scores above a user-defined threshold θ. We demonstrate the interpretative power of RoleSim on both both synthetic and real datasets. PMID:25383066

Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors activate the aryl hydrocarbon receptor

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

Moyer, Benjamin J.

Indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in the immune system by regulating tryptophan levels and T cell differentiation. Several tumor types overexpress IDO1 to avoid immune surveillance making IDO1 of interest as a target for therapeutic intervention. As a result, several IDO1 inhibitors are currently being tested in clinical trials for cancer treatment as well as several other diseases. Many of the IDO1 inhibitors in clinical trials naturally bear structural similarities to the IDO1 substrate tryptophan, as such, they fulfill many of the structural and functional criteria as potential AHR ligands. Using mouse and human cell-based luciferase genemore » reporter assays, qPCR confirmation experiments, and CYP1A1 enzyme activity assays, we report that some of the promising clinical IDO1 inhibitors also act as agonists for the aryl hydrocarbon receptor (AHR), best known for its roles in xenobiotic metabolism and as another key regulator of the immune response. The dual role as IDO antagonist and AHR agonist for many of these IDO target drugs should be considered for full interrogation of their biological mechanisms and clinical outcomes. - Highlights: • Indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors are in cancer clinical trials. • Some IDO1 inhibitors also potently activate AHR signaling. • The dual role of the IDO1 inhibitors may explain some past paradoxical findings. • AHR induction studies must be included in assessing clinical suitability.« less

Re-analysis of correlations among four impulsivity scales.

PubMed

Gallardo-Pujol, David; Andrés-Pueyo, Antonio

2006-08-01

Impulsivity plays a key role in normal and pathological behavior. Although there is some consensus about its conceptualization, there have been many attempts to build a multidimensional tool due to the lack of agreement in how to measure it. A recent study claimed support for a three-dimensional structure of impulsivity, however with weak empirical support. By re-analysing those data, a four-factor structure was found to describe the correlation matrix much better. The debate remains open and further research is needed to clarify the factor structure. The desirability of constructing new measures, perhaps analogously to the Wechsler Intelligence Scale, is emphasized.

The role of dispersal mode and habitat specialization for metacommunity structure of shallow beach invertebrates.

PubMed

Rodil, Iván F; Lucena-Moya, Paloma; Jokinen, Henri; Ollus, Victoria; Wennhage, Håkan; Villnäs, Anna; Norkko, Alf

2017-01-01

Metacommunity ecology recognizes the interplay between local and regional patterns in contributing to spatial variation in community structure. In aquatic systems, the relative importance of such patterns depends mainly on the potential connectivity of the specific system. Thus, connectivity is expected to increase in relation to the degree of water movement, and to depend on the specific traits of the study organism. We examined the role of environmental and spatial factors in structuring benthic communities from a highly connected shallow beach network using a metacommunity approach. Both factors contributed to a varying degree to the structure of the local communities suggesting that environmental filters and dispersal-related mechanisms played key roles in determining abundance patterns. We categorized benthic taxa according to their dispersal mode (passive vs. active) and habitat specialization (generalist vs. specialist) to understand the relative importance of environment and dispersal related processes for shallow beach metacommunities. Passive dispersers were predicted by a combination of environmental and spatial factors, whereas active dispersers were not spatially structured and responded only to local environmental factors. Generalists were predicted primarily by spatial factors, while specialists were only predicted by local environmental factors. The results suggest that the role of the spatial component in metacommunity organization is greater in open coastal waters, such as shallow beaches, compared to less-connected environmentally controlled aquatic systems. Our results also reveal a strong environmental role in structuring the benthic metacommunity of shallow beaches. Specifically, we highlight the sensitivity of shallow beach macrofauna to environmental factors related to eutrophication proxies.

The role of dispersal mode and habitat specialization for metacommunity structure of shallow beach invertebrates

PubMed Central

Lucena-Moya, Paloma; Jokinen, Henri; Ollus, Victoria; Wennhage, Håkan; Villnäs, Anna; Norkko, Alf

2017-01-01

Metacommunity ecology recognizes the interplay between local and regional patterns in contributing to spatial variation in community structure. In aquatic systems, the relative importance of such patterns depends mainly on the potential connectivity of the specific system. Thus, connectivity is expected to increase in relation to the degree of water movement, and to depend on the specific traits of the study organism. We examined the role of environmental and spatial factors in structuring benthic communities from a highly connected shallow beach network using a metacommunity approach. Both factors contributed to a varying degree to the structure of the local communities suggesting that environmental filters and dispersal-related mechanisms played key roles in determining abundance patterns. We categorized benthic taxa according to their dispersal mode (passive vs. active) and habitat specialization (generalist vs. specialist) to understand the relative importance of environment and dispersal related processes for shallow beach metacommunities. Passive dispersers were predicted by a combination of environmental and spatial factors, whereas active dispersers were not spatially structured and responded only to local environmental factors. Generalists were predicted primarily by spatial factors, while specialists were only predicted by local environmental factors. The results suggest that the role of the spatial component in metacommunity organization is greater in open coastal waters, such as shallow beaches, compared to less-connected environmentally controlled aquatic systems. Our results also reveal a strong environmental role in structuring the benthic metacommunity of shallow beaches. Specifically, we highlight the sensitivity of shallow beach macrofauna to environmental factors related to eutrophication proxies. PMID:28196112

Societal and Family Situations in the U.S.A. That Affect Children's Pro-Social Behavior.

ERIC Educational Resources Information Center

Jambor, Tom

This paper discusses social and emotional development during childhood and adolescence in the United States, focusing on factors that affect children's prosocial behavior and the role of parents in promoting such behavior. It is argued that changing family structures, including the growth of single parent families and "latch-key" children, along…

Increases in mean annual temperature do not alter soil bacterial community structure in tropical montane wet forests

Treesearch

Paul C. Selmants; Karen L. Adair; Creighton M. Litton; Christian P. Giardina; Egbert Schwartz

2016-01-01

Soil bacteria play a key role in regulating terrestrial biogeochemical cycling and greenhouse gas fluxes across the soil-atmosphere continuum. Despite their importance to ecosystem functioning, we lack a general understanding of how bacterial communities respond to climate change, especially in relatively understudied ecosystems like tropical montane wet...

University Students' Strategies for Constructing Hypothesis When Tackling Paper-and-Pencil Tasks in Physics

ERIC Educational Resources Information Center

Guisasola, Jenaro; Ceberio, Mikel; Zubimendi, Jose Luis

2006-01-01

The study we present tries to explore how first year engineering students formulate hypotheses in order to construct their own problem solving structure when confronted with problems in physics. Under the constructivistic perspective of the teaching-learning process, the formulation of hypotheses plays a key role in contrasting the coherence of…

Modeling of DNA and Protein Organization Levels with Cn3D Software

ERIC Educational Resources Information Center

Stasinakis, Panagiotis K.; Nicolaou, Despoina

2017-01-01

The molecular structure of living organisms and the complex interactions amongst its components are the basis for the diversity observed at the macroscopic level. Proteins and nucleic acids are some of the major molecular components, and play a key role in several biological functions, such as those of development and evolution. This article…

Meeting Market Demands. New Roles for One-Stop Centers: Serving the Business Customer.

ERIC Educational Resources Information Center

2000

This booklet explains how local communities can organize and structure their one-stop centers so that business is viewed as a customer of the system. The introduction provides an overview of the booklet's development and purpose. The following key attributes underpinning a workforce investment system that views business as its customer are…

Post-Training Unilateral Amygdala Lesions Selectively Impair Contextual Fear Memories

ERIC Educational Resources Information Center

Flavell, Charlotte R.; Lee, Jonathan L. C.

2012-01-01

The basolateral amygdala (BLA) and the dorsal hippocampus (dHPC) are both structures with key roles in contextual fear conditioning. During fear conditioning, it is postulated that contextual representations of the environment are formed in the hippocampus, which are then associated with foot shock in the amygdala. However, it is not known to what…

Extending Basic Learning Opportunities: Challenge and Response. UNESCO-UNICEF Co-operative Programme Digest No. 16.

ERIC Educational Resources Information Center

Prakasha, Veda; And Others

This digest focuses on problems encountered in the expansion of facilities for universal primary education and responses being developed to overcome these problems. The central message of the document is that nonformal structures of learning and community involvement play a key role in the expansion of basic learning opportunities in the…

Does the Document Matter? The Evolving Role of Syllabi in Higher Education

ERIC Educational Resources Information Center

Palmer, Michael S.; Wheeler, Lindsay B.; Aneece, Itiya

2016-01-01

Essentially, the syllabus is a physical artifact outlining key structural elements of a course. It often serves contractual, record keeping, and/or communication functions. It is the place where faculty describe what content they will cover, what books and articles their students will read, the assignments they will complete, dates when things are…

Engagement in Structured Social Space: An Investigation of Teachers' Online Peer-to-Peer Interaction

ERIC Educational Resources Information Center

Robson, James

2016-01-01

With a growing number of teachers engaging online with their peers, online social spaces are increasingly highlighted as playing a key role in teachers' professional learning and development. However, while academic and professional discourses tend to focus on the benefits and weaknesses of teachers' engagement in online social spaces, little…

Dealing with Organizational Silos with Communities of Practice and Human Resource Management

ERIC Educational Resources Information Center

Forsten-Astikainen, Riitta; Hurmelinna-Laukkanen, Pia; Lämsä, Tuija; Heilmann, Pia; Hyrkäs, Elina

2017-01-01

Purpose: Organizational silos that build on the existing organizational structures are often considered to have negative effects in the form of focus on private narrow objectives and organizational fragmentation. To avoid such harmful outcomes, competence management is called for, and in this, the human resources (HR) function takes a key role.…

Job Motivation and Job Satisfaction among Academic Staff in Higher Education

ERIC Educational Resources Information Center

Stankovska, Gordana; Angelkoska, Slagana; Osmani, Fadbi; Grncarovska, Svetlana Pandiloska

2017-01-01

Education is the most important organization of a nation; it plays a significant role in the development of any country. Universities create and cultivate knowledge for the sake of building a modern world. The academic staff is the key resource within higher education institutions. A positive and healthy university structure results in increased…

Examining the Role of Concentration, Vocabulary and Self-Concept in Listening and Reading Comprehension

ERIC Educational Resources Information Center

Wolfgramm, Christine; Suter, Nicole; Göksel, Eva

2016-01-01

Listening is regarded as a key requirement for successful communication and is fundamentally linked to other language skills. Unlike reading, it requires both hearing and processing information in real-time. We therefore propose that the ability to concentrate is a strong predictor of listening comprehension. Using structural equation modeling,…

Evaluation of hypophosphatemia: lessons from patients with genetic disorders

PubMed Central

Bacchetta, Justine; Salusky, Isidro B

2014-01-01

Phosphate is a key element for several physiological pathways, such as skeletal development, bone mineralization, membrane composition, nucleotide structure, maintenance of plasma pH, and cellular signaling. The kidneys have a key role in phosphate homeostasis with three hormones playing important roles in renal phosphate handling (i.e., parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and 1-25 dihydroxy-vitamin D). Independently of the genetic diseases affecting the FGF23 pathway (such as hypophosphatemic rickets), hypophosphatemia is a frequent condition in daily practice, and untreated severe hypophosphatemia can induce hemolysis, rhabdomyolysis, respiratory failure, cardiac dysfunction and neurological impairment, thus requiring a rapid correction to avoid severe complications. The aims of this case report are to summarize the etiologies and the biological evaluation of hypophosphatemia in adults, and to provide an overview of our current understanding of phosphate metabolism. PMID:22075221

The dynamics of male brooding, mating patterns, and sex roles in pipefishes and seahorses (family Syngnathidae).

PubMed

Wilson, Anthony B; Ahnesjö, Ingrid; Vincent, Amanda C J; Meyer, Axel

2003-06-01

Modern theory predicts that relative parental investment of the sexes in their young is a key factor responsible for sexual selection. Seahorses and pipefishes (family Syngnathidae) are extraordinary among fishes in their remarkable adaptations for paternal care and frequent occurrences of sex-role reversals (i.e., female-female competition for mates), offering exceptional opportunities to test predictions of sexual selection theory. During mating, the female transfers eggs into or onto specialized egg-brooding structures that are located on either the male's abdomen or its tail, where they are osmoregulated, aerated, and nourished by specially adapted structures. All syngnathid males exhibit this form of parental care but the brooding structures vary, ranging from the simple ventral gluing areas of some pipefishes to the completely enclosed pouches found in seahorses. We present a molecular phylogeny that indicates that the diversification of pouch types is positively correlated with the major evolutionary radiation of the group, suggesting that this extreme development and diversification of paternal care may have been an important evolutionary innovation of the Syngnathidae. Based on recent studies that show that the complexity of brooding structures reflects the degree of paternal investment in several syngnathid species, we predicted sex-role reversals to be more common among species with more complex brooding structures. In contrast to this prediction, however, both parsimony- and likelihood-based reconstructions of the evolution of sex-role reversal in pipefishes and seahorses suggest multiple shifts in sex roles in the group, independent from the degree of brood pouch development. At the same time, our data demonstrate that sex-role reversal is positively associated with polygamous mating patterns, whereas most nonreversed species mate monogamously, suggesting that selection for polygamy or monogamy in pipefishes and seahorses may strongly influence sex roles in the wild.

A role for the ESCRT system in cell division in archaea.

PubMed

Samson, Rachel Y; Obita, Takayuki; Freund, Stefan M; Williams, Roger L; Bell, Stephen D

2008-12-12

Archaea are prokaryotic organisms that lack endomembrane structures. However, a number of hyperthermophilic members of the Kingdom Crenarchaea, including members of the Sulfolobus genus, encode homologs of the eukaryotic endosomal sorting system components Vps4 and ESCRT-III (endosomal sorting complex required for transport-III). We found that Sulfolobus ESCRT-III and Vps4 homologs underwent regulation of their expression during the cell cycle. The proteins interacted and we established the structural basis of this interaction. Furthermore, these proteins specifically localized to the mid-cell during cell division. Overexpression of a catalytically inactive mutant Vps4 in Sulfolobus resulted in the accumulation of enlarged cells, indicative of failed cell division. Thus, the archaeal ESCRT system plays a key role in cell division.

The stability of DOTA-chelated radiopharmaceuticals within 225Ac decay pathway studied with density functional theory.

NASA Astrophysics Data System (ADS)

Karolak, Aleksandra; Khabibullin, Artem; Budzevich, Mikalai; Martinez, M.; Doliganski, Michael; McLaughlin, Mark; Woods, Lilia; Morse, David

Ligand structures encapsulating metal ions play a central role as contrast agents in Magnetic Resonance Imaging (MRI) or as agents delivering toxic cargo directly to tumor cells in targeted cancer therapy. The structural stability and interaction with solutions of such complexes are the key elements in understanding the foundation of delivery process. We present a comparative study for the 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelated to radioactive isotopes of 225Ac, 221Fr, 217At, 213Bi and a control 68Gd. Using density functional theory methods we investigate the structural stability of complexes for cancer therapy including binding energies, charge transfer, electron densities. The van der Waals interactions are included in the simulations to take into account weak dispersion forces present in such structures. Our results reveal that Ac-DOTA, Bi-DOTA and Gd-DOTA are the most stable complexes in the group. We also show that the water environment is a key ingredient for the structural coordination of the DOTA structures. Support from the US Department of Energy under Grant No. DE-FG02-06ER46297 is acknowledged.

Structural maintenance of chromosome complexes differentially compact mitotic chromosomes according to genomic context

PubMed Central

Schalbetter, S. A.; Goloborodko, A.; Fudenberg, G.; Belton, J.-M.; Miles, C.; Yu, M.; Dekker, J.; Mirny, L.; Baxter, J.

2017-01-01

Structural Maintenance of Chromosomes (SMC) protein complexes are key determinants of chromosome conformation. Using Hi-C and polymer modeling, we study how cohesin and condensin, two deeply conserved SMC complexes, organize chromosomes in the budding yeast Saccharomyces cerevisiae. The canonical role of cohesin is to co-align sister chromatids whilst condensin generally compacts mitotic chromosomes. We find strikingly different roles for the two complexes in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosome arms, independently of sister chromatid cohesion. Polymer simulations demonstrate this role can be fully accounted for through cis-looping of chromatin. Second, condensin is generally dispensable for compaction along chromosome arms. Instead it plays a targeted role compacting the rDNA proximal regions and promoting resolution of peri-centromeric regions. Our results argue that the conserved mechanism of SMC complexes is to form chromatin loops and that distinct SMC-dependent looping activities are selectively deployed to appropriately compact chromosomes. PMID:28825700

Exploring protein interiors: the role of a buried histidine in the KH module fold.

PubMed

Fraternali, F; Amodeo, P; Musco, G; Nilges, M; Pastore, A

1999-03-01

The K-homology (KH) module is a novel RNA-binding motif. The structures of a representative KH motif from vigilin (vig-KH6) and of the first KH domain of fmr1 have been recently solved by nuclear magnetic resonance (NMR) and automated assignment-refinement techniques (ARIA). While a hydrophobic residue is found at position 21 in most of the KH modules, a buried His is conserved in all the 15 KH repeats of vigilin. This position must therefore have a key structural role in stabilizing the hydrophobic core. In the present work, we have addressed the following questions in order to obtain a detailed description of the role of His 21: i) what is the exact role of the histidine in the hydrophobic core of vig-KH6? ii) can we define the interactions that allow a conserved buried position to be occupied by a histidine both in vig-KH6 and in the whole vigilin KH sub-family? iii) how is the structure and stability of vig-KH6 influenced by the state of protonation of this histidine? To answer these questions, we have carried out an extensive refinement of the vig-KH6 structure using both an improved ARIA protocol starting from different initial structures and successively running restrained and unrestrained trajectories in water. An analysis of the stability of secondary structural elements, solvent accessibility, and hydrogen bonding patterns allows hypothesis on the structural role of residue His 21 and on the interactions that this residue forms with the environment. The importance of the protonation state of His 21 on the stability of the KH fold was addressed and validated by experimental results.

Oxygen: A Fundamental Property Regulating Pelagic Ecosystem Structure in the Coastal Southeastern Tropical Pacific

PubMed Central

Bertrand, Arnaud; Chaigneau, Alexis; Peraltilla, Salvador; Ledesma, Jesus; Graco, Michelle; Monetti, Florian; Chavez, Francisco P.

2011-01-01

Background In the southeastern tropical Pacific anchovy (Engraulis ringens) and sardine (Sardinops sagax) abundance have recently fluctuated on multidecadal scales and food and temperature have been proposed as the key parameters explaining these changes. However, ecological and paleoecological studies, and the fact that anchovies and sardines are favored differently in other regions, raise questions about the role of temperature. Here we investigate the role of oxygen in structuring fish populations in the Peruvian upwelling ecosystem that has evolved over anoxic conditions and is one of the world's most productive ecosystems in terms of forage fish. This study is particularly relevant given that the distribution of oxygen in the ocean is changing with uncertain consequences. Methodology/Principal Findings A comprehensive data set is used to show how oxygen concentration and oxycline depth affect the abundance and distribution of pelagic fish. We show that the effects of oxygen on anchovy and sardine are opposite. Anchovy flourishes under relatively low oxygen conditions while sardine avoid periods/areas with low oxygen concentration and restricted habitat. Oxygen consumption, trophic structure and habitat compression play a fundamental role in fish dynamics in this important ecosystem. Conclusions/Significance For the ocean off Peru we suggest that a key process, the need to breathe, has been neglected previously. Inclusion of this missing piece allows the development of a comprehensive conceptual model of pelagic fish populations and change in an ocean ecosystem impacted by low oxygen. Should current trends in oxygen in the ocean continue similar effects may be evident in other coastal upwelling ecosystems. PMID:22216315

Oxygen: a fundamental property regulating pelagic ecosystem structure in the coastal southeastern tropical Pacific.

PubMed

Bertrand, Arnaud; Chaigneau, Alexis; Peraltilla, Salvador; Ledesma, Jesus; Graco, Michelle; Monetti, Florian; Chavez, Francisco P

2011-01-01

In the southeastern tropical Pacific anchovy (Engraulis ringens) and sardine (Sardinops sagax) abundance have recently fluctuated on multidecadal scales and food and temperature have been proposed as the key parameters explaining these changes. However, ecological and paleoecological studies, and the fact that anchovies and sardines are favored differently in other regions, raise questions about the role of temperature. Here we investigate the role of oxygen in structuring fish populations in the Peruvian upwelling ecosystem that has evolved over anoxic conditions and is one of the world's most productive ecosystems in terms of forage fish. This study is particularly relevant given that the distribution of oxygen in the ocean is changing with uncertain consequences. A comprehensive data set is used to show how oxygen concentration and oxycline depth affect the abundance and distribution of pelagic fish. We show that the effects of oxygen on anchovy and sardine are opposite. Anchovy flourishes under relatively low oxygen conditions while sardine avoid periods/areas with low oxygen concentration and restricted habitat. Oxygen consumption, trophic structure and habitat compression play a fundamental role in fish dynamics in this important ecosystem. For the ocean off Peru we suggest that a key process, the need to breathe, has been neglected previously. Inclusion of this missing piece allows the development of a comprehensive conceptual model of pelagic fish populations and change in an ocean ecosystem impacted by low oxygen. Should current trends in oxygen in the ocean continue similar effects may be evident in other coastal upwelling ecosystems. © 2011 Bertrand et al.

Delusions and the Right Hemisphere: A Review of the Case for the Right Hemisphere as a Mediator of Reality-Based Belief.

PubMed

Gurin, Lindsey; Blum, Sonja

2017-01-01

Delusions are beliefs that remain fixed despite evidence that they are incorrect. Although the precise neural mechanism of delusional belief remains to be elucidated, there is a predominance of right-hemisphere lesions among patients with delusional syndromes accompanied by structural pathology, suggesting that right-hemisphere lesions, or networks with key nodes in the right hemisphere, may be playing a role. The authors discuss the potential theoretical basis and empiric support for a specific right-hemisphere role in delusion production, drawing on its roles in pragmatic communication; perceptual integration; attentional surveillance and anomaly/novelty detection; and belief updating.

Sounds of silence: synonymous nucleotides as a key to biological regulation and complexity

PubMed Central

Shabalina, Svetlana A.; Spiridonov, Nikolay A.; Kashina, Anna

2013-01-01

Messenger RNA is a key component of an intricate regulatory network of its own. It accommodates numerous nucleotide signals that overlap protein coding sequences and are responsible for multiple levels of regulation and generation of biological complexity. A wealth of structural and regulatory information, which mRNA carries in addition to the encoded amino acid sequence, raises the question of how these signals and overlapping codes are delineated along non-synonymous and synonymous positions in protein coding regions, especially in eukaryotes. Silent or synonymous codon positions, which do not determine amino acid sequences of the encoded proteins, define mRNA secondary structure and stability and affect the rate of translation, folding and post-translational modifications of nascent polypeptides. The RNA level selection is acting on synonymous sites in both prokaryotes and eukaryotes and is more common than previously thought. Selection pressure on the coding gene regions follows three-nucleotide periodic pattern of nucleotide base-pairing in mRNA, which is imposed by the genetic code. Synonymous positions of the coding regions have a higher level of hybridization potential relative to non-synonymous positions, and are multifunctional in their regulatory and structural roles. Recent experimental evidence and analysis of mRNA structure and interspecies conservation suggest that there is an evolutionary tradeoff between selective pressure acting at the RNA and protein levels. Here we provide a comprehensive overview of the studies that define the role of silent positions in regulating RNA structure and processing that exert downstream effects on proteins and their functions. PMID:23293005

Crystallographic insight into the evolutionary origins of xyloglucan endo-transglycosylases and endo-hydrolases

PubMed Central

McGregor, Nicholas; Yin, Victor; Tung, Ching-Chieh; Van Petegem, Filip; Brumer, Harry

2016-01-01

SUMMARY The xyloglucan endo-transglycosylase/hydrolase (XTH) gene family encodes enzymes of central importance to plant cell wall remodelling. The evolutionary history of plant XTH gene products is incompletely understood vis-à-vis the larger body of bacterial endo-glycanases in Glycoside Hydrolase Family 16 (GH16). To provide molecular insight into this issue, high-resolution X-ray crystal structures and detailed enzyme kinetics of an extant transitional plant endo-glucanase (EG) were determined. Functionally intermediate between plant XTH gene products and bacterial licheninases of GH16, Vitis vinifera EG16 (VvEG16) effectively catalyzes the hydrolysis of the backbones of two dominant plant cell wall matrix glycans, xyloglucan (XyG) and β(1,3)/β(1,4)-mixed-linkage glucan (MLG). Crystallographic complexes with extended oligosaccharide substrates reveal the structural basis for the accommodation of both unbranched, mixed-linked (MLG) and highly decorated, linear (XyG) polysaccharide chains in a broad, extended active-site cleft. Structural comparison with representative bacterial licheninases, a xyloglucan endo-tranglycosylase (XET), and a xyloglucan endo-hydrolase (XEH) outline the functional ramifications of key sequence deletions and insertions across the phylogenetic landscape of GH16. Although the biological role(s) of EG16 orthologs remains to be fully resolved, the present biochemical and tertiary structural characterization provides key insight into plant cell wall enzyme evolution, which will continue to inform genomic analyses and functional studies across species. PMID:27859885

Structural studies of cinnamoyl-CoA reductase and cinnamyl-alcohol dehydrogenase, key enzymes of monolignol biosynthesis.

PubMed

Pan, Haiyun; Zhou, Rui; Louie, Gordon V; Mühlemann, Joëlle K; Bomati, Erin K; Bowman, Marianne E; Dudareva, Natalia; Dixon, Richard A; Noel, Joseph P; Wang, Xiaoqiang

2014-09-01

The enzymes cinnamoyl-CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD) catalyze the two key reduction reactions in the conversion of cinnamic acid derivatives into monolignol building blocks for lignin polymers in plant cell walls. Here, we describe detailed functional and structural analyses of CCRs from Medicago truncatula and Petunia hybrida and of an atypical CAD (CAD2) from M. truncatula. These enzymes are closely related members of the short-chain dehydrogenase/reductase (SDR) superfamily. Our structural studies support a reaction mechanism involving a canonical SDR catalytic triad in both CCR and CAD2 and an important role for an auxiliary cysteine unique to CCR. Site-directed mutants of CAD2 (Phe226Ala and Tyr136Phe) that enlarge the phenolic binding site result in a 4- to 10-fold increase in activity with sinapaldehyde, which in comparison to the smaller coumaraldehyde and coniferaldehyde substrates is disfavored by wild-type CAD2. This finding demonstrates the potential exploitation of rationally engineered forms of CCR and CAD2 for the targeted modification of monolignol composition in transgenic plants. Thermal denaturation measurements and structural comparisons of various liganded and unliganded forms of CCR and CAD2 highlight substantial conformational flexibility of these SDR enzymes, which plays an important role in the establishment of catalytically productive complexes of the enzymes with their NADPH and phenolic substrates. © 2014 American Society of Plant Biologists. All rights reserved.

CarD uses a minor groove wedge mechanism to stabilize the RNA polymerase open promoter complex.

PubMed

Bae, Brian; Chen, James; Davis, Elizabeth; Leon, Katherine; Darst, Seth A; Campbell, Elizabeth A

2015-09-08

A key point to regulate gene expression is at transcription initiation, and activators play a major role. CarD, an essential activator in Mycobacterium tuberculosis, is found in many bacteria, including Thermus species, but absent in Escherichia coli. To delineate the molecular mechanism of CarD, we determined crystal structures of Thermus transcription initiation complexes containing CarD. The structures show CarD interacts with the unique DNA topology presented by the upstream double-stranded/single-stranded DNA junction of the transcription bubble. We confirm that our structures correspond to functional activation complexes, and extend our understanding of the role of a conserved CarD Trp residue that serves as a minor groove wedge, preventing collapse of the transcription bubble to stabilize the transcription initiation complex. Unlike E. coli RNAP, many bacterial RNAPs form unstable promoter complexes, explaining the need for CarD.

Insights Into the Role of Collagen in Vocal Fold Health and Disease.

PubMed

Tang, Sharon S; Mohad, Vidisha; Gowda, Madhu; Thibeault, Susan L

2017-09-01

As one of the key fibrous proteins in the extracellular matrix, collagen plays a significant role in the structural and biomechanical characteristics of the vocal fold. Anchored fibrils of collagen create secure structural regions within the vocal folds and are strong enough to sustain vibratory impact and stretch during phonation. This contributes tensile strength, density, and organization to the vocal folds and influences health and pathogenesis. This review offers a comprehensive summary for a current understanding of collagen within normal vocal fold tissues throughout the life span as well as vocal pathology and wound repair. Further, collagen's molecular structure and biosynthesis are discussed. Finally, collagen alterations in tissue injury and repair and the incorporation of collagen-based biomaterials as a method of treating voice disorders are reviewed. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Structural and Dynamical Details of Biotin

NASA Astrophysics Data System (ADS)

Korter, Timothy; Dunmire, David; Romero, Danilo; Middleton, Chris; Jenkins, Tim; Hudson, Bruce; Hight Walker, Angela

2003-03-01

Biotin, one of the B vitamins, is a key cofactor of enzymes that transfer units of CO2. Chemically linked to a lysine residue via its carboxylic acid side chain, biotin exhibits incredible flexibility when performing its intraprotein transport role. Not only does Biotin play a critical role in gluconeogenesis, it also is commonly used throughout biotechnology research due to its strong binding affinity for attachment, tethering and labeling chemistries. Therefore, a detailed probe of the structure and dynamics of biotin is important both metabolically and to aid further research. Here, we used several vibrational techniques, THz, IR, Raman and Inelastic Neutron Scattering, to gain a comprehensive understanding of biotin's structure, flexibility and dynamics. Specifically our interests are in hydrogen bonding interactions, torsional vibrations, and conformational changes with varying environments, which frequently lie in the far-infrared region of the spectrum below 200 cm-1. Interpretation and comparison of our multi-technique data are guided by high-level ab initio calculations.

GAS PHASE SYNTHESIS OF (ISO)QUINOLINE AND ITS ROLE IN THE FORMATION OF NUCLEOBASES IN THE INTERSTELLAR MEDIUM

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

Parker, Dorian S. N.; Kaiser, Ralf I.; Kostko, Oleg

Nitrogen-substituted polycyclic aromatic hydrocarbons (NPAHs) have been proposed to play a key role in the astrochemical evolution of the interstellar medium, yet the formation mechanisms of even their simplest prototypes—quinoline and isoquinoline—remain elusive. Here, we reveal a novel concept that under high temperature conditions representing circumstellar envelopes of carbon stars, (iso)quinoline can be synthesized via the reaction of pyridyl radicals with two acetylene molecules. The facile gas phase formation of (iso)quinoline in circumstellar envelopes defines a hitherto elusive reaction class synthesizing aromatic structures with embedded nitrogen atoms that are essential building blocks in contemporary biological-structural motifs. Once ejected from circumstellarmore » shells and incorporated into icy interstellar grains in cold molecular clouds, these NPAHs can be functionalized by photo processing forming nucleobase-type structures as sampled in the Murchison meteorite.« less

Movement dynamics reflect a functional role for weak coupling and role structure in dyadic problem solving.

PubMed

Abney, Drew H; Paxton, Alexandra; Dale, Rick; Kello, Christopher T

2015-11-01

Successful interaction requires complex coordination of body movements. Previous research has suggested a functional role for coordination and especially synchronization (i.e., time-locked movement across individuals) in different types of human interaction contexts. Although such coordination has been shown to be nearly ubiquitous in human interaction, less is known about its function. One proposal is that synchrony supports and facilitates communication (Topics Cogn Sci 1:305-319, 2009). However, questions still remain about what the properties of coordination for optimizing communication might look like. In the present study, dyads worked together to construct towers from uncooked spaghetti and marshmallows. Using cross-recurrence quantification analysis, we found that dyads with loosely coupled gross body movements performed better, supporting recent work suggesting that simple synchrony may not be the key to effective performance (Riley et al. 2011). We also found evidence that leader-follower dynamics-when sensitive to the specific role structure of the interaction-impact task performance. We discuss our results with respect to the functional role of coordination in human interaction.

Bacterial morphogenesis and the enigmatic MreB helix.

PubMed

Errington, Jeff

2015-04-01

Work over the past decade has highlighted the pivotal role of the actin-like MreB family of proteins in the determination and maintenance of rod cell shape in bacteria. Early images of MreB localization revealed long helical filaments, which were suggestive of a direct role in governing cell wall architecture. However, several more recent, higher-resolution studies have questioned the existence or importance of the helical structures. In this Opinion article, I navigate a path through these conflicting reports, revive the helix model and summarize the key questions that remain to be answered.

GaN-based LEDs with a high light extraction composite surface structure fabricated by a modified YAG laser lift-off technology and the patterned sapphire substrates

NASA Astrophysics Data System (ADS)

Sun, Yongjian; Trieu, Simeon; Yu, Tongjun; Chen, Zhizhong; Qi, Shengli; Tian, Pengfei; Deng, Junjing; Jin, Xiaoming; Zhang, Guoyi

2011-08-01

Vertical structure LEDs have been fabricated with a novel light extraction composite surface structure composed of a micron grating and nano-structure. The composite surface structure was generated by using a modified YAG laser lift-off technique, separating the wafers from cone-shaped patterned sapphire substrates. LEDs thus fabricated showed the light output power increase about 1.7-2.5 times when compared with conventional vertical structure LEDs grown on plane sapphire substrates. A three-dimensional finite difference time domain method was used to simulate this new kind of LED device. It was determined that nano-structures in composite surface patterns play a key role in the improvement of light extraction efficiency of LEDs.

The personal value of being a palliative care Community Volunteer Worker in Uganda: a qualitative study.

PubMed

Jack, Barbara A; Kirton, Jennifer A; Birakurataki, Jerith; Merriman, Anne

2012-07-01

Volunteers in palliative care play a key role, particularly in the hospice setting. The expansion of palliative care into developing countries has been accompanied by the emergence of volunteer workers, who are providing a main source of support and care for patients, many of whom never see a health professional. The aim of this study was to evaluate the motivation for becoming a volunteer and the personal impact of being a palliative care Community Volunteer Worker in Uganda. A qualitative methodology using semi-structured individual and group digitally recorded interviews was adopted for the study. Data were analysed for emerging themes using thematic analysis. Forty-three interviews were undertaken, 32 with Community Volunteer Workers and 11 with the Hospice clinical teams, using semi-structured digitally recorded individual, group and focus group interviews at the Hospice Africa sites in Uganda. The results identified the cultural wish to help people as a key motivator in becoming a volunteer. Additionally, the volunteers reported having a sense of pride in their volunteering role, and this role had a positive impact on their perceived status in their local community. This model of volunteering is clearly having an impact on the volunteers, both personally and also in terms of how they are treated in their communities. Further research to explore the long-term personal benefits of being a palliative care volunteer is recommended.

Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease

PubMed Central

2016-01-01

Airway structure and function are key aspects of normal lung development, growth, and aging, as well as of lung responses to the environment and the pathophysiology of important diseases such as asthma, chronic obstructive pulmonary disease, and fibrosis. In this regard, the contributions of airway smooth muscle (ASM) are both functional, in the context of airway contractility and relaxation, as well as synthetic, involving production and modulation of extracellular components, modulation of the local immune environment, cellular contribution to airway structure, and, finally, interactions with other airway cell types such as epithelium, fibroblasts, and nerves. These ASM contributions are now found to be critical in airway hyperresponsiveness and remodeling that occur in lung diseases. This review emphasizes established and recent discoveries that underline the central role of ASM and sets the stage for future research toward understanding how ASM plays a central role by being both upstream and downstream in the many interactive processes that determine airway structure and function in health and disease. PMID:27742732

Structural Insights on the Mycobacterium tuberculosis Proteasomal ATPase Mpa

PubMed Central

Wang, Tao; Li, Hua; Lin, Gang; Tang, Chunyan; Li, Dongyang; Nathan, Carl; Darwin, K. Heran; Li, Huilin

2009-01-01

Summary Proteasome-mediated protein turnover in all domains of life is an energy-dependent process that requires ATPase activity. Mycobacterium tuberculosis (Mtb) was recently shown to possess a ubiquitin-like proteasome pathway that plays an essential role in Mtb resistance to killing by products of host macrophages. Here we report our structural and biochemical investigation of Mpa, the presumptive Mtb proteasomal ATPase. We demonstrate that Mpa binds to the Mtb proteasome in the presence of ATPγS, providing the physical evidence that Mpa is the proteasomal ATPase. X-ray crystallographic determination of the conserved inter-domain showed a five-stranded double β-barrel structure containing a Greek key motif. The structure and mutagenesis indicate a major role of the inter-domain for Mpa hexamerization. Our mutational and functional studies further suggest that the central channel in the Mpa hexamer is involved in protein substrate translocation and degradation. These studies provide insights into how a bacterial proteasomal ATPase interacts with and facilitates protein degradation by the proteasome. PMID:19836337

Science in Emergency Response at CDC: Structure and Functions.

PubMed

Iskander, John; Rose, Dale A; Ghiya, Neelam D

2017-09-01

Recent high-profile activations of the US Centers for Disease Control and Prevention (CDC) Emergency Operations Center (EOC) include responses to the West African Ebola and Zika virus epidemics. Within the EOC, emergency responses are organized according to the Incident Management System, which provides a standardized structure and chain of command, regardless of whether the EOC activation occurs in response to an outbreak, natural disaster, or other type of public health emergency. By embedding key scientific roles, such as the associate director for science, and functions within a Scientific Response Section, the current CDC emergency response structure ensures that both urgent and important science issues receive needed attention. Key functions during emergency responses include internal coordination of scientific work, data management, information dissemination, and scientific publication. We describe a case example involving the ongoing Zika virus response that demonstrates how the scientific response structure can be used to rapidly produce high-quality science needed to answer urgent public health questions and guide policy. Within the context of emergency response, longer-term priorities at CDC include both streamlining administrative requirements and funding mechanisms for scientific research.

Key experimental information on intermediate-range atomic structures in amorphous Ge2Sb2Te5 phase change material

NASA Astrophysics Data System (ADS)

Hosokawa, Shinya; Pilgrim, Wolf-Christian; Höhle, Astrid; Szubrin, Daniel; Boudet, Nathalie; Bérar, Jean-François; Maruyama, Kenji

2012-04-01

Laser-induced crystalline-amorphous phase change of Ge-Sb-Te alloys is the key mechanism enabling the fast and stable writing/erasing processes in rewritable optical storage devices, such as digital versatile disk (DVD) or blu-ray disk. Although the structural information in the amorphous phase is essential for clarifying this fast process, as well as long lasting stabilities of both the phases, experimental works were mostly limited to the short-range order by x ray absorption fine structure. Here we show both the short and intermediate-range atomic structures of amorphous DVD material, Ge2Sb2Te5 (GST), investigated by a combination of anomalous x ray scattering and reverse Monte Carlo modeling. From the obtained atomic configurations of amorphous GST, we have found that the Sb atoms and half of the Ge atoms play roles in the fast phase change process of order-disorder transition, while the remaining Ge atoms act for the proper activation energy of barriers between the amorphous and crystalline phases.

Durability of polymer matrix composites for automotive structural applications: A state-of-the-art review

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

Corum, J.M.; Simpson, W.A. Jr.; Sun, C.T.

1995-07-01

A key unanswered question that must be addressed before polymeric composites will be widely used in automotive structural components is their known durability. Major durability issues are the effects that cyclic loadings, creep, automotive fluid environments, and low-energy impacts have on dimensional stability, strength, and stiffness throughout the required life of a composite component. This report reviews the current state of understanding in each of these areas. It also discusses the limited information that exists on one of the prime candidate materials for automotive structural applications--an isocyanurate reinforced with a continuous strand, swirl mat. Because of the key role thatmore » nondestructive evaluations must play in understanding damage development and progression, a chapter is included on ultrasonic techniques. A final chapter then gives conclusions and recommendations for research needed to resolve the various durability issues. These recommendations will help provide a sound basis for program planning for the Durability of Lightweight Composite Structures Project sponsored by the US Department of Energy in cooperation with the Automotive Composites Consortium of Chrysler, Ford, and General Motors.« less

The Structure of the Human Centrin 2-Xeroderma Pigmentosum Group C Protein Complex

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

Thompson,J.; Ryan, Z.; Salisbury, J.

2006-01-01

Human centrin-2 plays a key role in centrosome function and stimulates nucleotide excision repair by binding to the xeroderma pigmentosum group C protein. To determine the structure of human centrin-2 and to develop an understanding of molecular interactions between centrin and xeroderma pigmentosum group C protein, we characterized the crystal structure of calcium-loaded full-length centrin-2 complexed with a xeroderma pigmentosum group C peptide. Our structure shows that the carboxyl-terminal domain of centrin-2 binds this peptide and two calcium atoms, whereas the amino-terminal lobe is in a closed conformation positioned distantly by an ordered {alpha}-helical linker. A stretch of the amino-terminalmore » domain unique to centrins appears disordered. Two xeroderma pigmentosum group C peptides both bound to centrin-2 also interact to form an {alpha}-helical coiled-coil. The interface between centrin-2 and each peptide is predominantly nonpolar, and key hydrophobic residues of XPC have been identified that lead us to propose a novel binding motif for centrin.« less

Increased Diversity of Libraries from Libraries: Chemoinformatic Analysis of Bis-Diazacyclic Libraries

PubMed Central

López-Vallejo, Fabian; Nefzi, Adel; Bender, Andreas; Owen, John R.; Nabney, Ian T.; Houghten, Richard A.; Medina-Franco, Jose L.

2011-01-01

Combinatorial libraries continue to play a key role in drug discovery. To increase structural diversity, several experimental methods have been developed. However, limited efforts have been performed so far to quantify the diversity of the broadly used diversity-oriented synthetic (DOS) libraries. Herein we report a comprehensive characterization of 15 bis-diazacyclic combinatorial libraries obtained through libraries from libraries, which is a DOS approach. Using MACCS keys, radial and different pharmacophoric fingerprints as well as six molecular properties, it was demonstrated the increased structural and property diversity of the libraries from libraries over the individual libraries. Comparison of the libraries to existing drugs, NCI Diversity and the Molecular Libraries Small Molecule Repository revealed the structural uniqueness of the combinatorial libraries (mean similarity < 0.5 for any fingerprint representation). In particular, bis-cyclic thiourea libraries were the most structurally dissimilar to drugs retaining drug-like character in property space. This study represents the first comprehensive quantification of the diversity of libraries from libraries providing a solid quantitative approach to compare and contrast the diversity of DOS libraries with existing drugs or any other compound collection. PMID:21294850

Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL.

PubMed

Della Gatta, Giusy; Palomero, Teresa; Perez-Garcia, Arianne; Ambesi-Impiombato, Alberto; Bansal, Mukesh; Carpenter, Zachary W; De Keersmaecker, Kim; Sole, Xavier; Xu, Luyao; Paietta, Elisabeth; Racevskis, Janis; Wiernik, Peter H; Rowe, Jacob M; Meijerink, Jules P; Califano, Andrea; Ferrando, Adolfo A

2012-02-26

The TLX1 and TLX3 transcription factor oncogenes have a key role in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). Here we used reverse engineering of global transcriptional networks to decipher the oncogenic regulatory circuit controlled by TLX1 and TLX3. This systems biology analysis defined T cell leukemia homeobox 1 (TLX1) and TLX3 as master regulators of an oncogenic transcriptional circuit governing T-ALL. Notably, a network structure analysis of this hierarchical network identified RUNX1 as a key mediator of the T-ALL induced by TLX1 and TLX3 and predicted a tumor-suppressor role for RUNX1 in T cell transformation. Consistent with these results, we identified recurrent somatic loss-of-function mutations in RUNX1 in human T-ALL. Overall, these results place TLX1 and TLX3 at the top of an oncogenic transcriptional network controlling leukemia development, show the power of network analyses to identify key elements in the regulatory circuits governing human cancer and identify RUNX1 as a tumor-suppressor gene in T-ALL.

Structural Landscape of the Proline-Rich Domain of Sos1 Nucleotide Exchange Factor

PubMed Central

McDonald, Caleb B.; Bhat, Vikas; Kurouski, Dmitry; Mikles, David C.; Deegan, Brian J.; Seldeen, Kenneth L.; Lednev, Igor K.; Farooq, Amjad

2013-01-01

Despite its key role in mediating a plethora of cellular signaling cascades pertinent to health and disease, little is known about the structural landscape of the proline-rich (PR) domain of Sos1 guanine nucleotide exchange factor. Herein, using a battery of biophysical tools, we provide evidence that the PR domain of Sos1 is structurally disordered and adopts an extended random coil-like conformation in solution. Of particular interest is the observation that while chemical denaturation of PR domain results in the formation of a significant amount of polyproline II (PPII) helices, it has little or negligible effect on its overall size as measured by its hydrodynamic radius. Our data also show that the PR domain displays a highly dynamic conformational basin in agreement with the knowledge that the intrinsically unstructured proteins rapidly interconvert between an ensemble of conformations. Collectively, our study provides new insights into the conformational equilibrium of a key signaling molecule with important consequences on its physiological function. PMID:23528987

What determines the spectrum of protein native state structures?

PubMed

Lezon, Timothy R; Banavar, Jayanth R; Lesk, Arthur M; Maritan, Amos

2006-05-01

We present a brief summary of the key factors underlying protein structure, as developed in the investigations of Pauling, Ramachandran, and Rose. We then outline a simplified physical model of proteins that focuses on geometry and symmetry. Although this model superficially appears unrelated to the detailed chemical descriptions commonly applied to proteins, we show that it captures the essential elements of the chemistry and provides a unified framework for understanding the common characteristics of folded proteins. We suggest that the spectrum of protein native state structures is determined by geometry and symmetry and the role of the sequence is to choose its native state structure from this predetermined menu. 2006 Wiley-Liss, Inc.

Factors of Problem-Solving Competency in a Virtual Chemistry Environment: The Role of Metacognitive Knowledge about Strategies

ERIC Educational Resources Information Center

Scherer, Ronny; Tiemann, Rudiger

2012-01-01

The ability to solve complex scientific problems is regarded as one of the key competencies in science education. Until now, research on problem solving focused on the relationship between analytical and complex problem solving, but rarely took into account the structure of problem-solving processes and metacognitive aspects. This paper,…

Tansley Review No. 104, Calcium Physiology and Terrestrial Ecosystem Processes

Treesearch

S.B. McLaughlin; R. Wimmer

1999-01-01

Calcium occupies a unique position among plant nutrients both chemically and functionally. Its chemical properties allow it to exist in a wide range of binding states and to serve in both structural and messenger roles. Despite its importance in many plant processes, Ca mobility is low, making Ca uptake and distribution rate a limiting process for many key plant...

Identification and characterization of matrix metalloproteinase-13 sequence structure and expression during embryogenesis and infection in channel catfish (Ictalurus punctatus)

USDA-ARS?s Scientific Manuscript database

Matrix metalloproteinase-13 (MMP-13), referred to as collagenase-3, is a proteolytic enzyme that plays a key role in degradation and remodelling of host extracellularmatrix proteins. The objective of this study was to characterize the MMP-13 gene in channel catfish, and to determine its pattern of e...

Person-Centred Reviews as a Mechanism for Planning the Post-School Transition of Young People with Intellectual Disability

ERIC Educational Resources Information Center

Kaehne, A.; Beyer, S.

2014-01-01

Background: Person-centred planning has played a key role in the transformation of intellectual disabilities services for more than a decade. The literature has identified clear advantages for service users when service delivery is planned around the individual rather than the user is made to fit into service structures. Researchers however have…

Politics and Education Policy into Practice: Conversations with Former Secretaries of State

ERIC Educational Resources Information Center

Abbott, Ian

2015-01-01

Set against a period of rapid change, education has grown in political importance and policy development has moved from the local authority to central government with a key role being played by the Secretary of State. Based on a series of semi-structured interviews, with 10 politicians who have served as Secretary of State for Education, this…

Schooling Novice Mathematics Teachers on Structures and Strategies: A Bourdieuian Perspective on the Role of "Others" in Classroom Practices

ERIC Educational Resources Information Center

Nolan, Kathleen T.

2016-01-01

School discursive practices produce and reproduce acceptable notions of the good mathematics teacher, thereby shaping identity and agency in becoming a teacher. In this paper, I draw on key aspects of Bourdieu's social field theory--his conceptual "thinking tools" and his reflexive sociology--to explore the relations and discourses of…

School-to-Work Transitions in the OECD: Do Education Systems Make a Difference?

ERIC Educational Resources Information Center

Karmel, Tom

2017-01-01

High unemployment among the young is a concern in many OECD countries. A key issue for policy makers is whether the education system has a role to play in assisting the transition from education to work or whether economic issues dominate. This paper uses OECD country-level data to see whether the structure of countries' education systems,…

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.

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.

Making Sense of the Yeast Sphingolipid Pathway.

PubMed

Megyeri, Márton; Riezman, Howard; Schuldiner, Maya; Futerman, Anthony H

2016-12-04

Sphingolipids (SL) and their metabolites play key roles both as structural components of membranes and as signaling molecules. Many of the key enzymes and regulators of SL metabolism were discovered using the yeast Saccharomyces cerevisiae, and based on the high degree of conservation, a number of mammalian homologs were identified. Although yeast continues to be an important tool for SL research, the complexity of SL structure and nomenclature often hampers the ability of new researchers to grasp the subtleties of yeast SL biology and discover new modulators of this intricate pathway. Moreover, the emergence of lipidomics by mass spectrometry has enabled the rapid identification of SL species in yeast and rendered the analysis of SL composition under various physiological and pathophysiological conditions readily amenable. However, the complex nomenclature of the identified species renders much of the data inaccessible to non-specialists. In this review, we focus on parsing both the classical SL nomenclature and the nomenclature normally used during mass spectrometry analysis, which should facilitate the understanding of yeast SL data and might shed light on biological processes in which SLs are involved. Finally, we discuss a number of putative roles of various yeast SL species. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hairpin Folding of HIV gp41 Abrogates Lipid Mixing Function at Physiologic pH and Inhibits Lipid Mixing by Exposed gp41 Constructs†

PubMed Central

Sackett, Kelly; Nethercott, Matthew J.; Shai, Yechiel; Weliky, David P.

2009-01-01

Conformational changes in the HIV gp41 protein are directly correlated with fusion between the HIV and target cell plasma membranes which is the initial step of infection. Key gp41 fusion conformations include an early extended conformation termed pre-hairpin which contains exposed regions and a final low energy conformation termed hairpin which has compact six-helix bundle structure. Current fusion models debate the roles of hairpin and pre-hairpin conformations in the process of membrane merger. In the present work, gp41 constructs have been engineered which correspond to fusion relevant parts of both pre-hairpin and hairpin conformations, and have been analyzed for their ability to induce lipid mixing between membrane vesicles. The data correlate membrane fusion function with the pre-hairpin conformation and suggest that one of the roles of the final hairpin conformation is sequestration of membrane perturbing gp41 regions with consequent loss of the membrane disruption induced earlier by the pre-hairpin structure. To our knowledge, this is the first biophysical study to delineate the membrane fusion potential of gp41 constructs modeling key fusion conformations. PMID:19222185

Women in senior post-graduate medicine career roles in the UK: a qualitative study.

PubMed

Curtis, Anthony; Eley, Lizzie; Gray, Selena; Irish, Bill

2016-01-01

This qualitative study sought to elicit the views, experiences, career journeys and aspirations of women in senior post-graduate medical education roles to identify steps needed to help support career progression. In-depth semi-structured telephone interviews. UK. Purposive sample of 12 women in a variety of senior leadership roles in post-graduate medical education in the UK. Self reported motivating influences, factors that helped and hindered progress, key branch points, and key educational factors and social support impacting on participants' career in postgraduate medicine. Respondents often reported that career journeys were serendipitous, rather than planned, formal or well structured. Senior women leaders reported having a high internal locus of control, with very high levels of commitment to the NHS. All reported significant levels of drive, although the majority indicated that they were not ambitious in the sense of a strong drive for money, prestige, recognition or power. They perceived that there was an under-representation of women in senior leadership positions and that high-quality female mentorship was particularly important in redressing this imbalance. Social support, such a spouse or other significant family member, was particularly valued as reaffirming and supporting women's chosen career ambition. Factors that were considered to have hindered career progression included low self-confidence and self-efficacy, the so-called glass ceiling and perceived self-limiting cultural influences. Factors indirectly linked to gender such as part-time versus working full time were reportedly influential in being overlooked for senior leadership roles. Implications of these findings are discussed in the paper. Social support, mentorship and role modelling are all perceived as highly important in redressing perceived gender imbalances in careers in post-graduate medical education.

Women in senior post-graduate medicine career roles in the UK: a qualitative study

PubMed Central

Curtis, Anthony; Eley, Lizzie; Irish, Bill

2016-01-01

Objectives This qualitative study sought to elicit the views, experiences, career journeys and aspirations of women in senior post-graduate medical education roles to identify steps needed to help support career progression. Design In-depth semi-structured telephone interviews. Setting UK. Participants Purposive sample of 12 women in a variety of senior leadership roles in post-graduate medical education in the UK. Main outcome measures Self reported motivating influences, factors that helped and hindered progress, key branch points, and key educational factors and social support impacting on participants' career in postgraduate medicine. Results Respondents often reported that career journeys were serendipitous, rather than planned, formal or well structured. Senior women leaders reported having a high internal locus of control, with very high levels of commitment to the NHS. All reported significant levels of drive, although the majority indicated that they were not ambitious in the sense of a strong drive for money, prestige, recognition or power. They perceived that there was an under-representation of women in senior leadership positions and that high-quality female mentorship was particularly important in redressing this imbalance. Social support, such a spouse or other significant family member, was particularly valued as reaffirming and supporting women’s chosen career ambition. Factors that were considered to have hindered career progression included low self-confidence and self-efficacy, the so-called glass ceiling and perceived self-limiting cultural influences. Factors indirectly linked to gender such as part-time versus working full time were reportedly influential in being overlooked for senior leadership roles. Implications of these findings are discussed in the paper. Conclusion Social support, mentorship and role modelling are all perceived as highly important in redressing perceived gender imbalances in careers in post-graduate medical education. PMID:28203382

Structural analysis of the Quaking homodimerization interface

PubMed Central

Beuck, Christine; Qu, Song; Fagg, W. Samuel; Ares, Manuel; Williamson, James R.

2012-01-01

Quaking is a prototypical member of the STAR protein family, which plays key roles in posttranscriptional gene regulation by controlling mRNA translation, stability and splicing. QkI-5 has been shown to regulate mRNA expression in the central nervous system, but little is known about its roles in other tissues. STAR proteins function as dimers and bind to bipartite RNA sequences, however, the structural and functional roles of homo- and hetero-dimerization are still unclear. Here, we present the crystal structure of the QkI dimerization domain, which adopts a similar stacked helix-turn-helix arrangement as its homologs GLD-1 and Sam68, but differs by an additional helix inserted in the dimer interface. Variability of the dimer interface residues likely ensures selective homodimerization by preventing association with non-cognate STAR family proteins in the cell. Mutations that inhibit dimerization also significantly impair RNA binding in vitro, alter QkI-5 protein levels, and impair QkI function in a splicing assay in vivo. Together our results indicate that a functional Qua1 homodimerization domain is required for QkI-5 function in mammalian cells. PMID:22982292

Hydrolase treatments help unravel the function of intervessel pits in xylem hydraulics.

PubMed

Dusotoit-Coucaud, Anaïs; Brunel, Nicole; Tixier, Aude; Cochard, Hervé; Herbette, Stéphane

2014-03-01

Intervessel pits are structures that play a key role in the efficiency and safety functions of xylem hydraulics. However, little is known about the components of the pit membrane (PM) and their role in hydraulic functions, especially in resistance to cavitation. We tested the effect of commercial chemicals including a cellulase, a hemicellulase, a pectolyase, a proteinase and DTT on xylem hydraulic properties: vulnerability to cavitation (VC) and conductance. The effects were tested on branch segments from Fagus sylvatica (where the effects on pit structure were analyzed using TEM) and Populus tremula. Cellulose hydrolysis resulted in a sharp increase in VC and a significant increase in conductance, related to complete breakdown of the PM. Pectin hydrolysis also induced a sharp increase in VC but with no effect on conductance or pit structure observable by TEM. The other treatments with hemicellulase, proteinase or DTT showed no effect. This study brings evidence that cellulose and pectins are critical components underpinning VC, and that PM components may play distinct roles in the xylem hydraulic safety and efficiency. © 2013 Scandinavian Plant Physiology Society.

Informing radiography curriculum development: The views of UK radiology service managers concerning the 'fitness for purpose' of recent diagnostic radiography graduates.

PubMed

Sloane, C; Miller, P K

2017-09-01

Recent years have seen significant changes in the way medical imaging services are delivered, rapid changes in technology and big increases in the number and ranges of examinations undertaken. Given these changes the study aimed to critically evaluate the fitness for purpose of newly qualified diagnostic radiography. The study employed a grounded theory approach to analyse the interviews of 20 radiology managers from a range of medical imaging providers across the UK. Four key themes emerged from the analysis. These were: curriculum content and structure review; diversification in the role of the radiographer; professionalism and coping and the reformation of career structures. The results indicate the role of the radiographer is now in a state of flux and challenge radiology managers and educators to design curricula and career structures which are better matched the role of the radiographer in the very rapidly changing technological, organisational and social contexts of modern society. Copyright © 2017 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.

Thermodynamic and structure-property study of liquid-vapor equilibrium for aroma compounds.

PubMed

Tromelin, Anne; Andriot, Isabelle; Kopjar, Mirela; Guichard, Elisabeth

2010-04-14

Thermodynamic parameters (T, DeltaH degrees , DeltaS degrees , K) were collected from the literature and/or calculated for five esters, four ketones, two aldehydes, and three alcohols, pure compounds and compounds in aqueous solution. Examination of correlations between these parameters and the range values of DeltaH degrees and DeltaS degrees puts forward the key roles of enthalpy for vaporization of pure compounds and of entropy in liquid-vapor equilibrium of compounds in aqueous solution. A structure-property relationship (SPR) study was performed using molecular descriptors on aroma compounds to better understand their vaporization behavior. In addition to the role of polarity for vapor-liquid equilibrium of compounds in aqueous solution, the structure-property study points out the role of chain length and branching, illustrated by the correlation between the connectivity index CHI-V-1 and the difference between T and log K for vaporization of pure compounds and compounds in aqueous solution. Moreover, examination of the esters' enthalpy values allowed a probable conformation adopted by ethyl octanoate in aqueous solution to be proposed.

Role of Hypoxia-Induced Brain Derived Neurotrophic Factor in Human Pulmonary Artery Smooth Muscle

PubMed Central

Hartman, William; Helan, Martin; Smelter, Dan; Sathish, Venkatachalem; Thompson, Michael; Pabelick, Christina M.; Johnson, Bruce; Prakash, Y. S.

2015-01-01

Background Hypoxia effects on pulmonary artery structure and function are key to diseases such as pulmonary hypertension. Recent studies suggest that growth factors called neurotrophins, particularly brain-derived neurotrophic factor (BDNF), can influence lung structure and function, and their role in the pulmonary artery warrants further investigation. In this study, we examined the effect of hypoxia on BDNF in humans, and the influence of hypoxia-enhanced BDNF expression and signaling in human pulmonary artery smooth muscle cells (PASMCs). Methods and Results 48h of 1% hypoxia enhanced BDNF and TrkB expression, as well as release of BDNF. In arteries of patients with pulmonary hypertension, BDNF expression and release was higher at baseline. In isolated PASMCs, hypoxia-induced BDNF increased intracellular Ca2+ responses to serotonin: an effect altered by HIF1α inhibition or by neutralization of extracellular BDNF via chimeric TrkB-Fc. Enhanced BDNF/TrkB signaling increased PASMC survival and proliferation, and decreased apoptosis following hypoxia. Conclusions Enhanced expression and signaling of the BDNF-TrkB system in PASMCs is a potential mechanism by which hypoxia can promote changes in pulmonary artery structure and function. Accordingly, the BDNF-TrkB system could be a key player in the pathogenesis of hypoxia-induced pulmonary vascular diseases, and thus a potential target for therapy. PMID:26192455

Bacterial cellulose biosynthesis: diversity of operons, subunits, products and functions

PubMed Central

Römling, Ute; Galperin, Michael Y.

2015-01-01

Summary Recent studies of bacterial cellulose biosynthesis, including structural characterization of a functional cellulose synthase complex, provided the first mechanistic insight into this fascinating process. In most studied bacteria, just two subunits, BcsA and BcsB, are necessary and sufficient for the formation of the polysaccharide chain in vitro. Other subunits – which differ among various taxa – affect the enzymatic activity and product yield in vivo by modulating expression of biosynthesis apparatus, export of the nascent β-D-glucan polymer to the cell surface, and the organization of cellulose fibers into a higher-order structure. These auxiliary subunits play key roles in determining the quantity and structure of the resulting biofilm, which is particularly important for interactions of bacteria with higher organisms that lead to rhizosphere colonization and modulate virulence of cellulose-producing bacterial pathogens inside and outside of host cells. Here we review the organization of four principal types of cellulose synthase operons found in various bacterial genomes, identify additional bcs genes that encode likely components of the cellulose biosynthesis and secretion machinery, and propose a unified nomenclature for these genes and subunits. We also discuss the role of cellulose as a key component of biofilms formed by a variety of free-living and pathogenic bacteria and, for the latter, in the choice between acute infection and persistence in the host. PMID:26077867

Gene analysis and structure prediction for the cold-adaption mechanism of trypsin from the krill Euphausia superba (Dana, 1852).

PubMed

Zhou, Tingting; Wang, Xichang; Yan, Juan; Li, Yan

2018-06-01

The ability of Antarctic krill, Euphausia superba (Dana, 1852), to thrive in a cold environment comes from its capacity to synthesize cold-adapted enzymes. Its trypsin, as a main substance in the metabolic reactions, plays a key role in the adaption to low temperatures. However, the progress of research on its cold-adaption mechanism is being influenced due to the limited information on its gene and spatial structure. We studied the gene of E. superba trypsin with transcriptome sequencing first, and then discussed its cold-adaption mechanism with the full gene and predicted structure basing on bioinformatics. The results showed the proportion of certain residues played important roles in the cold-adaptation behavior for trypsin. Furthermore, a higher proportion of random coils and reduced steric hindrance might also be key factors promoting its cold adaption. This research aimed to reveal the cold-adaption mechanism of E. superba trypsin and provide support for basic research on molecular modification by site-directed mutagenesis of complementary DNA used to produce new and improved recombinant variants with cold adaption. Furthermore, it may broaden its commercial application on minimizing undesirable changes elevated at higher temperature in food processing and in treatment of trauma and inflammation in medicine. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

The role of the general practitioner in multidisciplinary teams: a qualitative study in elderly care.

PubMed

Grol, Sietske M; Molleman, Gerard R M; Kuijpers, Anne; van der Sande, Rob; Fransen, Gerdine A J; Assendelft, Willem J J; Schers, Henk J

2018-03-10

In the western world, a growing number of the older people live at home. In the Netherlands, GPs are expected to play a pivotal role in the organization of integrated care for this patient group. However, little is known about how GPs can play this role best. Our aim for this study was to unravel how GPs can play a successful role in elderly care, in particular in multidisciplinary teams, and to define key concepts for success. A mixed qualitative research model in four multidisciplinary teams for elderly care in the Netherlands was used. With these four teams, consisting of 46 health care and social service professionals, we carried out two rounds of focus-group interviews. Moreover, we performed semi-structured interviews with four GPs. We analysed data using a hybrid inductive/deductive thematic analysis. According to the health care and social service professionals in our study, the role of GPs in multidisciplinary teams for elderly care was characterized by the ability to 'see the bigger picture'. We identified five key activities that constitute a successful GP role: networking, facilitating, team building, integrating care elements, and showing leadership. Practice setting and phase of multidisciplinary team development influenced the way in which GPs fulfilled their roles. According to team members, GPs were the central professionals in care services for older people. The opinions of GPs about their own roles were diverse. GPs took an important role in successful care settings for older people. Five key concepts seemed to be important for best practices in care for frail older people: networking (community), facilitating (organization), team building (professional), integrating care elements (patient), and leadership (personal). Team members from primary care and social services indicated that GPs had an indispensable role in such teams. It would be advantageous for GPs to be aware of this attributed role. Attention to leadership competencies and to the diversity of roles in multidisciplinary teams in GP training programmes seems useful. The challenge is to convince GPs to take a lead, also when they are not inclined to take this role in organizing multidisciplinary teams for older people.

Medical Student Self-Efficacy with Family-Centered Care during Bedside Rounds

PubMed Central

Young, Henry N.; Schumacher, Jayna B.; Moreno, Megan A.; Brown, Roger L.; Sigrest, Ted D.; McIntosh, Gwen K.; Schumacher, Daniel J.; Kelly, Michelle M.; Cox, Elizabeth D.

2012-01-01

Purpose Factors that support self-efficacy must be understood in order to foster family-centered care (FCC) during rounds. Based on social cognitive theory, this study examined (1) how 3 supportive experiences (observing role models, having mastery experiences, and receiving feedback) influence self-efficacy with FCC during rounds and (2) whether the influence of these supportive experiences was mediated by self-efficacy with 3 key FCC tasks (relationship building, exchanging information, and decision making). Method Researchers surveyed 184 students during pediatric clerkship rotations during the 2008–2011 academic years. Surveys assessed supportive experiences and students’ self-efficacy with FCC during rounds and with key FCC tasks. Measurement models were constructed via exploratory and confirmatory factor analyses. Composite indicator structural equation (CISE) models evaluated whether supportive experiences influenced self-efficacy with FCC during rounds and whether self-efficacy with key FCC tasks mediated any such influences. Results Researchers obtained surveys from 172 eligible students who were 76% (130) White and 53% (91) female. Observing role models and having mastery experiences supported self-efficacy with FCC during rounds (each p<0.01), while receiving feedback did not. Self-efficacy with two specific FCC tasks, relationship building and decision making (each p < 0.05), mediated the effects of these two supportive experiences on self-efficacy with FCC during rounds. Conclusions Observing role models and having mastery experiences foster students’ self-efficacy with FCC during rounds, operating through self-efficacy with key FCC tasks. Results suggest the importance of helping students gain self-efficacy in key FCC tasks before the rounds experience and helping educators implement supportive experiences during rounds. PMID:22534602

Crystal structures reveal metal-binding plasticity at the metallo-β-lactamase active site of PqqB from Pseudomonas putida

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

Tu, Xiongying; Latham, John A.; Klema, Valerie J.

PqqB is an enzyme involved in the biosynthesis of pyrroloquinoline quinone and a distal member of the metallo-β-lactamase (MBL) superfamily. PqqB lacks two residues in the conserved signature motif HxHxDH that makes up the key metal-chelating elements that can bind up to two metal ions at the active site of MBLs and other members of its superfamily. Here, we report crystal structures of PqqB bound to Mn2+, Mg2+, Cu2+, and Zn2+. These structures demonstrate that PqqB can still bind metal ions at the canonical MBL active site. The fact that PqqB can adapt its side chains to chelate a widemore » spectrum of metal ions with different coordination features on a uniform main chain scaffold demonstrates its metal-binding plasticity. This plasticity may provide insights into the structural basis of promiscuous activities found in ensembles of metal complexes within this superfamily. Furthermore, PqqB belongs to a small subclass of MBLs that contain an additional CxCxxC motif that binds a structural Zn2+. Our data support a key role for this motif in dimerization.« less

Population-based 3D genome structure analysis reveals driving forces in spatial genome organization

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

Tjong, Harianto; Li, Wenyuan; Kalhor, Reza

Conformation capture technologies (e.g., Hi-C) chart physical interactions between chromatin regions on a genome-wide scale. However, the structural variability of the genome between cells poses a great challenge to interpreting ensemble-averaged Hi-C data, particularly for long-range and interchromosomal interactions. Here, we present a probabilistic approach for deconvoluting Hi-C data into a model population of distinct diploid 3D genome structures, which facilitates the detection of chromatin interactions likely to co-occur in individual cells. Here, our approach incorporates the stochastic nature of chromosome conformations and allows a detailed analysis of alternative chromatin structure states. For example, we predict and experimentally confirm themore » presence of large centromere clusters with distinct chromosome compositions varying between individual cells. The stability of these clusters varies greatly with their chromosome identities. We show that these chromosome-specific clusters can play a key role in the overall chromosome positioning in the nucleus and stabilizing specific chromatin interactions. By explicitly considering genome structural variability, our population-based method provides an important tool for revealing novel insights into the key factors shaping the spatial genome organization.« less

Population-based 3D genome structure analysis reveals driving forces in spatial genome organization

DOE PAGES

Tjong, Harianto; Li, Wenyuan; Kalhor, Reza; ...

2016-03-07

Conformation capture technologies (e.g., Hi-C) chart physical interactions between chromatin regions on a genome-wide scale. However, the structural variability of the genome between cells poses a great challenge to interpreting ensemble-averaged Hi-C data, particularly for long-range and interchromosomal interactions. Here, we present a probabilistic approach for deconvoluting Hi-C data into a model population of distinct diploid 3D genome structures, which facilitates the detection of chromatin interactions likely to co-occur in individual cells. Here, our approach incorporates the stochastic nature of chromosome conformations and allows a detailed analysis of alternative chromatin structure states. For example, we predict and experimentally confirm themore » presence of large centromere clusters with distinct chromosome compositions varying between individual cells. The stability of these clusters varies greatly with their chromosome identities. We show that these chromosome-specific clusters can play a key role in the overall chromosome positioning in the nucleus and stabilizing specific chromatin interactions. By explicitly considering genome structural variability, our population-based method provides an important tool for revealing novel insights into the key factors shaping the spatial genome organization.« less

Deterministic chaos and fractal complexity in the dynamics of cardiovascular behavior: perspectives on a new frontier.

PubMed

Sharma, Vijay

2009-09-10

Physiological systems such as the cardiovascular system are capable of five kinds of behavior: equilibrium, periodicity, quasi-periodicity, deterministic chaos and random behavior. Systems adopt one or more these behaviors depending on the function they have evolved to perform. The emerging mathematical concepts of fractal mathematics and chaos theory are extending our ability to study physiological behavior. Fractal geometry is observed in the physical structure of pathways, networks and macroscopic structures such the vasculature and the His-Purkinje network of the heart. Fractal structure is also observed in processes in time, such as heart rate variability. Chaos theory describes the underlying dynamics of the system, and chaotic behavior is also observed at many levels, from effector molecules in the cell to heart function and blood pressure. This review discusses the role of fractal structure and chaos in the cardiovascular system at the level of the heart and blood vessels, and at the cellular level. Key functional consequences of these phenomena are highlighted, and a perspective provided on the possible evolutionary origins of chaotic behavior and fractal structure. The discussion is non-mathematical with an emphasis on the key underlying concepts.

Deterministic Chaos and Fractal Complexity in the Dynamics of Cardiovascular Behavior: Perspectives on a New Frontier

PubMed Central

Sharma, Vijay

2009-01-01

Physiological systems such as the cardiovascular system are capable of five kinds of behavior: equilibrium, periodicity, quasi-periodicity, deterministic chaos and random behavior. Systems adopt one or more these behaviors depending on the function they have evolved to perform. The emerging mathematical concepts of fractal mathematics and chaos theory are extending our ability to study physiological behavior. Fractal geometry is observed in the physical structure of pathways, networks and macroscopic structures such the vasculature and the His-Purkinje network of the heart. Fractal structure is also observed in processes in time, such as heart rate variability. Chaos theory describes the underlying dynamics of the system, and chaotic behavior is also observed at many levels, from effector molecules in the cell to heart function and blood pressure. This review discusses the role of fractal structure and chaos in the cardiovascular system at the level of the heart and blood vessels, and at the cellular level. Key functional consequences of these phenomena are highlighted, and a perspective provided on the possible evolutionary origins of chaotic behavior and fractal structure. The discussion is non-mathematical with an emphasis on the key underlying concepts. PMID:19812706

The structure of brain glycogen phosphorylase-from allosteric regulation mechanisms to clinical perspectives.

PubMed

Mathieu, Cécile; Dupret, Jean-Marie; Rodrigues Lima, Fernando

2017-02-01

Glycogen phosphorylase (GP) is the key enzyme that regulates glycogen mobilization in cells. GP is a complex allosteric enzyme that comprises a family of three isozymes: muscle GP (mGP), liver GP (lGP), and brain GP (bGP). Although the three isozymes display high similarity and catalyze the same reaction, they differ in their sensitivity to the allosteric activator adenosine monophosphate (AMP). Moreover, inactivating mutations in mGP and lGP have been known to be associated with glycogen storage diseases (McArdle and Hers disease, respectively). The determination, decades ago, of the structure of mGP and lGP have allowed to better understand the allosteric regulation of these two isoforms and the development of specific inhibitors. Despite its important role in brain glycogen metabolism, the structure of the brain GP had remained elusive. Here, we provide an overview of the human brain GP structure and its relationship with the two other members of this key family of the metabolic enzymes. We also summarize how this structure provides valuable information to understand the regulation of bGP and to design specific ligands of potential pharmacological interest. © 2016 Federation of European Biochemical Societies.

Adaptation of sensor morphology: an integrative view of perception from biologically inspired robotics perspective

PubMed Central

Nurzaman, Surya G.

2016-01-01

Sensor morphology, the morphology of a sensing mechanism which plays a role of shaping the desired response from physical stimuli from surroundings to generate signals usable as sensory information, is one of the key common aspects of sensing processes. This paper presents a structured review of researches on bioinspired sensor morphology implemented in robotic systems, and discusses the fundamental design principles. Based on literature review, we propose two key arguments: first, owing to its synthetic nature, biologically inspired robotics approach is a unique and powerful methodology to understand the role of sensor morphology and how it can evolve and adapt to its task and environment. Second, a consideration of an integrative view of perception by looking into multidisciplinary and overarching mechanisms of sensor morphology adaptation across biology and engineering enables us to extract relevant design principles that are important to extend our understanding of the unfinished concepts in sensing and perception. PMID:27499843

Contrasting faith-based and traditional substance abuse treatment programs.

PubMed

Neff, James Alan; Shorkey, Clayton T; Windsor, Liliane Cambraia

2006-01-01

This article (a) discusses the definition of faith-based substance abuse treatment programs, (b) juxtaposes Durkheim's theory regarding religion with treatment process model to highlight key dimensions of faith-based and traditional programs, and (c) presents results from a study of seven programs to identify key program dimensions and to identify differences/similarities between program types. Focus group/Concept Mapping techniques yielded a clear "spiritual activities, beliefs, and rituals" dimension, rated as significantly more important to faith-based programs. Faith-based program staff also rated "structure and discipline" as more important and "work readiness" as less important. No differences were found for "group activities/cohesion" and "role modeling/mentoring," "safe, supportive environment," and "traditional treatment modalities." Programs showed substantial similarities with regard to core social processes of treatment such as mentoring, role modeling, and social cohesion. Implications are considered for further research on treatment engagement, retention, and other outcomes.

A survey of nursing documentation, terminologies and standards in European countries

PubMed Central

Thoroddsen, Asta; Ehrenberg, Anna; Sermeus, Walter; Saranto, Kaija

2012-01-01

A survey was carried out to describe the current state of art in the use of nursing documentation, terminologies, standards and education. Key informants in European countries were targeted by the Association for Common European Nursing Diagnoses, Interventions and Outcomes (ACENDIO). Replies were received from key informants in 20 European countries. Results show that the nursing process was most often used to structure nursing documentation. Many standardized nursing terminologies were used in Europe with NANDA, NIC, NOC and ICF most frequently used. In 70% of the countries minimum requirements were available for electronic health records (EHR), but nursing not addressed specifically. Standards in use for nursing terminologies and information systems were lacking. The results should be a major concern to the nursing community in Europe. As a European platform, ACENDIO can play a role in enhancing standardization activities, and should develop its role accordingly. PMID:24199130

Siblings of individuals with first-episode psychosis: understanding their experiences and needs.

PubMed

Sin, Jacqueline; Moone, Nicki; Harris, Paul

2008-06-01

The growth of early intervention in psychosis services (EIPS) has prompted needed research to provide a robust evidence base to underpin practice. The typical service model embraces key psychosocial interventions, including family interventions. A literature review revealed a number of relevant studies that recognized the role of siblings in families affected by severe mental illness or mental impairment, but little was found about the impact of first-episode psychosis on siblings. To address this apparent oversight, we conducted a study to gain an understanding of sibling experiences. Ten siblings (ages 16 to 30) with a brother or sister diagnosed with first-episode psychosis took part in individual semi-structured interviews. The key findings were grouped in regard to emotional impact, relationships in the family, and siblings' roles and coping patterns. The study also revealed that families are able to identify positive gains out of a fundamentally negative experience.

DFT Study on Nitrite Reduction Mechanism in Copper-Containing Nitrite Reductase.

PubMed

Lintuluoto, Masami; Lintuluoto, Juha M

2016-01-12

Dissimilatory reduction of nitrite by copper-containing nitrite reductase (CuNiR) is an important step in the geobiochemical nitrogen cycle. The proposed mechanisms for the reduction of nitrite by CuNiRs include intramolecular electron and proton transfers, and these two events are understood to couple. Proton-coupled electron transfer is one of the key processes in enzyme reactions. We investigated the geometric structure of bound nitrite and the mechanism of nitrite reduction on CuNiR using density functional theory calculations. Also, the proton transfer pathway, the key residues, and their roles in the reaction mechanism were clarified in this study. In our results, the reduction of T2 Cu site promotes the proton transfer, and the hydrogen bond network around the binding site has an important role not only to stabilize the nitrite binding but also to promote the proton transfer to nitrite.

Migration in a segmented labour market.

PubMed

Gordon, I

1995-01-01

"Current research in migration is moving on from neo-classical and behavioural perspectives to a more structural approach relating to wider processes, issues of power and the particular role of employers. Within this programme a key issue for investigation is the interaction between spatial mobility and the structuring of labour markets. This paper focuses on the significance of labour market segmentation--in terms both of job stability and gender--for migration, both theoretically and through an empirical analysis of data from the UK Labour Force Survey on sponsored and unsponsored moves." excerpt

Crystal structures of ASK1-inhibtor complexes provide a platform for structure-based drug design

PubMed Central

Singh, Onkar; Shillings, Anthony; Craggs, Peter; Wall, Ian; Rowland, Paul; Skarzynski, Tadeusz; Hobbs, Clare I; Hardwick, Phil; Tanner, Rob; Blunt, Michelle; Witty, David R; Smith, Kathrine J

2013-01-01

ASK1, a member of the MAPK Kinase Kinase family of proteins has been shown to play a key role in cancer, neurodegeneration and cardiovascular diseases and is emerging as a possible drug target. Here we describe a ‘replacement-soaking’ method that has enabled the high-throughput X-ray structure determination of ASK1/ligand complexes. Comparison of the X-ray structures of five ASK1/ligand complexes from 3 different chemotypes illustrates that the ASK1 ATP binding site is able to accommodate a range of chemical diversity and different binding modes. The replacement-soaking system is also able to tolerate some protein flexibility. This crystal system provides a robust platform for ASK1/ligand structure determination and future structure based drug design. PMID:23776076

Structure and self-assembly of the calcium binding matrix protein of human metapneumovirus.

PubMed

Leyrat, Cedric; Renner, Max; Harlos, Karl; Huiskonen, Juha T; Grimes, Jonathan M

2014-01-07

The matrix protein (M) of paramyxoviruses plays a key role in determining virion morphology by directing viral assembly and budding. Here, we report the crystal structure of the human metapneumovirus M at 2.8 Å resolution in its native dimeric state. The structure reveals the presence of a high-affinity Ca²⁺ binding site. Molecular dynamics simulations (MDS) predict a secondary lower-affinity site that correlates well with data from fluorescence-based thermal shift assays. By combining small-angle X-ray scattering with MDS and ensemble analysis, we captured the structure and dynamics of M in solution. Our analysis reveals a large positively charged patch on the protein surface that is involved in membrane interaction. Structural analysis of DOPC-induced polymerization of M into helical filaments using electron microscopy leads to a model of M self-assembly. The conservation of the Ca²⁺ binding sites suggests a role for calcium in the replication and morphogenesis of pneumoviruses. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Exploration of priority actions for strengthening the role of nurses in achieving universal health coverage

PubMed Central

Maaitah, Rowaida Al; AbuAlRub, Raeda Fawzi

2017-01-01

ABSTRACT Objective: to explore priority actions for strengthening the role of Advanced Practice Nurses (APNs) towards the achievement of Universal Health Converge (UHC) as perceived by health key informants in Jordan. Methods: an exploratory qualitative design, using a semi-structured survey, was utilized. A purposive sample of seventeen key informants from various nursing and health care sectors was recruited for the purpose of the study. Content analysis utilizing the five-stage framework approach was used for data analysis. Results: the findings revealed that policy and regulation, nursing education, research, and workforce were identified as the main elements that influence the role of APNs in contributing to the achievement of UHC. Priority actions were identified by the participants for the main four elements. Conclusion: study findings confirm the need to strengthen the role of APNs to achieve UHC through a major transformation in nursing education, practice, research, leadership, and regulatory system. Nurses should unite to come up with solid nursing competencies related to APNs, PHC, UHC, leadership and policy making to strengthen their position as main actors in influencing the health care system and evidence creation. PMID:28146176

The Diverse Roles of Arrestin Scaffolds in G Protein-Coupled Receptor Signaling.

PubMed

Peterson, Yuri K; Luttrell, Louis M

2017-07-01

The visual/ β -arrestins, a small family of proteins originally described for their role in the desensitization and intracellular trafficking of G protein-coupled receptors (GPCRs), have emerged as key regulators of multiple signaling pathways. Evolutionarily related to a larger group of regulatory scaffolds that share a common arrestin fold, the visual/ β -arrestins acquired the capacity to detect and bind activated GPCRs on the plasma membrane, which enables them to control GPCR desensitization, internalization, and intracellular trafficking. By acting as scaffolds that bind key pathway intermediates, visual/ β -arrestins both influence the tonic level of pathway activity in cells and, in some cases, serve as ligand-regulated scaffolds for GPCR-mediated signaling. Growing evidence supports the physiologic and pathophysiologic roles of arrestins and underscores their potential as therapeutic targets. Circumventing arrestin-dependent GPCR desensitization may alleviate the problem of tachyphylaxis to drugs that target GPCRs, and find application in the management of chronic pain, asthma, and psychiatric illness. As signaling scaffolds, arrestins are also central regulators of pathways controlling cell growth, migration, and survival, suggesting that manipulating their scaffolding functions may be beneficial in inflammatory diseases, fibrosis, and cancer. In this review we examine the structure-function relationships that enable arrestins to perform their diverse roles, addressing arrestin structure at the molecular level, the relationship between arrestin conformation and function, and sites of interaction between arrestins, GPCRs, and nonreceptor-binding partners. We conclude with a discussion of arrestins as therapeutic targets and the settings in which manipulating arrestin function might be of clinical benefit. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Communication that heals: mindful communication practices from palliative care leaders.

PubMed

Omilion-Hodges, Leah M; Swords, Nathan M

2016-01-01

Though research has begun to highlight the centrality of communication in palliative care, studies have yet to focus on the use of mindful communication. Mindful communication is associated with increases in patient care and decreases in physician burnout. Through in-depth, semi-structured interviews the authors sought mindful communication practices from palliative care leaders in American Hospital Association Circle of Life® award-wining units. Four key mindful communication practices emerged: Know your audience, ask questions, discard scripts, and recognize your role. The discussion articulates how key mindful communication practices may be used as a stage model, where key practices may be used individually or in concert, by sole practitioners or within interdisciplinary teams and by new and seasoned clinicians. Theoretical contributions and areas for future inquiry are also discussed.

Skeletal biology: Where matrix meets mineral

PubMed Central

Young, Marian F.

2017-01-01

The skeleton is unique from all other tissues in the body because of its ability to mineralize. The incorporation of mineral into bones and teeth is essential to give them strength and structure for body support and function. For years, researchers have wondered how mineralized tissues form and repair. A major focus in this context has been on the role of the extracellular matrix, which harbors key regulators of the mineralization process. In this introductory minireview, we will review some key concepts of matrix biology as it related to mineralized tissues. Concurrently, we will highlight the subject of this special issue covering many aspects of mineralized tissues, including bones and teeth and their associated structures cartilage and tendon. Areas of emphasis are on the generation and analysis of new animal models with permutations of matrix components as well as the development of new approaches for tissue engineering for repair of damaged hard tissue. In assembling key topics on mineralized tissues written by leaders in our field, we hope the reader will get a broad view of the topic and all of its fascinating complexities. PMID:27131884

Role of filament annealing in the kinetics and thermodynamics of nucleated polymerization.

PubMed

Michaels, Thomas C T; Knowles, Tuomas P J

2014-06-07

The formation of nanoscale protein filaments from soluble precursor molecules through nucleated polymerization is a common form of supra-molecular assembly phenomenon. This process underlies the generation of a range of both functional and pathological structures in nature. Filament breakage has emerged as a key process controlling the kinetics of the growth reaction since it increases the number of filament ends in the system that can act as growth sites. In order to ensure microscopic reversibility, however, the inverse process of fragmentation, end-to-end annealing of filaments, is a necessary component of a consistent description of such systems. Here, we combine Smoluchowski kinetics with nucleated polymerization models to generate a master equation description of protein fibrillization, where filamentous structures can undergo end-to-end association, in addition to elongation, fragmentation, and nucleation processes. We obtain self-consistent closed-form expressions for the growth kinetics and discuss the key physics that emerges from considering filament fusion relative to current fragmentation only models. Furthermore, we study the key time scales that describe relaxation to equilibrium.

Modeling, molecular dynamics, and docking assessment of transcription factor rho: a potential drug target in Brucella melitensis 16M

PubMed Central

Pradeepkiran, Jangampalli Adi; Kumar, Konidala Kranthi; Kumar, Yellapu Nanda; Bhaskar, Matcha

2015-01-01

The zoonotic disease brucellosis, a chronic condition in humans affecting renal and cardiac systems and causing osteoarthritis, is caused by Brucella, a genus of Gram-negative, facultative, intracellular pathogens. The mode of transmission and the virulence of the pathogens are still enigmatic. Transcription regulatory elements, such as rho proteins, play an important role in the termination of transcription and/or the selection of genes in Brucella. Adverse effects of the transcription inhibitors play a key role in the non-successive transcription challenges faced by the pathogens. In the investigation presented here, we computationally predicted the transcription termination factor rho (TtFRho) inhibitors against Brucella melitensis 16M via a structure-based method. In view the unknown nature of its crystal structure, we constructed a robust three-dimensional homology model of TtFRho’s structure by comparative modeling with the crystal structure of the Escherichia coli TtFRho (Protein Data Bank ID: 1PVO) as a template in MODELLER (v 9.10). The modeled structure was optimized by applying a molecular dynamics simulation for 2 ns with the CHARMM (Chemistry at HARvard Macromolecular Mechanics) 27 force field in NAMD (NAnoscale Molecular Dynamics program; v 2.9) and then evaluated by calculating the stereochemical quality of the protein. The flexible docking for the interaction phenomenon of the template consists of ligand-related inhibitor molecules from the ZINC (ZINC Is Not Commercial) database using a structure-based virtual screening strategy against minimized TtFRho. Docking simulations revealed two inhibitors compounds – ZINC24934545 and ZINC72319544 – that showed high binding affinity among 2,829 drug analogs that bind with key active-site residues; these residues are considered for protein-ligand binding and unbinding pathways via steered molecular dynamics simulations. Arg215 in the model plays an important role in the stability of the protein-ligand complex via a hydrogen bonding interaction by aromatic-π contacts, and the ADMET (absorption, distribution, metabolism, and excretion) analysis of best leads indicate nontoxic in nature with good potential for drug development. PMID:25848225

Developing Master Keys to Brain Pathology, Cancer and Aging from the Structural Biology of Proteins Controlling Reactive Oxygen Species and DNA Repair

PubMed Central

Perry, J. Jefferson P.; Fan, Li; Tainer, John A.

2007-01-01

This review is focused on proteins with key roles in pathways controlling either reactive oxygen species or DNA damage responses, both of which are essential for preserving the nervous system. An imbalance of reactive oxygen species or inappropriate DNA damage response likely causes mutational or cytotoxic outcomes, which may lead to cancer and/or aging phenotypes. Moreover, individuals with hereditary disorders in proteins of these cellular pathways have significant neurological abnormalities. Mutations in a superoxide dismutase, which removes oxygen free radicals, may cause the neurodegenerative disease amyotrophic lateral sclerosis. Additionally, DNA repair disorders that affect the brain to varying extents include ataxia-telangiectasia-like disorder, Cockayne syndrome or Werner syndrome. Here, we highlight recent advances gained through structural biochemistry studies on enzymes linked to these disorders and other related enzymes acting within the same cellular pathways. We describe the current understanding of how these vital proteins coordinate chemical steps and integrate cellular signaling and response events. Significantly, these structural studies may provide a set of master keys to developing a unified understanding of the survival mechanisms utilized after insults by reactive oxygen species and genotoxic agents, and also provide a basis for developing an informed intervention in brain tumor and neurodegenerative disease progression. PMID:17174478

Moderno love: sexual role-based identities and HIV/STI prevention among men who have sex with men in Lima, Peru.

PubMed

Clark, Jesse; Salvatierra, Javier; Segura, Eddy; Salazar, Ximena; Konda, Kelika; Perez-Brumer, Amaya; Hall, Eric; Klausner, Jeffrey; Caceres, Carlos; Coates, Thomas

2013-05-01

Role-based sexual identities structure male same-sex partnerships and influence HIV/STI epidemiology among MSM in Latin America. We explored shifting relationships between sexual roles, identities and practices among MSM in Lima, Peru, and implications for HIV/STI prevention. Patterns of HIV/STI epidemiology reflected differential risks for transmission within role-based partnerships with relatively low prevalences of HIV, syphilis, and HSV-2 but higher prevalences of urethral gonorrhea/chlamydia among activo MSM compared with moderno and pasivo participants. Qualitative analysis of how MSM in Peru integrate sexual identities, roles, and practices identified four key themes: pasivo role as a gay approximation of cultural femininity; activo role as a heterosexual consolidation of masculinity; moderno role as a masculine reconceptualization of gay identity; and role-based identities as social determinants of partnership, network, and community formation. The concept of role-based sexual identities provides a framework for HIV prevention for Latin American MSM that integrates sexual identities, practices, partnerships, and networks.

Moderno Love: Sexual Role-Based Identities and HIV/STI Prevention Among Men Who Have Sex with Men in Lima, Peru

PubMed Central

Salvatierra, Javier; Segura, Eddy; Salazar, Ximena; Konda, Kelika; Perez-Brumer, Amaya; Hall, Eric; Klausner, Jeffrey; Caceres, Carlos; Coates, Thomas

2012-01-01

Role-based sexual identities structure male same-sex partnerships and influence HIV/STI epidemiology among MSM in Latin America. We explored shifting relationships between sexual roles, identities and practices among MSM in Lima, Peru, and implications for HIV/STI prevention. Patterns of HIV/STI epidemiology reflected differential risks for transmission within role-based partnerships with relatively low prevalences of HIV, syphilis, and HSV-2 but higher prevalences of urethral gonorrhea/chlamydia among activo MSM compared with moderno and pasivo participants. Qualitative analysis of how MSM in Peru integrate sexual identities, roles, and practices identified four key themes: pasivo role as a gay approximation of cultural femininity; activo role as a heterosexual consolidation of masculinity; moderno role as a masculine reconceptualization of gay identity; and role-based identities as social determinants of partnership, network, and community formation. The concept of role-based sexual identities provides a framework for HIV prevention for Latin American MSM that integrates sexual identities, practices, partnerships, and networks. PMID:22614747

Fibre Optic Sensors for Structural Health Monitoring of Aircraft Composite Structures: Recent Advances and Applications

PubMed Central

Di Sante, Raffaella

2015-01-01

In-service structural health monitoring of composite aircraft structures plays a key role in the assessment of their performance and integrity. In recent years, Fibre Optic Sensors (FOS) have proved to be a potentially excellent technique for real-time in-situ monitoring of these structures due to their numerous advantages, such as immunity to electromagnetic interference, small size, light weight, durability, and high bandwidth, which allows a great number of sensors to operate in the same system, and the possibility to be integrated within the material. However, more effort is still needed to bring the technology to a fully mature readiness level. In this paper, recent research and applications in structural health monitoring of composite aircraft structures using FOS have been critically reviewed, considering both the multi-point and distributed sensing techniques. PMID:26263987

Fibre Optic Sensors for Structural Health Monitoring of Aircraft Composite Structures: Recent Advances and Applications.

PubMed

Di Sante, Raffaella

2015-07-30

In-service structural health monitoring of composite aircraft structures plays a key role in the assessment of their performance and integrity. In recent years, Fibre Optic Sensors (FOS) have proved to be a potentially excellent technique for real-time in-situ monitoring of these structures due to their numerous advantages, such as immunity to electromagnetic interference, small size, light weight, durability, and high bandwidth, which allows a great number of sensors to operate in the same system, and the possibility to be integrated within the material. However, more effort is still needed to bring the technology to a fully mature readiness level. In this paper, recent research and applications in structural health monitoring of composite aircraft structures using FOS have been critically reviewed, considering both the multi-point and distributed sensing techniques.

An evaluation of the critical care assistant role within an acute NHS Trust Critical Care Unit.

PubMed

McGloin, Sarah; Knowles, Judie

2005-01-01

This study provides an evaluation of a training programme designed for developing six critical care assistants to work alongside registered nurses to care for patients within the critical care environment. The programme was run as a pilot funded from the Department of Health's 'critical care bid'. At 18 months long, the programme incorporated a foundation programme, and National Vocational Qualification (NVQ) level 3 in care and adapted Operating Department Practitioner (ODP) NVQ units. Six critical care assistants successfully completed the programme; however, they all then left the unit to undertake further study for pre-registration nursing qualifications. Upon evaluation, a number of key issues were identified. Clear definition of the critical care assistants's role is essential as are dedicated practice development staff, who focus purely on developing the critical care assistant role. More importantly, however, with such key changes in the staffing structure within critical care units, appropriate change management techniques should be employed, ensuring that all staff contributing to the training and development are fully involved from the start.

Genome-Wide Identification of the Alba Gene Family in Plants and Stress-Responsive Expression of the Rice Alba Genes.

PubMed

Verma, Jitendra Kumar; Wardhan, Vijay; Singh, Deepali; Chakraborty, Subhra; Chakraborty, Niranjan

2018-03-28

Architectural proteins play key roles in genome construction and regulate the expression of many genes, albeit the modulation of genome plasticity by these proteins is largely unknown. A critical screening of the architectural proteins in five crop species, viz., Oryza sativa , Zea mays , Sorghum bicolor , Cicer arietinum , and Vitis vinifera , and in the model plant Arabidopsis thaliana along with evolutionary relevant species such as Chlamydomonas reinhardtii , Physcomitrella patens , and Amborella trichopoda , revealed 9, 20, 10, 7, 7, 6, 1, 4, and 4 Alba (acetylation lowers binding affinity) genes, respectively. A phylogenetic analysis of the genes and of their counterparts in other plant species indicated evolutionary conservation and diversification. In each group, the structural components of the genes and motifs showed significant conservation. The chromosomal location of the Alba genes of rice ( OsAlba ), showed an unequal distribution on 8 of its 12 chromosomes. The expression profiles of the OsAlba genes indicated a distinct tissue-specific expression in the seedling, vegetative, and reproductive stages. The quantitative real-time PCR (qRT-PCR) analysis of the OsAlba genes confirmed their stress-inducible expression under multivariate environmental conditions and phytohormone treatments. The evaluation of the regulatory elements in 68 Alba genes from the 9 species studied led to the identification of conserved motifs and overlapping microRNA (miRNA) target sites, suggesting the conservation of their function in related proteins and a divergence in their biological roles across species. The 3D structure and the prediction of putative ligands and their binding sites for OsAlba proteins offered a key insight into the structure-function relationship. These results provide a comprehensive overview of the subtle genetic diversification of the OsAlba genes, which will help in elucidating their functional role in plants.

Neighborhood Age Structure and its Implications for Health

PubMed Central

2006-01-01

Age structure at the neighborhood level is rarely considered in contextual studies of health. However, age structure can play a critical role in shaping community life, the availability of resources, and the opportunities for social engagement—all factors that, research suggests, have direct and indirect effects on health. Age structure can be theorized as a compositional effect and as a contextual effect. In addition, the dynamic nature of age structure and the utility of a life course perspective as applied to neighborhood effects research merits attention. Four Chicago neighborhoods are summarized to illustrate how age structure varies across small space, suggesting that neighborhood age structure should be considered a key structural covariate in contextual research on health. Considering age structure implies incorporating not only meaningful cut points for important age groups (e.g., proportion 65 years and over) but attention to the shape of the distribution as well. PMID:16865558

Design and synthesis of emodin derivatives as novel inhibitors of ATP-citrate lyase.

PubMed

Koerner, Steffi K; Hanai, Jun-Ichi; Bai, Sha; Jernigan, Finith E; Oki, Miwa; Komaba, Chieko; Shuto, Emi; Sukhatme, Vikas P; Sun, Lijun

2017-01-27

Aberrant cellular metabolism drives cancer proliferation and metastasis. ATP citrate lyase (ACL) plays a critical role in generating cytosolic acetyl CoA, a key building block for de novo fatty acid and cholesterol biosynthesis. ACL is overexpressed in cancer cells, and siRNA knockdown of ACL limits cancer cell proliferation and reduces cancer stemness. We characterized a new class of ACL inhibitors bearing the key structural feature of the natural product emodin. Structure-activity relationship (SAR) study led to the identification of 1d as a potent lead that demonstrated dose-dependent inhibition of proliferation and cancer stemness of the A549 lung cancer cell line. Computational modeling indicates this class of inhibitors occupies an allosteric binding site and blocks the entrance of the substrate citrate to its binding site. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Guiding lead optimization with GPCR structure modeling and molecular dynamics.

PubMed

Heifetz, Alexander; James, Tim; Morao, Inaki; Bodkin, Michael J; Biggin, Philip C

2016-10-01

G-protein coupled receptor (GPCR) modeling approaches are widely used in the hit-to-lead and lead optimization stages of drug discovery. Modern protocols that involve molecular dynamics simulation can address key issues such as the free energy of binding (affinity), ligand-induced GPCR flexibility, ligand binding kinetics, conserved water positions and their role in ligand binding and the effects of mutations. The goals of these calculations are to predict the structures of the complexes between existing ligands and their receptors, to understand the key interactions and to utilize these insights in the design of new molecules with improved binding, selectivity or other pharmacological properties. In this review we present a brief survey of various computational approaches illustrated through a hierarchical GPCR modeling protocol and its prospective application in three industrial drug discovery projects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Insights on synergy of materials and structures in biomimetic platelet-matrix composites

NASA Astrophysics Data System (ADS)

Sakhavand, Navid; Shahsavari, Rouzbeh

2018-01-01

Hybrid materials such as biomimetic platelet-matrix composites are in high demand to confer low weight and multifunctional mechanical properties. This letter reports interfacial-bond regulated assembly of polymers on cement-an archetype model with significant infrastructure applications. We demonstrate a series of 20+ molecular dynamics studies on decoding and optimizing the complex interfacial interactions including the role and types of various heterogeneous, competing interfacial bonds that are key to adhesion and interfacial strength. Our results show an existence of an optimum overlap length scale (˜15 nm) between polymers and cement crystals, exhibiting the best balance of strength, toughness, stiffness, and ductility for the composite. This finding, combined with the fundamental insights into the nature of interfacial bonds, provides key hypotheses for selection and processing of constituents to deliberate the best synergy in the structure and materials of platelet-matrix composites.

Automatic transfer function design for medical visualization using visibility distributions and projective color mapping.

PubMed

Cai, Lile; Tay, Wei-Liang; Nguyen, Binh P; Chui, Chee-Kong; Ong, Sim-Heng

2013-01-01

Transfer functions play a key role in volume rendering of medical data, but transfer function manipulation is unintuitive and can be time-consuming; achieving an optimal visualization of patient anatomy or pathology is difficult. To overcome this problem, we present a system for automatic transfer function design based on visibility distribution and projective color mapping. Instead of assigning opacity directly based on voxel intensity and gradient magnitude, the opacity transfer function is automatically derived by matching the observed visibility distribution to a target visibility distribution. An automatic color assignment scheme based on projective mapping is proposed to assign colors that allow for the visual discrimination of different structures, while also reflecting the degree of similarity between them. When our method was tested on several medical volumetric datasets, the key structures within the volume were clearly visualized with minimal user intervention. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

A framework to support human factors of automation in railway intelligent infrastructure.

PubMed

Dadashi, Nastaran; Wilson, John R; Golightly, David; Sharples, Sarah

2014-01-01

Technological and organisational advances have increased the potential for remote access and proactive monitoring of the infrastructure in various domains and sectors - water and sewage, oil and gas and transport. Intelligent Infrastructure (II) is an architecture that potentially enables the generation of timely and relevant information about the state of any type of infrastructure asset, providing a basis for reliable decision-making. This paper reports an exploratory study to understand the concepts and human factors associated with II in the railway, largely drawing from structured interviews with key industry decision-makers and attachment to pilot projects. Outputs from the study include a data-processing framework defining the key human factors at different levels of the data structure within a railway II system and a system-level representation. The framework and other study findings will form a basis for human factors contributions to systems design elements such as information interfaces and role specifications.

Modelling students' knowledge organisation: Genealogical conceptual networks

NASA Astrophysics Data System (ADS)

Koponen, Ismo T.; Nousiainen, Maija

2018-04-01

Learning scientific knowledge is largely based on understanding what are its key concepts and how they are related. The relational structure of concepts also affects how concepts are introduced in teaching scientific knowledge. We model here how students organise their knowledge when they represent their understanding of how physics concepts are related. The model is based on assumptions that students use simple basic linking-motifs in introducing new concepts and mostly relate them to concepts that were introduced a few steps earlier, i.e. following a genealogical ordering. The resulting genealogical networks have relatively high local clustering coefficients of nodes but otherwise resemble networks obtained with an identical degree distribution of nodes but with random linking between them (i.e. the configuration-model). However, a few key nodes having a special structural role emerge and these nodes have a higher than average communicability betweenness centralities. These features agree with the empirically found properties of students' concept networks.

Ferromagnetically filled carbon nano-onions: the key role of sulfur in dimensional, structural and electric control

PubMed Central

Medranda, D.; Borowiec, J.; Zhang, Xiao; Wang, S.; Yan, K.; Zhang, J.; He, Y.; Ivaturi, S.

2018-01-01

A key challenge in the fabrication of ferromagnetically filled carbon nano-onions (CNOs) is the control of their thickness, dimensions and electric properties. Up to now literature works have mainly focused on the encapsulation of different types of ferromagnetic materials including α-Fe, Fe3C, Co, FeCo, FePd3 and others within CNOs. However, no report has yet shown a suitable method for controlling both the number of shells, diameter and electric properties of the produced CNOs. Here, we demonstrate an advanced chemical vapour deposition approach in which the use of small quantities of sulfur during the pyrolysis of ferrocene allows for the control of (i) the diameter of the CNOs, (ii) the number of shells and (iii) the electric properties. We demonstrate the morphological, structural, electric and magnetic properties of these new types of CNOs by using SEM, XRD, TEM, HRTEM, EIS and VSM techniques. PMID:29410810

Are Models Easier to Understand than Code? An Empirical Study on Comprehension of Entity-Relationship (ER) Models vs. Structured Query Language (SQL) Code

ERIC Educational Resources Information Center

Sanchez, Pablo; Zorrilla, Marta; Duque, Rafael; Nieto-Reyes, Alicia

2011-01-01

Models in Software Engineering are considered as abstract representations of software systems. Models highlight relevant details for a certain purpose, whereas irrelevant ones are hidden. Models are supposed to make system comprehension easier by reducing complexity. Therefore, models should play a key role in education, since they would ease the…

Novel approaches for targeting the adenosine A2A receptor.

PubMed

Yuan, Gengyang; Gedeon, Nicholas G; Jankins, Tanner C; Jones, Graham B

2015-01-01

The adenosine A2A receptor (A2AR) represents a drug target for a wide spectrum of diseases. Approaches for targeting this membrane-bound protein have been greatly advanced by new stabilization techniques. The resulting X-ray crystal structures and subsequent analyses provide deep insight to the A2AR from both static and dynamic perspectives. Application of this, along with other biophysical methods combined with fragment-based drug design (FBDD), has become a standard approach in targeting A2AR. Complementarities of in silico screening based- and biophysical screening assisted- FBDD are likely to feature in future approaches in identifying novel ligands against this key receptor. This review describes evolution of the above approaches for targeting A2AR and highlights key modulators identified. It includes a review of: adenosine receptor structures, homology modeling, X-ray structural analysis, rational drug design, biophysical methods, FBDD and in silico screening. As a drug target, the A2AR is attractive as its function plays a role in a wide spectrum of diseases including oncologic, inflammatory, Parkinson's and cardiovascular diseases. Although traditional approaches such as high-throughput screening and homology model-based virtual screening (VS) have played a role in targeting A2AR, numerous shortcomings have generally restricted their applications to specific ligand families. Using stabilization methods for crystallization, X-ray structures of A2AR have greatly accelerated drug discovery and influenced development of biophysical-in silico hybrid screening methods. Application of these new methods to other ARs and G-protein-coupled receptors is anticipated in the future.

Adsorption, folding, and packing of an amphiphilic peptide at the air/water interface.

PubMed

Engin, Ozge; Sayar, Mehmet

2012-02-23

Peptide oligomers play an essential role as model compounds for identifying key motifs in protein structure formation and protein aggregation. Here, we present our results, based on extensive molecular dynamics simulations, on adsorption, folding, and packing within a surface monolayer of an amphiphilic peptide at the air/water interface. Experimental results suggest that these molecules spontaneously form ordered monolayers at the interface, adopting a β-hairpin-like structure within the surface layer. Our results reveal that the β-hairpin structure can be observed both in bulk and at the air/water interface. However, the presence of an interface leads to ideal partitioning of the hydrophobic and hydrophilic residues, and therefore reduces the conformational space for the molecule and increases the stability of the hairpin structure. We obtained the adsorption free energy of a single β-hairpin at the air/water interface, and analyzed the enthalpic and entropic contributions. The adsorption process is favored by two main factors: (1) Free-energy reduction due to desolvation of the hydrophobic side chains of the peptide and release of the water molecules which form a cage around these hydrophobic groups in bulk water. (2) Reduction of the total air/water contact area at the interface upon adsorption of the peptide amphiphile. By performing mutations on the original molecule, we demonstrated the relative role of key design features of the peptide. Finally, by analyzing the potential of mean force among two peptides at the interface, we investigated possible packing mechanisms for these molecules within the surface monolayer. © 2012 American Chemical Society

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

Barrila, J.; Gabelli, S; Bacha, U

Coronaviruses are responsible for a significant proportion of annual respiratory and enteric infections in humans and other mammals. The most prominent of these viruses is the severe acute respiratory syndrome coronavirus (SARS-CoV) which causes acute respiratory and gastrointestinal infection in humans. The coronavirus main protease, 3CL{sup pro}, is a key target for broad-spectrum antiviral development because of its critical role in viral maturation and high degree of structural conservation among coronaviruses. Dimerization is an indispensable requirement for the function of SARS 3CL{sup pro} and is regulated through mechanisms involving both direct and long-range interactions in the enzyme. While many ofmore » the binding interactions at the dimerization interface have been extensively studied, those that are important for long-range control are not well-understood. Characterization of these dimerization mechanisms is important for the structure-based design of new treatments targeting coronavirus-based infections. Here we report that Asn28, a residue 11 {angstrom} from the closest residue in the opposing monomer, is essential for the enzymatic activity and dimerization of SARS 3CLpro. Mutation of this residue to alanine almost completely inactivates the enzyme and results in a 19.2-fold decrease in the dimerization K{sub d}. The crystallographic structure of the N28A mutant determined at 2.35 {angstrom} resolution reveals the critical role of Asn28 in maintaining the structural integrity of the active site and in orienting key residues involved in binding at the dimer interface and substrate catalysis. These findings provide deeper insight into complex mechanisms regulating the activity and dimerization of SARS 3CL{sup pro}.« less

Obesity and Aging: Consequences for Cognition, Brain Structure, and Brain Function.

PubMed

Bischof, Gérard N; Park, Denise C

2015-01-01

This review focuses on the relationship between obesity and aging and how these interact to affect cognitive function. The topics covered are guided by the Scaffolding Theory of Aging and Cognition (STAC [Park and Reuter-Lorenz. Annu Rev Psychol 2009;60:173-96]-a conceptual model designed to relate brain structure and function to one's level of cognitive ability. The initial literature search was focused on normal aging and was guided by the key words, "aging, cognition, and obesity" in PubMed. In a second search, we added key words related to neuropathology including words "Alzheimer's disease," "vascular dementia," and "mild cognitive impairment." The data suggest that being overweight or obese in midlife may be more detrimental to subsequent age-related cognitive decline than being overweight or obese at later stages of the life span. These effects are likely mediated by the accelerated effects obesity has on the integrity of neural structures, including both gray and white matter. Further epidemiological studies have provided evidence that obesity in midlife is linked to an increased risk for Alzheimer's disease and vascular dementia, most likely via an increased accumulation of Alzheimer's disease pathology. Although it is clear that obesity negatively affects cognition, more work is needed to better understand how aging plays a role and how brain structure and brain function might mediate the relationship of obesity and age on cognition. Guided by the STAC and the STAC-R models, we provide a roadmap for future investigations of the role of obesity on cognition across the life span.

Obesity and Aging: Consequences for Cognition, Brain Structure and Brain Function

PubMed Central

Bischof, Gérard N.; Park, Denise C.

2017-01-01

Objective This review focuses on the relationship between obesity and aging and how these interact together to affect cognitive function. The topics covered are guided by the Scaffolding Theory of Aging and Cognition (STAC; Park & Reuter-Lorenz, 2009—a conceptual model designed to relate brain structure and function to one’s level of cognitive ability. Methods The initial literature search was focused on normal aging and was guided by the key words, “aging, cognition, and obesity” in “PUBMED”. In a second search we added key words related to neuropathology including words “Alzheimer’s Disease”, “Vascular dementia” (VaD) and “Mild Cognitive Impairment” (MCI). Results The data suggest that being overweight or obese in midlife may be more detrimental to subsequent age-related cognitive decline than being overweight or obese at later stages of the lifespan. These effects are likely mediated by the accelerated effects obesity has on the integrity of neural structures, including both gray and white matter. Further epidemiological studies have provided evidence that obesity in mid-life is linked to an increased risk for AD and VaD, most likely via an increased accumulation of AD pathology. Conclusion While it is clear that obesity negatively affects cognition, more work is needed to better understand how aging plays a role and how brain structure and brain function might mediate the relationship of obesity and age on cognition. Guided by the STAC and the STAC-R models, we provide a roadmap for future investigations of the role of obesity on cognition across the lifespan. PMID:26107577

Determinants of community structure of zooplankton in heavily polluted river ecosystems

NASA Astrophysics Data System (ADS)

Xiong, Wei; Li, Jie; Chen, Yiyong; Shan, Baoqing; Wang, Weimin; Zhan, Aibin

2016-02-01

River ecosystems are among the most affected habitats globally by human activities, such as the release of chemical pollutants. However, it remains largely unknown how and to what extent many communities such as zooplankton are affected by these environmental stressors in river ecosystems. Here, we aim to determine major factors responsible for shaping community structure of zooplankton in heavily polluted river ecosystems. Specially, we use rotifers in the Haihe River Basin (HRB) in North China as a case study to test the hypothesis that species sorting (i.e. species are “filtered” by environmental factors and occur at environmental suitable sites) plays a key role in determining community structure at the basin level. Based on an analysis of 94 sites across the plain region of HRB, we found evidence that both local and regional factors could affect rotifer community structure. Interestingly, further analyses indicated that local factors played a more important role in determining community structure. Thus, our results support the species sorting hypothesis in highly polluted rivers, suggesting that local environmental constraints, such as environmental pollution caused by human activities, can be stronger than dispersal limitation caused by regional factors to shape local community structure of zooplankton at the basin level.

SEACAS Theory Manuals: Part II. Nonlinear Continuum Mechanics

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

Attaway, S.W.; Laursen, T.A.; Zadoks, R.I.

1998-09-01

This report summarizes the key continuum mechanics concepts required for the systematic prescription and numerical solution of finite deformation solid mechanics problems. Topics surveyed include measures of deformation appropriate for media undergoing large deformations, stress measures appropriate for such problems, balance laws and their role in nonlinear continuum mechanics, the role of frame indifference in description of large deformation response, and the extension of these theories to encompass two dimensional idealizations, structural idealizations, and rigid body behavior. There are three companion reports that describe the problem formulation, constitutive modeling, and finite element technology for nonlinear continuum mechanics systems.

Arabinogalactan-proteins and the research challenges for these enigmatic plant cell surface proteoglycans

PubMed Central

Tan, Li; Showalter, Allan M.; Egelund, Jack; Hernandez-Sanchez, Arianna; Doblin, Monika S.; Bacic, Antony

2012-01-01

Arabinogalactan-proteins (AGPs) are complex glycoconjugates that are commonly found at the cell surface and in secretions of plants. Their location and diversity of structures have made them attractive targets as modulators of plant development but definitive proof of their direct role(s) in biological processes remains elusive. Here we overview the current state of knowledge on AGPs, identify key challenges impeding progress in the field and propose approaches using modern bioinformatic, (bio)chemical, cell biological, molecular and genetic techniques that could be applied to redress these gaps in our knowledge. PMID:22754559

Proteins and Their Interacting Partners: An Introduction to Protein-Ligand Binding Site Prediction Methods.

PubMed

Roche, Daniel Barry; Brackenridge, Danielle Allison; McGuffin, Liam James

2015-12-15

Elucidating the biological and biochemical roles of proteins, and subsequently determining their interacting partners, can be difficult and time consuming using in vitro and/or in vivo methods, and consequently the majority of newly sequenced proteins will have unknown structures and functions. However, in silico methods for predicting protein-ligand binding sites and protein biochemical functions offer an alternative practical solution. The characterisation of protein-ligand binding sites is essential for investigating new functional roles, which can impact the major biological research spheres of health, food, and energy security. In this review we discuss the role in silico methods play in 3D modelling of protein-ligand binding sites, along with their role in predicting biochemical functionality. In addition, we describe in detail some of the key alternative in silico prediction approaches that are available, as well as discussing the Critical Assessment of Techniques for Protein Structure Prediction (CASP) and the Continuous Automated Model EvaluatiOn (CAMEO) projects, and their impact on developments in the field. Furthermore, we discuss the importance of protein function prediction methods for tackling 21st century problems.

Forging the ring: from fungal septins' divergent roles in morphology, septation and virulence to factors contributing to their assembly into higher order structures.

PubMed

Vargas-Muñiz, Jose M; Juvvadi, Praveen R; Steinbach, William J

2016-09-01

Septins are a conserved family of GTP-binding proteins that are distributed across different lineages of the eukaryotes, with the exception of plants. Septins perform a myriad of functions in fungal cells, ranging from controlling morphogenetic events to contributing to host tissue invasion and virulence. One key attribute of the septins is their ability to assemble into heterooligomeric complexes that organizse into higher order structures. In addition to the established role of septins in the model budding yeast, Saccharomyces cerevisiae, their importance in other fungi recently emerges. While newer roles for septins are being uncovered in these fungi, the mechanism of how septins assemble into a complex and their regulation is only beginning to be comprehended. In this review, we summarize recent findings on the role of septins in different fungi and focus on how the septin complexes of different fungi are organized in vitro and in vivo. Furthermore, we discuss on how phosphorylation/dephosphorylation can serve as an important mechanism of septin complex assembly and regulation.

Metal surface coloration by oxide periodic structures formed with nanosecond laser pulses

NASA Astrophysics Data System (ADS)

Veiko, Vadim; Karlagina, Yulia; Moskvin, Mikhail; Mikhailovskii, Vladimir; Odintsova, Galina; Olshin, Pavel; Pankin, Dmitry; Romanov, Valery; Yatsuk, Roman

2017-09-01

In this work, we studied a method of laser-induced coloration of metals, where small-scale spatially periodic structures play a key role in the process of color formation. The formation of such structures on a surface of AISI 304 stainless steel was demonstrated for the 1.06 μm fiber laser with nanosecond duration of pulses and random (elliptical) polarization. The color of the surface depends on the period, height and orientation of periodic surface structures. Adjustment of the polarization of the laser radiation or change of laser incidence angle can be used to control the orientation of the structures. The formation of markings that change their color under the different viewing angles becomes possible. The potential application of the method is metal product protection against falsification.

FAST satellite observations of large-amplitude solitary structures

NASA Astrophysics Data System (ADS)

Ergun, R. E.; Carlson, C. W.; McFadden, J. P.; Mozer, F. S.; Delory, G. T.; Peria, W.; Chaston, C. C.; Temerin, M.; Roth, I.; Muschietti, L.; Elphic, R.; Strangeway, R.; Pfaff, R.; Cattell, C. A.; Klumpar, D.; Shelley, E.; Peterson, W.; Moebius, E.; Kistler, L.

We report observations of “fast solitary waves” that are ubiquitous in downward current regions of the mid-altitude auroral zone. The single-period structures have large amplitudes (up to 2.5 V/m), travel much faster than the ion acoustic speed, carry substantial potentials (up to ∼100 Volts), and are associated with strong modulations of energetic electron fluxes. The amplitude and speed of the structures distinguishes them from ion-acoustic solitary waves or weak double layers. The electromagnetic signature appears to be that of an positive charge (electron hole) traveling anti-earthward. We present evidence that the structures are in or near regions of magnetic-field-aligned electric fields and propose that these nonlinear structures play a key role in supporting parallel electric fields in the downward current region of the auroral zone.

Molecular characterization and mRNA expression of two key enzymes of hypoxia-sensing pathways in eastern oysters Crassostrea virginica (Gmelin): Hypoxia-inducible factor α (HIF-α) and HIF-prolyl hydroxylase (PHD)

PubMed Central

Piontkivska, Helen; Chung, J. Sook; Ivanina, Anna V.; Sokolov, Eugene P.; Techa, Sirinart; Sokolova, Inna M.

2010-01-01

Oxygen homeostasis is crucial for development, survival and normal function of all metazoans. A family of transcription factors called hypoxia-inducible factors (HIF) is critical in mediating the adaptive responses to reduced oxygen availability. The HIF transcription factor consists of a constitutively expressed β subunit and an oxygen-dependent α subunit; the abundance of the latter determines the activity of HIF and is regulated by a family of O2- and Fe2+-dependent enzymes prolyl hydroxylases (PHDs). Currently very little is known about the function of this important pathway and the molecular structure of its key players in hypoxia-tolerant intertidal mollusks including oysters, which are among the animal champions of anoxic and hypoxic tolerance and thus can serve as excellent models to study the role of HIF cascade in adaptations to oxygen deficiency. We have isolated transcripts of two key components of the oxygen sensing pathway - the oxygen-regulated HIF-α subunit and PHD - from an intertidal mollusk, the eastern oyster Crassostrea virginica, and determined the transcriptional responses of these two genes to anoxia, hypoxia and cadmium (Cd) stress. HIF-α and PHD homologs from eastern oysters C. virginica show significant sequence similarity and share key functional domains with the earlier described isoforms from vertebrates and invertebrates. Phylogenetic analysis shows that genetic diversification of HIF and PHD isoforms occurred within the vertebrate lineage indicating functional diversification and specialization of the oxygen-sensing pathways in this group, which parallels situation observed for many other important genes. HIF-α and PHD homologs are broadly expressed at the mRNA level in different oyster tissues and show transcriptional responses to prolonged hypoxia in the gills consistent with their putative role in oxygen sensing and the adaptive response to hypoxia. Similarity in amino acid sequence, domain structure and transcriptional responses between HIF-α and PHD homologs from oysters and other invertebrate and vertebrate species implies the highly conserved functions of these genes throughout the evolutionary history of animals, in accordance with their critical role in oxygen sensing and homeostasis. PMID:21106446

The organisational and human resource challenges facing primary care trusts: protocol of a multiple case study

PubMed Central

2001-01-01

Background The study is designed to assess the organisational and human resource challenges faced by Primary Care Trusts (PCTs). Its objectives are to: specify the organisational and human resources challenges faced by PCTs in fulfilling the roles envisaged in government and local policy; examine how PCTs are addressing these challenges, in particular, to describe the organisational forms they have adopted, and the OD/HR strategies and initiatives they have planned or in place; assess how effective these structures, strategies and initiatives have been in enabling the PCTs to meet the organisational and human resources challenges they face; identify the factors, both internal to the PCT and in the wider health community, which have contributed to the success or failure of different structures, strategies and initiatives. Methods The study will be undertaken in three stages. In Stage 1 the key literature on public sector and NHS organisational development and human resources management will be reviewed, and discussions will be held with key researchers and policy makers working in this area. Stage 2 will focus on detailed case studies in six PCTs designed to examine the organisational and human resources challenges they face. Data will be collected using semi-structured interviews, group discussion, site visits, observation of key meetings and examination of local documentation. The findings from the case study PCTs will be cross checked with a Reference Group of up to 20 other PCG/Ts, and key officers working in organisational development or primary care at local, regional and national level. In Stage 3 analysis of findings from the preparatory work, the case studies and the feedback from the Reference Group will be used to identify practical lessons for PCTs, key messages for policy makers, and contributions to further theoretical development. PMID:11737883

Nuclear pore complex integrity requires Lnp1, a regulator of cortical endoplasmic reticulum

PubMed Central

Casey, Amanda K.; Chen, Shuliang; Novick, Peter; Ferro-Novick, Susan; Wente, Susan R.

2015-01-01

The nuclear envelope (NE) and endoplasmic reticulum (ER) are components of the same contiguous membrane system and yet have distinct cellular functions. Mounting evidence suggests roles for some ER proteins in the NE for proper nuclear pore complex (NPC) structure and function. In this study, we identify a NE role in Saccharomyces cerevisiae for Lnp1 and Sey1, proteins required for proper cortical ER formation. Both lnp1Δ and sey1Δ mutants exhibit synthetic genetic interactions with mutants in genes encoding key NPC structural components. Both Lnp1 and Sey1 physically associate with other ER components that have established NPC roles, including Rtn1, Yop1, Pom33, and Per33. Of interest, lnp1Δ rtn1Δ mutants but not rtn1Δ sey1Δ mutants exhibit defects in NPC distribution. Furthermore, the essential NPC assembly factor Ndc1 has altered interactions in the absence of Sey1. Lnp1 dimerizes in vitro via its C-terminal zinc finger motif, a property that is required for proper ER structure but not NPC integrity. These findings suggest that Lnp1's role in NPC integrity is separable from functions in the ER and is linked to Ndc1 and Rtn1 interactions. PMID:26041935

Key diffusion mechanisms involved in regulating bidirectional water permeation across E. coli outer membrane lectin

PubMed Central

Sachdeva, Shivangi; Kolimi, Narendar; Nair, Sanjana Anilkumar; Rathinavelan, Thenmalarchelvi

2016-01-01

Capsular polysaccharides (CPSs) are major bacterial virulent determinants that facilitate host immune evasion. E. coli group1 K30CPS is noncovalently attached to bacterial surface by Wzi, a lectin. Intriguingly, structure based phylogenetic analysis indicates that Wzi falls into porin superfamily. Molecular dynamics (MD) simulations further shed light on dual role of Wzi as it also functions as a bidirectional passive water specific porin. Such a functional role of Wzi was not realized earlier, due to the occluded pore. While five water specific entry points distributed across extracellular & periplasmic faces regulate the water diffusion involving different mechanisms, a luminal hydrophobic plug governs water permeation across the channel. Coincidently, MD observed open state structure of “YQF” triad is seen in sugar-binding site of sodium-galactose cotransporters, implicating its involvement in K30CPS surface anchorage. Importance of Loop 5 (L5) in membrane insertion is yet another highlight. Change in water diffusion pattern of periplasmic substitution mutants suggests Wzi’s role in osmoregulation by aiding in K30CPS hydration, corroborating earlier functional studies. Water molecules located inside β-barrel of Wzi crystal structure further strengthens the role of Wzi in osmoregulation. Thus, interrupting water diffusion or L5 insertion may reduce bacterial virulence. PMID:27320406

Improved workflow modelling using role activity diagram-based modelling with application to a radiology service case study.

PubMed

Shukla, Nagesh; Keast, John E; Ceglarek, Darek

2014-10-01

The modelling of complex workflows is an important problem-solving technique within healthcare settings. However, currently most of the workflow models use a simplified flow chart of patient flow obtained using on-site observations, group-based debates and brainstorming sessions, together with historic patient data. This paper presents a systematic and semi-automatic methodology for knowledge acquisition with detailed process representation using sequential interviews of people in the key roles involved in the service delivery process. The proposed methodology allows the modelling of roles, interactions, actions, and decisions involved in the service delivery process. This approach is based on protocol generation and analysis techniques such as: (i) initial protocol generation based on qualitative interviews of radiology staff, (ii) extraction of key features of the service delivery process, (iii) discovering the relationships among the key features extracted, and, (iv) a graphical representation of the final structured model of the service delivery process. The methodology is demonstrated through a case study of a magnetic resonance (MR) scanning service-delivery process in the radiology department of a large hospital. A set of guidelines is also presented in this paper to visually analyze the resulting process model for identifying process vulnerabilities. A comparative analysis of different workflow models is also conducted. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chapter C. The Loma Prieta, California, Earthquake of October 17, 1989 - Building Structures

USGS Publications Warehouse

Çelebi, Mehmet

1998-01-01

Several approaches are used to assess the performance of the built environment following an earthquake -- preliminary damage surveys conducted by professionals, detailed studies of individual structures, and statistical analyses of groups of structures. Reports of damage that are issued by many organizations immediately following an earthquake play a key role in directing subsequent detailed investigations. Detailed studies of individual structures and statistical analyses of groups of structures may be motivated by particularly good or bad performance during an earthquake. Beyond this, practicing engineers typically perform stress analyses to assess the performance of a particular structure to vibrational levels experienced during an earthquake. The levels may be determined from recorded or estimated ground motions; actual levels usually differ from design levels. If a structure has seismic instrumentation to record response data, the estimated and recorded response and behavior of the structure can be compared.

I-motif DNA structures are formed in the nuclei of human cells

NASA Astrophysics Data System (ADS)

Zeraati, Mahdi; Langley, David B.; Schofield, Peter; Moye, Aaron L.; Rouet, Romain; Hughes, William E.; Bryan, Tracy M.; Dinger, Marcel E.; Christ, Daniel

2018-06-01

Human genome function is underpinned by the primary storage of genetic information in canonical B-form DNA, with a second layer of DNA structure providing regulatory control. I-motif structures are thought to form in cytosine-rich regions of the genome and to have regulatory functions; however, in vivo evidence for the existence of such structures has so far remained elusive. Here we report the generation and characterization of an antibody fragment (iMab) that recognizes i-motif structures with high selectivity and affinity, enabling the detection of i-motifs in the nuclei of human cells. We demonstrate that the in vivo formation of such structures is cell-cycle and pH dependent. Furthermore, we provide evidence that i-motif structures are formed in regulatory regions of the human genome, including promoters and telomeric regions. Our results support the notion that i-motif structures provide key regulatory roles in the genome.

Computational methods for constructing protein structure models from 3D electron microscopy maps.

PubMed

Esquivel-Rodríguez, Juan; Kihara, Daisuke

2013-10-01

Protein structure determination by cryo-electron microscopy (EM) has made significant progress in the past decades. Resolutions of EM maps have been improving as evidenced by recently reported structures that are solved at high resolutions close to 3Å. Computational methods play a key role in interpreting EM data. Among many computational procedures applied to an EM map to obtain protein structure information, in this article we focus on reviewing computational methods that model protein three-dimensional (3D) structures from a 3D EM density map that is constructed from two-dimensional (2D) maps. The computational methods we discuss range from de novo methods, which identify structural elements in an EM map, to structure fitting methods, where known high resolution structures are fit into a low-resolution EM map. A list of available computational tools is also provided. Copyright © 2013 Elsevier Inc. All rights reserved.

Apolipoprotein AI tertiary structures determine stability and phospholipid-binding activity of discoidal high-density lipoprotein particles of different sizes

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

Chen, Bin; Ren, Xuefeng; Neville, Tracey

2009-05-18

Human high-density lipoprotein (HDL) plays a key role in the reverse cholesterol transport pathway that delivers excess cholesterol back to the liver for clearance. In vivo, HDL particles vary in size, shape and biological function. The discoidal HDL is a 140-240 kDa, disk-shaped intermediate of mature HDL. During mature spherical HDL formation, discoidal HDLs play a key role in loading cholesterol ester onto the HDL particles by activating the enzyme, lecithin:cholesterol acyltransferase (LCAT). One of the major problems for high-resolution structural studies of discoidal HDL is the difficulty in obtaining pure and, foremost, homogenous sample. We demonstrate here that themore » commonly used cholate dialysis method for discoidal HDL preparation usually contains 5-10% lipid-poor apoAI that significantly interferes with the high-resolution structural analysis of discoidal HDL using biophysical methods. Using an ultracentrifugation method, we quickly removed lipid-poor apoAI. We also purified discoidal reconstituted HDL (rHDL) into two pure discoidal HDL species of different sizes that are amendable for high-resolution structural studies. A small rHDL has a diameter of 7.6 nm, and a large rHDL has a diameter of 9.8 nm. We show that these two different sizes of discoidal HDL particles display different stability and phospholipid-binding activity. Interestingly, these property/functional differences are independent from the apoAI -helical secondary structure, but are determined by the tertiary structural difference of apoAI on different discoidal rHDL particles, as evidenced by two-dimensional NMR and negative stain electron microscopy data. Our result further provides the first high-resolution NMR data, demonstrating a promise of structural determination of discoidal HDL at atomic resolution using a combination of NMR and other biophysical techniques.« less

Biological functions of proline in morphogenesis and osmotolerance revealed in antisense transgenic Arabidopsis thaliana.

PubMed

Nanjo, T; Kobayashi, M; Yoshiba, Y; Sanada, Y; Wada, K; Tsukaya, H; Kakubari, Y; Yamaguchi-Shinozaki, K; Shinozaki, K

1999-04-01

Many organisms, including higher plants, accumulate free proline (Pro) in response to osmotic stress. Although various studies have focused on the ability of Pro as a compatible osmolyte involved in osmotolerance, its specific role throughout plant growth is still unclear. It has been reported that Pro is synthesized from Glu catalyzed by a key enzyme, delta 1-pyrroline-5-carboxylate synthetase (P5CS), in plants. To elucidate essential roles of Pro, we generated antisense transgenic Arabidopsis plants with a P5CS cDNA. Several transgenics accumulated Pro at a significantly lower level than wild-type plants, providing direct evidence for a key role of P5CS in Pro production in Arabidopsis. These antisense transgenics showed morphological alterations in leaves and a defect in elongation of inflorescences. Furthermore, transgenic leaves were hypersensitive to osmotic stress. Microscopic analysis of transgenic leaves, in which the mutated phenotype clearly occurred, showed morphological abnormalities of epidermal and parenchymatous cells and retardation of differentiation of vascular systems. These phenotypes were suppressed by exogenous L-Pro but not by D-Pro or other Pro analogues. In addition, Pro deficiency did not broadly affect all proteins but specifically affected structural proteins of cell walls in the antisense transgenic plants. These results indicate that Pro is not just an osmoregulator in stressed plants but has a unique function involved in osmotolerance as well as in morphogenesis as a major constituent of cell wall structural proteins in plants.

Using Social Network Analysis to Examine the Effect of Care Management Structure on Chronic Disease Management Communication Within Primary Care.

PubMed

Holtrop, Jodi Summers; Ruland, Sandra; Diaz, Stephanie; Morrato, Elaine H; Jones, Eric

2018-05-01

Care management and care managers are becoming increasingly prevalent in primary care medical practice as a means of improving population health and reducing unnecessary care. Care managers are often involved in chronic disease management and associated transitional care. In this study, we examined the communication regarding chronic disease care within 24 primary care practices in Michigan and Colorado. We sought to answer the following questions: Do care managers play a key role in chronic disease management in the practice? Does the prominence of the care manager's connectivity within the practice's communication network vary by the type of care management structure implemented? Individual written surveys were given to all practice members in the participating practices. Survey questions assessed demographics as well as practice culture, quality improvement, care management activities, and communication regarding chronic disease care. Using social network analysis and other statistical methods, we analyzed the communication dynamics related to chronic disease care for each practice. The structure of chronic disease communication varies greatly from practice to practice. Care managers who were embedded in the practice or co-located were more likely to be in the core of the communication network than were off-site care managers. These care managers also had higher in-degree centrality, indicating that they acted as a hub for communication with team members in many other roles. Social network analysis provided a useful means of examining chronic disease communication in practice, and highlighted the central role of care managers in this communication when their role structure supported such communication. Structuring care managers as embedded team members within the practice has important implications for their role in chronic disease communication within primary care.

Distinct spinning patterns gain differentiated loading tolerance of silk thread anchorages in spiders with different ecology.

PubMed

Wolff, Jonas O; van der Meijden, Arie; Herberstein, Marie E

2017-07-26

Building behaviour in animals extends biological functions beyond bodies. Many studies have emphasized the role of behavioural programmes, physiology and extrinsic factors for the structure and function of buildings. Structure attachments associated with animal constructions offer yet unrealized research opportunities. Spiders build a variety of one- to three-dimensional structures from silk fibres. The evolution of economic web shapes as a key for ecological success in spiders has been related to the emergence of high performance silks and thread coating glues. However, the role of thread anchorages has been widely neglected in those models. Here, we show that orb-web (Araneidae) and hunting spiders (Sparassidae) use different silk application patterns that determine the structure and robustness of the joint in silk thread anchorages. Silk anchorages of orb-web spiders show a greater robustness against different loading situations, whereas the silk anchorages of hunting spiders have their highest pull-off resistance when loaded parallel to the substrate along the direction of dragline spinning. This suggests that the behavioural 'printing' of silk into attachment discs along with spinneret morphology was a prerequisite for the evolution of extended silk use in a three-dimensional space. This highlights the ecological role of attachments in the evolution of animal architectures. © 2017 The Author(s).

Presence of extracellular DNA in the Candida albicans biofilm matrix and its contribution to biofilms.

PubMed

Martins, Margarida; Uppuluri, Priya; Thomas, Derek P; Cleary, Ian A; Henriques, Mariana; Lopez-Ribot, José L; Oliveira, Rosário

2010-05-01

DNA has been described as a structural component of the extracellular matrix (ECM) in bacterial biofilms. In Candida albicans, there is a scarce knowledge concerning the contribution of extracellular DNA (eDNA) to biofilm matrix and overall structure. This work examined the presence and quantified the amount of eDNA in C. albicans biofilm ECM and the effect of DNase treatment and the addition of exogenous DNA on C. albicans biofilm development as indicators of a role for eDNA in biofilm development. We were able to detect the accumulation of eDNA in biofilm ECM extracted from C. albicans biofilms formed under conditions of flow, although the quantity of eDNA detected differed according to growth conditions, in particular with regards to the medium used to grow the biofilms. Experiments with C. albicans biofilms formed statically using a microtiter plate model indicated that the addition of exogenous DNA (>160 ng/ml) increases biofilm biomass and, conversely, DNase treatment (>0.03 mg/ml) decreases biofilm biomass at later time points of biofilm development. We present evidence for the role of eDNA in C. albicans biofilm structure and formation, consistent with eDNA being a key element of the ECM in mature C. albicans biofilms and playing a predominant role in biofilm structural integrity and maintenance.

The role of the charge nurse manager: a descriptive exploratory study.

PubMed

McCallin, A M; Frankson, C

2010-04-01

To explore the charge nurse manager role. Management in nursing is increasingly challenging. Restructuring of organizations has had an impact on the scope of the charge nurse manager role that has expanded so that managers are now expected to be leaders. If role preparation is inadequate, potential for role confusion and role stress increases, undermining role effectiveness in this key senior nursing position. This descriptive exploratory study investigated the experiences of charge nurse managers. Twelve nurse managers from an acute care hospital in New Zealand were interviewed. Data were analysed thematically. Three themes, role ambiguity, business management deficit and role overload emerged. It was evident that charge nurse managers were appointed into a management role with clinical expertise but without management skills. Findings suggest that role preparation should include postgraduate education and business management training. Role induction requires a formal organizational management trainee programme and ongoing supportive clinical supervision. New approaches to charge nurse manager role development are needed. Organizations must provide formal structural support to facilitate management development. The profession needs to promote succession planning that would reduce these longstanding problems.

The structure and function of the dopamine transporter and its role in CNS diseases.

PubMed

McHugh, Patrick C; Buckley, David A

2015-01-01

In this chapter, we explore the basic science of the dopamine transporter (DAT), an integral component of a system that regulates dopamine homeostasis. Dopamine is a key neurotransmitter for several brain functions including locomotor control and reward systems. The transporter structure, function, mechanism of action, localization, and distribution, in addition to gene regulation, are discussed. Over many years, a wealth of information concerning the DAT has been accrued and has led to increased interest in the role of the DAT in a plethora of central nervous system diseases. These DAT characteristics are explored in relation to a range of neurological and neuropsychiatric diseases, with a particular focus on the genetics of the DAT. In addition, we discuss the pharmacology of the DAT and how this relates to disease and addiction. © 2015 Elsevier Inc. All rights reserved.

Coevolution of yeast mannan digestion: Convergence of the civilized human diet, distal gut microbiome, and host immunity

PubMed Central

Abbott, D Wade; Martens, Eric C; Gilbert, Harry J; Cuskin, Fiona; Lowe, Elisabeth C

2015-01-01

The complex carbohydrates accessible to the distal gut microbiota (DGM) are key drivers in determining the structure of this ecosystem. Typically, plant cell wall polysaccharides and recalcitrant starch (i.e. dietary fiber), in addition to host glycans are considered the primary nutrients for the DGM; however, we recently demonstrated that α-mannans, highly branched polysaccharides that decorate the surface of yeast, are also nutrients for several members of Bacteroides spp. This relationship suggests that the advent of yeast in contemporary food technologies and the colonization of the intestine by endogenous fungi have roles in microbiome structure and function. Here we discuss the process of yeast mannan metabolism, and the intersection between various sources of intestinal fungi and their roles in recognition by the host innate immune system. PMID:26440374

Revealing the distinct folding phases of an RNA three-helix junction.

PubMed

Plumridge, Alex; Katz, Andrea M; Calvey, George D; Elber, Ron; Kirmizialtin, Serdal; Pollack, Lois

2018-05-14

Remarkable new insight has emerged into the biological role of RNA in cells. RNA folding and dynamics enable many of these newly discovered functions, calling for an understanding of RNA self-assembly and conformational dynamics. Because RNAs pass through multiple structures as they fold, an ensemble perspective is required to visualize the flow through fleetingly populated sets of states. Here, we combine microfluidic mixing technology and small angle X-ray scattering (SAXS) to measure the Mg-induced folding of a small RNA domain, the tP5abc three helix junction. Our measurements are interpreted using ensemble optimization to select atomically detailed structures that recapitulate each experimental curve. Structural ensembles, derived at key stages in both time-resolved studies and equilibrium titrations, reproduce the features of known intermediates, and more importantly, offer a powerful new structural perspective on the time-progression of folding. Distinct collapse phases along the pathway appear to be orchestrated by specific interactions with Mg ions. These key interactions subsequently direct motions of the backbone that position the partners of tertiary contacts for later bonding, and demonstrate a remarkable synergy between Mg and RNA across numerous time-scales.

Structure of Yeast OSBP-Related Protein Osh1 Reveals Key Determinants for Lipid Transport and Protein Targeting at the Nucleus-Vacuole Junction.

PubMed

Manik, Mohammad Kawsar; Yang, Huiseon; Tong, Junsen; Im, Young Jun

2017-04-04

Yeast Osh1 belongs to the oxysterol-binding protein (OSBP) family of proteins and contains multiple targeting modules optimized for lipid transport at the nucleus-vacuole junction (NVJ). The key determinants for NVJ targeting and the role of Osh1 at NVJs have remained elusive because of unknown lipid specificities. In this study, we determined the structures of the ankyrin repeat domain (ANK), and OSBP-related domain (ORD) of Osh1, in complex with Nvj1 and ergosterol, respectively. The Osh1 ANK forms a unique bi-lobed structure that recognizes a cytosolic helical segment of Nvj1. We discovered that Osh1 ORD binds ergosterol and phosphatidylinositol 4-phosphate PI(4)P in a competitive manner, suggesting counter-transport function of the two lipids. Ergosterol is bound to the hydrophobic pocket in a head-down orientation, and the structure of the PI(4)P-binding site in Osh1 is well conserved. Our results suggest that Osh1 performs non-vesicular transport of ergosterol and PI(4)P at the NVJ. Copyright © 2017 Elsevier Ltd. All rights reserved.

Insights into Substrate Specificity and Metal Activation of Mammalian Tetrahedral Aspartyl Aminopeptidase*

PubMed Central

Chen, Yuanyuan; Farquhar, Erik R.; Chance, Mark R.; Palczewski, Krzysztof; Kiser, Philip D.

2012-01-01

Aminopeptidases are key enzymes involved in the regulation of signaling peptide activity. Here, we present a detailed biochemical and structural analysis of an evolutionary highly conserved aspartyl aminopeptidase called DNPEP. We show that this peptidase can cleave multiple physiologically relevant substrates, including angiotensins, and thus may play a key role in regulating neuron function. Using a combination of x-ray crystallography, x-ray absorption spectroscopy, and single particle electron microscopy analysis, we provide the first detailed structural analysis of DNPEP. We show that this enzyme possesses a binuclear zinc-active site in which one of the zinc ions is readily exchangeable with other divalent cations such as manganese, which strongly stimulates the enzymatic activity of the protein. The plasticity of this metal-binding site suggests a mechanism for regulation of DNPEP activity. We also demonstrate that DNPEP assembles into a functionally relevant tetrahedral complex that restricts access of peptide substrates to the active site. These structural data allow rationalization of the enzyme's preference for short peptide substrates with N-terminal acidic residues. This study provides a structural basis for understanding the physiology and bioinorganic chemistry of DNPEP and other M18 family aminopeptidases. PMID:22356908

Biophysical analysis of the effect of chemical modification by 4-oxononenal on the structure, stability, and function of binding immunoglobulin protein (BiP)

PubMed Central

Shah, Dinen D.; Singh, Surinder M.; Dzieciatkowska, Monika

2017-01-01

Binding immunoglobulin protein (BiP) is a molecular chaperone important for the folding of numerous proteins, which include millions of immunoglobulins in human body. It also plays a key role in the unfolded protein response (UPR) in the endoplasmic reticulum. Free radical generation is a common phenomenon that occurs in cells under healthy as well as under stress conditions such as ageing, inflammation, alcohol consumption, and smoking. These free radicals attack the cell membranes and generate highly reactive lipid peroxidation products such as 4-oxononenal (4-ONE). BiP is a key protein that is modified by 4-ONE. In this study, we probed how such chemical modification affects the biophysical properties of BiP. Upon modification, BiP shows significant tertiary structural changes with no changes in its secondary structure. The protein loses its thermodynamic stability, particularly, that of the nucleotide binding domain (NBD) where ATP binds. In terms of function, the modified BiP completely loses its ATPase activity with decreased ATP binding affinity. However, modified BiP retains its immunoglobulin binding function and its chaperone activity of suppressing non-specific protein aggregation. These results indicate that 4-ONE modification can significantly affect the structure-function of key proteins such as BiP involved in cellular pathways, and provide a molecular basis for how chemical modifications can result in the failure of quality control mechanisms inside the cell. PMID:28886061

Fluoride-Mediated Capture of a Noncovalent Bound State of a Reversible Covalent Enzyme Inhibitor: X-ray Crystallographic Analysis of an Exceptionally Potent [alpha]-Ketoheterocycle Inhibitor of Fatty Acid Amide Hydrolase

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

Mileni, Mauro; Garfunkle, Joie; Ezzili, Cyrine

2011-11-02

Two cocrystal X-ray structures of the exceptionally potent {alpha}-ketoheterocycle inhibitor 1 (K{sub i} = 290 pM) bound to a humanized variant of rat fatty acid amide hydrolase (FAAH) are disclosed, representing noncovalently and covalently bound states of the same inhibitor with the enzyme. Key to securing the structure of the noncovalently bound state of the inhibitor was the inclusion of fluoride ion in the crystallization conditions that is proposed to bind the oxyanion hole precluding inhibitor covalent adduct formation with stabilization of the tetrahedral hemiketal. This permitted the opportunity to detect important noncovalent interactions stabilizing the binding of the inhibitormore » within the FAAH active site independent of the covalent reaction. Remarkably, noncovalently bound 1 in the presence of fluoride appears to capture the active site in the same 'in action' state with the three catalytic residues Ser241-Ser217-Lys142 occupying essentially identical positions observed in the covalently bound structure of 1, suggesting that this technique of introducing fluoride may have important applications in structural studies beyond inhibiting substrate or inhibitor oxyanion hole binding. Key insights to emerge from the studies include the observations that noncovalently bound 1 binds in its ketone (not gem diol) form, that the terminal phenyl group in the acyl side chain of the inhibitor serves as the key anchoring interaction overriding the intricate polar interactions in the cytosolic port, and that the role of the central activating heterocycle is dominated by its intrinsic electron-withdrawing properties. These two structures are also briefly compared with five X-ray structures of {alpha}-ketoheterocycle-based inhibitors bound to FAAH recently disclosed.« less

The impact of hospital structure and restructuring on the nursing workforce.

PubMed

Duffield, Christine; Kearin, Mark; Johnston, Judy; Leonard, Joanna

2007-01-01

Health systems throughout much of the world have been subject to 'reform' in recent years as countries have attempted to contain the rapidly rising costs of health care. Changes to hospital structures (restructuring) have been an important part of these reforms. A significant impact of current approaches to restructuring is the loss of, or changes to, nursing management roles and functions. Australian hospitals Little evaluation has been undertaken to determine the impact of hospital structure and organisational restructuring on the nursing workforce. There is some indication that nurses have experienced a loss of key management positions, which may impact on their capacity to ensure that adequate and safe care is provided at the ward level.

Perceived role and its enhancing factors among the village health volunteers regarding malaria control in rural myanmar.

PubMed

Aung, P Linn; Silawan, Tassanee; Rawiworrakul, Tassanee; Min, Myo

2018-01-01

Village health volunteers (VHVs) are key agents for malaria control in community. The Myanmar Medical Association-Malaria (MMA-Malaria) Project has promoted effective malaria control in endemic and high-risk townships by supporting roles of VHVs. To assess the roles of VHVs on malaria control and factors enhancing their roles in rural Myanmar. A cross-sectional study was conducted in five townships where the MMA-Malaria Project has been implemented. One hundred and fifty VHVs were sampled from five townships by simple random sampling. Data were collected by trained interviewers using structured questionnaires, which covered sociodemographic, supportive, motivational factors, and roles of malaria control. Studied variables were described by proportions, means, and standard deviations and were analyzed for their association by odds ratio with 95% confidence interval and Chi-square tests. Most of VHVs (96%) expected to demonstrate good roles on malaria control, but only 44.0% exhibited current roles at a good level. Factors enhancing their roles were female (P = 0.037), family income ≥50,001 kyat/month (P < 0.015), time serving as a volunteer 1-2 years (P = 0.006), good knowledge of malaria control (P < 0.001), good family support (P < 0.001), good community support (P < 0.001), and good motivational factors (P = 0.002). VHVs are key agents for malaria control in community. Most of VHVs expected to demonstrate good roles on malaria control, but less than half of them exhibited current roles at a good level. The systems and program for improving VHVs' knowledge, encouraging family and community support, and promoting motivation are essential for their better roles.

Sequence and Structure Dependent DNA-DNA Interactions

NASA Astrophysics Data System (ADS)

Kopchick, Benjamin; Qiu, Xiangyun

Molecular forces between dsDNA strands are largely dominated by electrostatics and have been extensively studied. Quantitative knowledge has been accumulated on how DNA-DNA interactions are modulated by varied biological constituents such as ions, cationic ligands, and proteins. Despite its central role in biology, the sequence of DNA has not received substantial attention and ``random'' DNA sequences are typically used in biophysical studies. However, ~50% of human genome is composed of non-random-sequence DNAs, particularly repetitive sequences. Furthermore, covalent modifications of DNA such as methylation play key roles in gene functions. Such DNAs with specific sequences or modifications often take on structures other than the canonical B-form. Here we present series of quantitative measurements of the DNA-DNA forces with the osmotic stress method on different DNA sequences, from short repeats to the most frequent sequences in genome, and to modifications such as bromination and methylation. We observe peculiar behaviors that appear to be strongly correlated with the incurred structural changes. We speculate the causalities in terms of the differences in hydration shell and DNA surface structures.

Common electronic origin of superconductivity in (Li,Fe)OHFeSe bulk superconductor and single-layer FeSe/SrTiO3 films.

PubMed

Zhao, Lin; Liang, Aiji; Yuan, Dongna; Hu, Yong; Liu, Defa; Huang, Jianwei; He, Shaolong; Shen, Bing; Xu, Yu; Liu, Xu; Yu, Li; Liu, Guodong; Zhou, Huaxue; Huang, Yulong; Dong, Xiaoli; Zhou, Fang; Liu, Kai; Lu, Zhongyi; Zhao, Zhongxian; Chen, Chuangtian; Xu, Zuyan; Zhou, X J

2016-02-08

The mechanism of high-temperature superconductivity in the iron-based superconductors remains an outstanding issue in condensed matter physics. The electronic structure plays an essential role in dictating superconductivity. Recent revelation of distinct electronic structure and high-temperature superconductivity in the single-layer FeSe/SrTiO3 films provides key information on the role of Fermi surface topology and interface in inducing or enhancing superconductivity. Here we report high-resolution angle-resolved photoemission measurements on the electronic structure and superconducting gap of an FeSe-based superconductor, (Li0.84Fe0.16)OHFe0.98Se, with a Tc at 41 K. We find that this single-phase bulk superconductor shows remarkably similar electronic behaviours to that of the superconducting single-layer FeSe/SrTiO3 films in terms of Fermi surface topology, band structure and the gap symmetry. These observations provide new insights in understanding high-temperature superconductivity in the single-layer FeSe/SrTiO3 films and the mechanism of superconductivity in the bulk iron-based superconductors.

The Solution Structure, Binding Properties, and Dynamics of the Bacterial Siderophore-binding Protein FepB*

PubMed Central

Chu, Byron C. H.; Otten, Renee; Krewulak, Karla D.; Mulder, Frans A. A.; Vogel, Hans J.

2014-01-01

The periplasmic binding protein (PBP) FepB plays a key role in transporting the catecholate siderophore ferric enterobactin from the outer to the inner membrane in Gram-negative bacteria. The solution structures of the 34-kDa apo- and holo-FepB from Escherichia coli, solved by NMR, represent the first solution structures determined for the type III class of PBPs. Unlike type I and II PBPs, which undergo large “Venus flytrap” conformational changes upon ligand binding, both forms of FepB maintain similar overall folds; however, binding of the ligand is accompanied by significant loop movements. Reverse methyl cross-saturation experiments corroborated chemical shift perturbation results and uniquely defined the binding pocket for gallium enterobactin (GaEnt). NMR relaxation experiments indicated that a flexible loop (residues 225–250) adopted a more rigid and extended conformation upon ligand binding, which positioned residues for optimal interactions with the ligand and the cytoplasmic membrane ABC transporter (FepCD), respectively. In conclusion, this work highlights the pivotal role that structural dynamics plays in ligand binding and transporter interactions in type III PBPs. PMID:25173704

The role of strong electrostatic interactions at the dimer interface of human glutathione synthetase.

PubMed

De Jesus, Margarita C; Ingle, Brandall L; Barakat, Khaldoon A; Shrestha, Bisesh; Slavens, Kerri D; Cundari, Thomas R; Anderson, Mary E

2014-10-01

The obligate homodimer human glutathione synthetase (hGS) provides an ideal system for exploring the role of protein-protein interactions in the structural stability, activity and allostery of enzymes. The two active sites of hGS, which are 40 Å apart, display allosteric modulation by the substrate γ-glutamylcysteine (γ-GC) during the synthesis of glutathione, a key cellular antioxidant. The two subunits interact at a relatively small dimer interface dominated by electrostatic interactions between S42, R221, and D24. Alanine scans of these sites result in enzymes with decreased activity, altered γ-GC affinity, and decreased thermal stability. Molecular dynamics simulations indicate these mutations disrupt interchain bonding and impact the tertiary structure of hGS. While the ionic hydrogen bonds and salt bridges between S42, R221, and D24 do not mediate allosteric communication in hGS, these interactions have a dramatic impact on the activity and structural stability of the enzyme.

Origin of the energy level alignment at organic/organic interfaces: The role of structural defects

NASA Astrophysics Data System (ADS)

Bussolotti, Fabio; Yang, Jinpeng; Hinderhofer, Alexander; Huang, Yuli; Chen, Wei; Kera, Satoshi; Wee, Andrew T. S.; Ueno, Nobuo

2014-03-01

In this paper, the electronic properties of as-deposited and N2-exposedCuPc/F16CuPc interface, a prototype system for organic photovoltaic applications, are investigated by using ultralow background, high-sensitivity photoemission spectroscopy. It is found that (i) N2 exposure significantly modifies the energy level alignment (ELA) at the interface between CuPc and F16CuPc layer and (ii) the direction of the N2-induced energy level shift of the CuPc depends on the position of the Fermi level (EF) in the CuPc highest occupied molecular orbital-lowest unoccupied molecular orbital gap of the as-deposited film. These observations are related to the changes in the density of gap states (DOGS) produced by structural imperfections in the molecular packing geometry, as introduced by the N2 penetration into the CuPc layer. This result demonstrates the key role of structure-induced DOGS in controlling the ELA at organic/organic interfaces.

Anti-transgender prejudice: a structural equation model of associated constructs.

PubMed

Tebbe, Esther N; Moradi, Bonnie

2012-04-01

This study aimed to identify theoretically relevant key correlates of anti-transgender prejudice. Specifically, structural equation modeling was used to test the unique relations of anti-lesbian, gay, and bisexual (LGB) prejudice; traditional gender role attitudes; need for closure; and social dominance orientation with anti-transgender prejudice. Social desirability was controlled as a covariate in the model. Analyses of data from 250 undergraduate students indicated that anti-LGB prejudice, traditional gender role attitudes, and need for closure each had positive unique relations with anti-transgender prejudice beyond the negative association of social desirability with such prejudice. By contrast, social dominance orientation was not related uniquely to anti-transgender prejudice. Additional analyses indicated that women's mean level of anti-transgender prejudice was lower than that of men's, but the pattern of relations between the predictor variables and anti-transgender prejudice did not differ between women and men. A confirmatory factor analysis also supported the unidimensional structure of anti-transgender prejudice as operationalized by Nagoshi et al.'s (2008) Transphobia Scale.

A Specific Two-pore Domain Potassium Channel Blocker Defines the Structure of the TASK-1 Open Pore*

PubMed Central

Streit, Anne K.; Netter, Michael F.; Kempf, Franca; Walecki, Magdalena; Rinné, Susanne; Bollepalli, Murali K.; Preisig-Müller, Regina; Renigunta, Vijay; Daut, Jürgen; Baukrowitz, Thomas; Sansom, Mark S. P.; Stansfeld, Phillip J.; Decher, Niels

2011-01-01

Two-pore domain potassium (K2P) channels play a key role in setting the membrane potential of excitable cells. Despite their role as putative targets for drugs and general anesthetics, little is known about the structure and the drug binding site of K2P channels. We describe A1899 as a potent and highly selective blocker of the K2P channel TASK-1. As A1899 acts as an open-channel blocker and binds to residues forming the wall of the central cavity, the drug was used to further our understanding of the channel pore. Using alanine mutagenesis screens, we have identified residues in both pore loops, the M2 and M4 segments, and the halothane response element to form the drug binding site of TASK-1. Our experimental data were used to validate a K2P open-pore homology model of TASK-1, providing structural insights for future rational design of drugs targeting K2P channels. PMID:21362619

Krüppel homolog 1 and E93 mediate Juvenile hormone regulation of metamorphosis in the common bed bug, Cimex lectularius.

PubMed

Gujar, Hemant; Palli, Subba Reddy

2016-05-17

The common bed bug is an obligate hematophagous parasite of humans. We studied the regulation of molting and metamorphosis in bed bugs with a goal to identify key players involved. qRT-PCR studies on the expression of genes known to be involved in molting and metamorphosis showed high levels of Krüppel homolog 1 [Kr-h1, a transcription factor that plays key roles in juvenile hormone (JH) action] mRNA in the penultimate nymphal stage (N4). However, low levels of Kr-h1 mRNA were detected in the fifth and last nymphal stage (N5). Knockdown of Kr-h1 in N4 resulted in a precocious development of adult structures. Kr-h1 maintains the immature stage by suppressing E93 (early ecdysone response gene) in N4. E93 expression increases during the N5 in the absence of Kr-h1 and promotes the development of adult structures. Knockdown of E93 in N5 results in the formation of supernumerary nymphs. The role of JH in the suppression of adult structures through interaction with Kr-h1 and E93 was also studied by the topical application of JH analog, methoprene, to N5. Methoprene induced Kr-h1 and suppressed E93 and induced formation of the supernumerary nymph. These data show interactions between Kr-h1, E93 and JH in the regulation of metamorphosis in the bed bugs.

Krüppel homolog 1 and E93 mediate Juvenile hormone regulation of metamorphosis in the common bed bug, Cimex lectularius

PubMed Central

Gujar, Hemant; Palli, Subba Reddy

2016-01-01

The common bed bug is an obligate hematophagous parasite of humans. We studied the regulation of molting and metamorphosis in bed bugs with a goal to identify key players involved. qRT-PCR studies on the expression of genes known to be involved in molting and metamorphosis showed high levels of Krüppel homolog 1 [Kr-h1, a transcription factor that plays key roles in juvenile hormone (JH) action] mRNA in the penultimate nymphal stage (N4). However, low levels of Kr-h1 mRNA were detected in the fifth and last nymphal stage (N5). Knockdown of Kr-h1 in N4 resulted in a precocious development of adult structures. Kr-h1 maintains the immature stage by suppressing E93 (early ecdysone response gene) in N4. E93 expression increases during the N5 in the absence of Kr-h1 and promotes the development of adult structures. Knockdown of E93 in N5 results in the formation of supernumerary nymphs. The role of JH in the suppression of adult structures through interaction with Kr-h1 and E93 was also studied by the topical application of JH analog, methoprene, to N5. Methoprene induced Kr-h1 and suppressed E93 and induced formation of the supernumerary nymph. These data show interactions between Kr-h1, E93 and JH in the regulation of metamorphosis in the bed bugs. PMID:27185064

Reflectin as a Material for Neural Stem Cell Growth

PubMed Central

2015-01-01

Cephalopods possess remarkable camouflage capabilities, which are enabled by their complex skin structure and sophisticated nervous system. Such unique characteristics have in turn inspired the design of novel functional materials and devices. Within this context, recent studies have focused on investigating the self-assembly, optical, and electrical properties of reflectin, a protein that plays a key role in cephalopod structural coloration. Herein, we report the discovery that reflectin constitutes an effective material for the growth of human neural stem/progenitor cells. Our findings may hold relevance both for understanding cephalopod embryogenesis and for developing improved protein-based bioelectronic devices. PMID:26703760

Further Structural Intelligence for Sensors Cluster Technology in Manufacturing

PubMed Central

Mekid, Samir

2006-01-01

With the ever increasing complex sensing and actuating tasks in manufacturing plants, intelligent sensors cluster in hybrid networks becomes a rapidly expanding area. They play a dominant role in many fields from macro and micro scale. Global object control and the ability to self organize into fault-tolerant and scalable systems are expected for high level applications. In this paper, new structural concepts of intelligent sensors and networks with new intelligent agents are presented. Embedding new functionalities to dynamically manage cooperative agents for autonomous machines are interesting key enabling technologies most required in manufacturing for zero defects production.

Molecular, Cellular, and Structural Mechanisms of Cocaine Addiction: A Key Role for MicroRNAs

PubMed Central

Jonkman, Sietse; Kenny, Paul J

2013-01-01

The rewarding properties of cocaine play a key role in establishing and maintaining the drug-taking habit. However, as exposure to cocaine increases, drug use can transition from controlled to compulsive. Importantly, very little is known about the neurobiological mechanisms that control this switch in drug use that defines addiction. MicroRNAs (miRNAs) are small non-protein coding RNA transcripts that can regulate the expression of messenger RNAs that code for proteins. Because of their highly pleiotropic nature, each miRNA has the potential to regulate hundreds or even thousands of protein-coding RNA transcripts. This property of miRNAs has generated considerable interest in their potential involvement in complex psychiatric disorders such as addiction, as each miRNA could potentially influence the many different molecular and cellular adaptations that arise in response to drug use that are hypothesized to drive the emergence of addiction. Here, we review recent evidence supporting a key role for miRNAs in the ventral striatum in regulating the rewarding and reinforcing properties of cocaine in animals with limited exposure to the drug. Moreover, we discuss evidence suggesting that miRNAs in the dorsal striatum control the escalation of drug intake in rats with extended cocaine access. These findings highlight the central role for miRNAs in drug-induced neuroplasticity in brain reward systems that drive the emergence of compulsive-like drug use in animals, and suggest that a better understanding of how miRNAs control drug intake will provide new insights into the neurobiology of drug addiction. PMID:22968819

Political economy of decentralising HIV and AIDS treatment services to primary healthcare facilities in three Nigerian states.

PubMed

Mbachu, Chinyere; Onwujekwe, Obinna; Ezumah, Nkoli; Ajayi, Olayinka; Sanwo, Olusola; Uzochukwu, Benjamin

2016-09-01

Decentralisation is defined as the dispersion, distribution or transfer of resources, functions and decision-making power from a central authority to regional and local authorities. It is usually accompanied by assignment of accountability and responsibility for results. Fundamental to understanding decentralisation is learning what motivates central governments to give up power and resources to local governments, and the practical significance of this on their positions regarding decentralisation. This study examined key political and institutional influences on role-players' capacity to support decentralisation of HIV and AIDS treatment services to primary healthcare facilities, and implications for sustainability. In-depth interviews were conducted with 55 purposively selected key informants, drawn from three Nigerian states that were at different stages of decentralising HIV and AIDS treatment services to primary care facilities. Key informants represented different categories of role-players involved in HIV and AIDS control programmes. Thematic framework analysis of data was done. Support for decentralisation of HIV and AIDS treatment services to primary healthcare facilities was substantial among different categories of actors. Political factors such as the local and global agenda for health, political tenure and party affiliations, and institutional factors such as consolidation of decision-making power and improvements in career trajectories, influenced role-players support for decentralisation of HIV and AIDS treatment services. It is feasible and acceptable to decentralise HIV and AIDS treatment services to primary healthcare facilities, to help improve coverage. However, role-players' support largely depends on how well the reform aligns with political structures and current institutional practices.

The loop structure and the RNA helicase p72/DDX17 influence the processing efficiency of the mice miR-132

PubMed Central

Remenyi, Judit; Bajan, Sarah; Fuller-Pace, Frances V.; Arthur, J. Simon C.; Hutvagner, Gyorgy

2016-01-01

miRNAs are small RNAs that are key regulators of gene expression in eukaryotic organisms. The processing of miRNAs is regulated by structural characteristics of the RNA and is also tightly controlled by auxiliary protein factors. Among them, RNA binding proteins play crucial roles to facilitate or inhibit miRNA maturation and can be controlled in a cell, tissue and species-specific manners or in response to environmental stimuli. In this study we dissect the molecular mechanism that promotes the overexpression of miR-132 in mice over its related, co-transcribed and co-regulated miRNA, miR-212. We have shown that the loop structure of miR-132 is a key determinant for its efficient processing in cells. We have also identified a range of RNA binding proteins that recognize the loop of miR-132 and influence both miR-132 and miR-212 processing. The DEAD box helicase p72/DDX17 was identified as a factor that facilitates the specific processing of miR-132. PMID:26947125

Structural landscape of the proline-rich domain of Sos1 nucleotide exchange factor.

PubMed

McDonald, Caleb B; Bhat, Vikas; Kurouski, Dmitry; Mikles, David C; Deegan, Brian J; Seldeen, Kenneth L; Lednev, Igor K; Farooq, Amjad

2013-01-01

Despite its key role in mediating a plethora of cellular signaling cascades pertinent to health and disease, little is known about the structural landscape of the proline-rich (PR) domain of Sos1 guanine nucleotide exchange factor. Herein, using a battery of biophysical tools, we provide evidence that the PR domain of Sos1 is structurally disordered and adopts an extended random coil-like conformation in solution. Of particular interest is the observation that while chemical denaturation of PR domain results in the formation of a significant amount of polyproline II (PPII) helices, it has little or negligible effect on its overall size as measured by its hydrodynamic radius. Our data also show that the PR domain displays a highly dynamic conformational basin in agreement with the knowledge that the intrinsically unstructured proteins rapidly interconvert between an ensemble of conformations. Collectively, our study provides new insights into the conformational equilibrium of a key signaling molecule with important consequences on its physiological function. Copyright © 2013 Elsevier B.V. All rights reserved.

Preparation of novel layer-stack hexagonal CdO micro-rods by a pre-oxidation and subsequent evaporation process

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

Peng, Kun, E-mail: kpeng@hnu.edu.cn; Hunan Province Key Laboratory for Spray Deposition Technology and Application, Hunan University, Changsha 410082; Jiang, Pan

2014-12-15

Graphical abstract: Layer-stack hexagonal cadmium oxide (CdO) micro-rods were prepared. - Highlights: • Novel hexagonal layer-stack structure CdO micro-rods were synthesized by a thermal evaporation method. • The pre-oxidation, vapor pressure and substrate nature play a key role on the formation of CdO rods. • The formation mechanism of CdO micro-rods was explained. - Abstract: Novel layer-stack hexagonal cadmium oxide (CdO) micro-rods were prepared by pre-oxidizing Cd granules and subsequent thermal oxidation under normal atmospheric pressure. X-ray diffraction (XRD) and scanning electron microscopy (SEM) were performed to characterize the phase structure and microstructure. The pre-oxidation process, vapor pressure and substratemore » nature were the key factors for the formation of CdO micro-rods. The diameter of micro-rod and surface rough increased with increasing of thermal evaporation temperature, the length of micro-rod increased with the increasing of evaporation time. The formation of hexagonal layer-stack structure was explained by a vapor–solid mechanism.« less

AlloRep: A Repository of Sequence, Structural and Mutagenesis Data for the LacI/GalR Transcription Regulators.

PubMed

Sousa, Filipa L; Parente, Daniel J; Shis, David L; Hessman, Jacob A; Chazelle, Allen; Bennett, Matthew R; Teichmann, Sarah A; Swint-Kruse, Liskin

2016-02-22

Protein families evolve functional variation by accumulating point mutations at functionally important amino acid positions. Homologs in the LacI/GalR family of transcription regulators have evolved to bind diverse DNA sequences and allosteric regulatory molecules. In addition to playing key roles in bacterial metabolism, these proteins have been widely used as a model family for benchmarking structural and functional prediction algorithms. We have collected manually curated sequence alignments for >3000 sequences, in vivo phenotypic and biochemical data for >5750 LacI/GalR mutational variants, and noncovalent residue contact networks for 65 LacI/GalR homolog structures. Using this rich data resource, we compared the noncovalent residue contact networks of the LacI/GalR subfamilies to design and experimentally validate an allosteric mutant of a synthetic LacI/GalR repressor for use in biotechnology. The AlloRep database (freely available at www.AlloRep.org) is a key resource for future evolutionary studies of LacI/GalR homologs and for benchmarking computational predictions of functional change. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modelling the potential role of forest thinning in maintaining water supplies under a changing climate across the conterminous United States

Treesearch

Ge Sun; Peter V. Caldwell; Steven G. McNulty

2015-01-01

The goal of this study was to test the sensitivity of water yield to forest thinning and other forest management/disturbances and climate across the conterminous United States (CONUS). Leaf area index (LAI) was selected as a key parameter linking changes in forest ecosystem structure and functions. We used the Water Supply Stress Index model to examine water yield...

Organic Crystal Engineering of Thermosetting Cyanate Ester Monomers: Influence of Structure on Melting Point

DTIC Science & Technology

2016-05-27

often discussed in the field of thermosetting materials, crystal engineering1-4 plays a key role in facilitating the successful utilization of these...not to alter the desirable properties of the polymerized networks. Fortunately, the field of crystal engineering provides examples where even very...Chickos and Acree.26 For molecular modeling, methods ranging from atomistic simulations with semi-empirical force fields to density functional

Rural Development: Information and Technical Assistance Delivered by the Department of Agriculture in Fiscal Year 1974. Fifth Annual Report to the Congress.

ERIC Educational Resources Information Center

Department of Agriculture, Washington, DC.

The key role of the U. S. Department of Agriculture (USDA) is to help local people make rural America a better place to live and work. The Rural Development (RD) Committee structure, conceived in 1969, consists of national, state, regional, and local committees which aid the USDA. During fiscal year 1974, USDA and the State Extension Services…

Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment.

PubMed

Huang, Guoyou; Li, Fei; Zhao, Xin; Ma, Yufei; Li, Yuhui; Lin, Min; Jin, Guorui; Lu, Tian Jian; Genin, Guy M; Xu, Feng

2017-10-25

The cell microenvironment has emerged as a key determinant of cell behavior and function in development, physiology, and pathophysiology. The extracellular matrix (ECM) within the cell microenvironment serves not only as a structural foundation for cells but also as a source of three-dimensional (3D) biochemical and biophysical cues that trigger and regulate cell behaviors. Increasing evidence suggests that the 3D character of the microenvironment is required for development of many critical cell responses observed in vivo, fueling a surge in the development of functional and biomimetic materials for engineering the 3D cell microenvironment. Progress in the design of such materials has improved control of cell behaviors in 3D and advanced the fields of tissue regeneration, in vitro tissue models, large-scale cell differentiation, immunotherapy, and gene therapy. However, the field is still in its infancy, and discoveries about the nature of cell-microenvironment interactions continue to overturn much early progress in the field. Key challenges continue to be dissecting the roles of chemistry, structure, mechanics, and electrophysiology in the cell microenvironment, and understanding and harnessing the roles of periodicity and drift in these factors. This review encapsulates where recent advances appear to leave the ever-shifting state of the art, and it highlights areas in which substantial potential and uncertainty remain.

Anisotropic Lithospheric Structure of Southern Madagascar from Ambient Seismic Noise

NASA Astrophysics Data System (ADS)

Dreiling, J.; Tilmann, F. J.; Yuan, X.; Rumpker, G.

2016-12-01

The island of Madagascar occupied a key region in both the assembly and the multi-stage breakup of Gondwana. Madagascar consists of amalgamated continental material comprising several distinct tectonic units. Because of its key role in the assembly of Gondwana, numerous geological and geophysical investigations have been carried out in Madagascar to understand the evolution of Gondwana.The aim of this study is to characterize the lithospheric structure of Southern Madagascar using ambient seismic noise correlation. Radial anisotropy is determined to learn about the crust/mantle deformation around the central Southern Madagascan shear zones (i.e. the Ampanihy, Beraketa and Ranotsara shear zones) and to shed light on the geological development of Madagascar and its role during the breakup of Gondwana. In the analysis we included seismic data from the SELASOMA project in Southern Madagascar, which is a passive seismic experiment carried out by the GFZ German Research Centre for Geosciences from May 2012 to May 2014. Seismic data recorded by 61 three-component seismometers were pre-processed and cross-correlated. Group velocity dispersion curves were picked manually for the vertical-vertical and transverse-transverse component correlations, which represent the Rayleigh (ZZ) and Love (TT) surface waves, respectively. Velocities from periods between 0.7 and 20 seconds are used for tomography and computation of radial anisotropy of the lithosphere.

The Role of Family in a Dietary Risk Reduction Intervention for Cardiovascular Disease.

PubMed

Schumacher, Tracy L; Burrows, Tracy L; Thompson, Deborah I; Callister, Robin; Spratt, Neil J; Collins, Clare E

2016-09-30

Diet is an essential strategy for the prevention of primary and secondary cardiovascular disease (CVD) events. The objectives were to examine: how families at increased risk of CVD perceived personal risk, their motivations to make dietary changes, their understanding of diet, and the influence of other family members. Individuals (>18 years) who completed an Australian family-based CVD risk reduction program were invited to a semi-structured telephone interview. Responses were recorded, transcribed verbatim and analysed using a systematic deductive approach with coding derived from key concepts developed as part of the interview structure. Seventeen participants from eight families were interviewed (aged 18-70 years, 47% male, five with CVD diagnosis). Key themes indicated both intrinsic and extrinsic motivations to improve heart health, variations in risk perception, recognition of the role diet plays in heart health, and the extent of family influences on eating patterns. Discrepancies between perceived and actual CVD risk perception impacted on perceived "need" to modify current dietary patterns towards heart health recommendations. Therefore, strategies not reliant on risk perception are needed to engage those with low risk perception. This could involve identifying and accessing the family "ringleader" to influence involvement and capitalising on personal accountability to other family members.

On the key role of droughts in the dynamics of summer fires in Mediterranean Europe.

PubMed

Turco, Marco; von Hardenberg, Jost; AghaKouchak, Amir; Llasat, Maria Carmen; Provenzale, Antonello; Trigo, Ricardo M

2017-03-06

Summer fires frequently rage across Mediterranean Europe, often intensified by high temperatures and droughts. According to the state-of-the-art regional fire risk projections, in forthcoming decades climate effects are expected to become stronger and possibly overcome fire prevention efforts. However, significant uncertainties exist and the direct effect of climate change in regulating fuel moisture (e.g. warmer conditions increasing fuel dryness) could be counterbalanced by the indirect effects on fuel structure (e.g. warmer conditions limiting fuel amount), affecting the transition between climate-driven and fuel-limited fire regimes as temperatures increase. Here we analyse and model the impact of coincident drought and antecedent wet conditions (proxy for the climatic factor influencing total fuel and fine fuel structure) on the summer Burned Area (BA) across all eco-regions in Mediterranean Europe. This approach allows BA to be linked to the key drivers of fire in the region. We show a statistically significant relationship between fire and same-summer droughts in most regions, while antecedent climate conditions play a relatively minor role, except in few specific eco-regions. The presented models for individual eco-regions provide insights on the impacts of climate variability on BA, and appear to be promising for developing a seasonal forecast system supporting fire management strategies.

Anion dependent self-assembly of 56-metal Cd-Ln nanoclusters with enhanced near-infrared luminescence properties

NASA Astrophysics Data System (ADS)

Yang, Xiaoping; Schipper, Desmond; Zhang, Lijie; Yang, Keqin; Huang, Shaoming; Jiang, Jijun; Su, Chengyong; Jones, Richard A.

2014-08-01

Two series of Cd-Ln clusters: nano-drum [Ln8Cd24L12(OAc)48] and nano-double-drum [Ln12Cd44L20Cl30(OAc)54] (Ln = Nd and Yb) were prepared using a flexible Schiff base ligand bearing two aryl-Br groups. Chloride (Cl-) ions, together with the interactions of Br with other electronegative atoms, play a key role in the formation of the nano-double-drums. The structures were studied by TEM and photophysical properties were determined.Two series of Cd-Ln clusters: nano-drum [Ln8Cd24L12(OAc)48] and nano-double-drum [Ln12Cd44L20Cl30(OAc)54] (Ln = Nd and Yb) were prepared using a flexible Schiff base ligand bearing two aryl-Br groups. Chloride (Cl-) ions, together with the interactions of Br with other electronegative atoms, play a key role in the formation of the nano-double-drums. The structures were studied by TEM and photophysical properties were determined. Electronic supplementary information (ESI) available: Full experimental and characterization details for 1-4. CCDC 972369-972372. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4nr03075c

Switching Cyclic Nucleotide-Selective Activation of Cyclic Adenosine Monophosphate-Dependent Protein Kinase Holoenzyme Reveals Distinct Roles of Tandem Cyclic Nucleotide-Binding Domains.

PubMed

He, Daniel; Lorenz, Robin; Kim, Choel; Herberg, Friedrich W; Lim, Chinten James

2017-12-15

The cyclic adenosine monophosphate (cAMP)- and cyclic guanosine monophosphate (cGMP)-dependent protein kinases (PKA and PKG) are key effectors of cyclic nucleotide signaling. Both share structural features that include tandem cyclic nucleotide-binding (CNB) domains, CNB-A and CNB-B, yet their functions are separated through preferential activation by either cAMP or cGMP. Based on structural studies and modeling, key CNB contact residues have been identified for both kinases. In this study, we explored the requirements for conversion of PKA activation from cAMP-dependent to cGMP-dependent. The consequences of the residue substitutions T192R/A212T within CNB-A or G316R/A336T within CNB-B of PKA-RIα on cyclic nucleotide binding and holoenzyme activation were assessed in vitro using purified recombinant proteins, and ex vivo using RIα-deficient mouse embryonic fibroblasts genetically reconstituted with wild-type or mutant PKA-RIα. In vitro, a loss of binding and activation selectivity was observed when residues in either one of the CNB domains were mutated, while mutations in both CNB domains resulted in a complete switch of selectivity from cAMP to cGMP. The switch in selectivity was also recapitulated ex vivo, confirming their functional roles in cells. Our results highlight the importance of key cyclic nucleotide contacts within each CNB domain and suggest that these domains may have evolved from an ancestral gene product to yield two distinct cyclic nucleotide-dependent protein kinases.

Intestinal microbiota composition is altered according to nutritional biorhythms in the leopard coral grouper (Plectropomus leopardus).

PubMed

Mekuchi, Miyuki; Asakura, Taiga; Sakata, Kenji; Yamaguchi, Tomofumi; Teruya, Kazuhisa; Kikuchi, Jun

2018-01-01

Aquaculture is currently a major source of fish and has the potential to become a major source of protein in the future. These demands require efficient aquaculture. The intestinal microbiota plays an integral role that benefits the host, providing nutrition and modulating the immune system. Although our understanding of microbiota in fish gut has increased, comprehensive studies examining fish microbiota and host metabolism remain limited. Here, we investigated the microbiota and host metabolism in the coral leopard grouper, which is traded in Asian markets as a superior fish and has begun to be produced via aquaculture. We initially examined the structural changes of the gut microbiota using next-generation sequencing and found that the composition of microbiota changed between fasting and feeding conditions. The dominant phyla were Proteobacteria in fasting and Firmicutes in feeding; interchanging the dominant bacteria required 12 hours. Moreover, microbiota diversity was higher under feeding conditions than under fasting conditions. Multivariate analysis revealed that Proteobacteria are the key bacteria in fasting and Firmicutes and Fusobacteria are the key bacteria in feeding. Subsequently, we estimated microbiota functional capacity. Microbiota functional structure was relatively stable throughout the experiment; however, individual function activity changed according to feeding conditions. Taken together, these findings indicate that the gut microbiota could be a key factor to understanding fish feeding conditions and play a role in interactions with host metabolism. In addition, the composition of microbiota in ambient seawater directly affects the fish; therefore, it is important to monitor the microbiota in rearing tanks and seawater circulating systems.

Insulin-like growth factor (IGF) signalling is required for early dorso-anterior development of the zebrafish embryo.

PubMed

Eivers, Edward; McCarthy, Karena; Glynn, Catherine; Nolan, Catherine M; Byrnes, Lucy

2004-12-01

The insulin-like growth factor (IGF) signalling pathway has been highly conserved in animal evolution and, in mammals and Xenopus, plays a key role in embryonic growth and development, with the IGF-1 receptor (IGF-1R) being a crucial regulator of the signalling cascade. Here we report the first functional role for the IGF pathway in zebrafish. Expression of mRNA coding for a dominant negative IGF-1R resulted in embryos that were small in size compared to controls and had disrupted head and CNS development. At its most extreme, this phenotype was characterized by a complete loss of head and eye structures, an absence of notochord and the presence of abnormal somites. In contrast, up-regulation of IGF signalling following injection of IGF-1 mRNA, resulted in a greatly expanded development of anterior structures at the expense of trunk and tail. IGF-1R knockdown caused a significant decrease in the expression of Otx2, Rx3, FGF8, Pax6.2 and Ntl, while excess IGF signalling expanded Otx2 expression in presumptive forebrain tissue and widened the Ntl expression domain in the developing notochord. The observation that IGF-1R knockdown reduced expression of two key organizer genes (chordin and goosecoid) suggests that IGF signalling plays a role in regulating zebrafish organizer activity. This is supported by the expression of IGF-1, IGF-2 and IGF-1R in shield-stage zebrafish embryos and the demonstration that IGF signalling influences expression of BMP2b, a gene that plays an important role in zebrafish pattern formation. Our data is consistent with a common pathway for integration of IGF, FGF8 and anti-BMPs in early vertebrate development.

Evolution of egg coats: linking molecular biology and ecology.

PubMed

Shu, Longfei; Suter, Marc J-F; Räsänen, Katja

2015-08-01

One central goal of evolutionary biology is to explain how biological diversity emerges and is maintained in nature. Given the complexity of the phenotype and the multifaceted nature of inheritance, modern evolutionary ecological studies rely heavily on the use of molecular tools. Here, we show how molecular tools help to gain insight into the role of egg coats (i.e. the extracellular structures surrounding eggs and embryos) in evolutionary diversification. Egg coats are maternally derived structures that have many biological functions from mediating fertilization to protecting the embryo from environmental hazards. They show great molecular, structural and functional diversity across species, but intraspecific variability and the role of ecology in egg coat evolution have largely been overlooked. Given that much of the variation that influences egg coat function is ultimately determined by their molecular phenotype, cutting-edge molecular tools (e.g. proteomics, glycomics and transcriptomics), combined with functional assays, are needed for rigorous inferences on their evolutionary ecology. Here, we identify key research areas and highlight emerging molecular techniques that can increase our understanding of the role of egg coats in the evolution of biological diversity, from adaptation to speciation. © 2015 John Wiley & Sons Ltd.

Transforming the Delivery of Care in the Post–Health Reform Era: What Role Will Community Health Workers Play?

PubMed Central

Ro, Marguerite; Villa, Normandy William; Powell, Wayne; Knickman, James R.

2011-01-01

The Patient Protection and Affordable Care Act (PPACA) affords opportunities to sustain the role of community health workers (CHWs). Among myriad strategies encouraged by PPACA are prevention and care coordination, particularly for chronic diseases, chief drivers of increased health care costs. Prevention and care coordination are functions that have been performed by CHWs for decades, particularly among underserved populations. The two key delivery models promoted in the PPACA are accountable care organizations and health homes. Both stress the importance of interdisciplinary, interprofessional health care teams, the ideal context for integrating CHWs. Equally important, the payment structures encouraged by PPACA to support these delivery models offer the vehicles to sustain the role of these valued workers. PMID:22021289

The serotonergic system and anxiety.

PubMed

Gordon, Joshua A; Hen, Rene

2004-01-01

The wide use of serotonin reuptake inhibitors and serotonin receptor agonists in anxiety disorders has suggested a key role for the modulatory neurotransmitter in anxiety. However, serotonin's specific role is still uncertain. This article reviews the literature concerning how and where serotonergic agents modulate anxiety. Varying and sometimes conflicting data from human and animal studies argue for both anxiolytic and anxiogenic roles for serotonin, depending on the specific disorder, structure, or behavioral task studied. However, recent data from molecular genetic studies in the mouse point toward two important roles for the serotonin 1A receptor. In development, serotonin acts through this receptor to promote development of the circuitry necessary for normal anxiety-like behaviors. In adulthood, serotonin reuptake inhibitors act through the same receptor to stimulate neurogenesis and reduce anxiety-like behaviors. These studies highlight that the complex serotonin system likely plays various roles in the regulation of anxiety both during development and in adulthood.

Central nervous system-specific knockout of steroidogenic factor 1 results in increased anxiety-like behavior.

PubMed

Zhao, Liping; Kim, Ki Woo; Ikeda, Yayoi; Anderson, Kimberly K; Beck, Laurel; Chase, Stephanie; Tobet, Stuart A; Parker, Keith L

2008-06-01

Steroidogenic factor 1 (SF-1) plays key roles in adrenal and gonadal development, expression of pituitary gonadotropins, and development of the ventromedial hypothalamic nucleus (VMH). If kept alive by adrenal transplants, global knockout (KO) mice lacking SF-1 exhibit delayed-onset obesity and decreased locomotor activity. To define specific roles of SF-1 in the VMH, we used the Cre-loxP system to inactivate SF-1 in a central nervous system (CNS)-specific manner. These mice largely recapitulated the VMH structural defect seen in mice lacking SF-1 in all tissues. In multiple behavioral tests, mice with CNS-specific KO of SF-1 had significantly more anxiety-like behavior than wild-type littermates. The CNS-specific SF-1 KO mice had diminished expression or altered distribution in the mediobasal hypothalamus of several genes whose expression has been linked to stress and anxiety-like behavior, including brain-derived neurotrophic factor, the type 2 receptor for CRH (Crhr2), and Ucn 3. Moreover, transfection and EMSAs support a direct role of SF-1 in Crhr2 regulation. These findings reveal important roles of SF-1 in the hypothalamic expression of key regulators of anxiety-like behavior, providing a plausible molecular basis for the behavioral effect of CNS-specific KO of this nuclear receptor.

Plant community, geographic distance and abiotic factors play different roles in predicting AMF biogeography at the regional scale in northern China.

PubMed

Xu, Tianle; Veresoglou, Stavros D; Chen, Yongliang; Rillig, Matthias C; Xiang, Dan; Ondřej, Daniel; Hao, Zhipeng; Liu, Lei; Deng, Ye; Hu, Yajun; Chen, Weiping; Wang, Juntao; He, Jizheng; Chen, Baodong

2016-12-01

Arbuscular mycorrhizal fungi (AMF) are ubiquitous mutualists of terrestrial plants and play key roles in regulating various ecosystem processes, but little is known about AMF biogeography at regional scale. This study aims at exploring the key predictors of AMF communities across a 5000-km transect in northern China. We determined the soil AMF species richness and community composition at 47 sites representative of four vegetation types (meadow steppe, typical steppe, desert steppe and desert) and related them to plant community characteristics, abiotic factors and geographic distance. The results showed that soil pH was the strongest predictor of AMF richness and phylogenetic diversity. However, abiotic factors only have a low predictive effect on AMF community composition or phylogenetic patterns. By contrast, we found a significant relationship between community composition of AMF and plants, which was a surprising result given the extent of heterogeneity in the plant community across this transect. Moreover, the geographic distance predominantly explained the AMF phylogenetic structure, implying that history evolutionary may play a role in shaping AMF biogeographic patterns. This study highlighted the different roles of main factors in predicting AMF biogeography, and bridge landscape-scale studies to more recent global-scale efforts. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

The Role of Protein Loops and Linkers in Conformational Dynamics and Allostery.

PubMed

Papaleo, Elena; Saladino, Giorgio; Lambrughi, Matteo; Lindorff-Larsen, Kresten; Gervasio, Francesco Luigi; Nussinov, Ruth

2016-06-08

Proteins are dynamic entities that undergo a plethora of conformational changes that may take place on a wide range of time scales. These changes can be as small as the rotation of one or a few side-chain dihedral angles or involve concerted motions in larger portions of the three-dimensional structure; both kinds of motions can be important for biological function and allostery. It is becoming increasingly evident that "connector regions" are important components of the dynamic personality of protein structures. These regions may be either disordered loops, i.e., poorly structured regions connecting secondary structural elements, or linkers that connect entire protein domains. Experimental and computational studies have, however, revealed that these regions are not mere connectors, and their role in allostery and conformational changes has been emerging in the last few decades. Here we provide a detailed overview of the structural properties and classification of loops and linkers, as well as a discussion of the main computational methods employed to investigate their function and dynamical properties. We also describe their importance for protein dynamics and allostery using as examples key proteins in cellular biology and human diseases such as kinases, ubiquitinating enzymes, and transcription factors.

Spectroscopic Studies of the Chan-Lam Amination: A Mechanism-Inspired Solution to Boronic Ester Reactivity.

PubMed

Vantourout, Julien C; Miras, Haralampos N; Isidro-Llobet, Albert; Sproules, Stephen; Watson, Allan J B

2017-04-05

We report an investigation of the Chan-Lam amination reaction. A combination of spectroscopy, computational modeling, and crystallography has identified the structures of key intermediates and allowed a complete mechanistic description to be presented, including off-cycle inhibitory processes, the source of amine and organoboron reactivity issues, and the origin of competing oxidation/protodeboronation side reactions. Identification of key mechanistic events has allowed the development of a simple solution to these issues: manipulating Cu(I) → Cu(II) oxidation and exploiting three synergistic roles of boric acid has allowed the development of a general catalytic Chan-Lam amination, overcoming long-standing and unsolved amine and organoboron limitations of this valuable transformation.

Oncology Nurse Navigation: Results of the 2016 Role Delineation Study.

PubMed

Lubejko, Barbara G; Bellfield, Sonia; Kahn, Elisa; Lee, Carrie; Peterson, Nicole; Rose, Traudi; Murphy, Cynthia Miller; McCorkle, Michele

2017-02-01

In 2011, an oncology nurse navigator (ONN) role delineation survey (RDS) was conducted by the Oncology Nursing Society (ONS) when the role was relatively new to oncology. Results did not demonstrate a unique skill set for the ONN; however, since then, the role has expanded. ONS and the Oncology Nursing Certification Corporation partnered in 2016 to complete an RDS of ONNs to redefine the role and determine the need for an ONN certification examination. A structured RDS was conducted using a formal consensus-building process. A survey was developed and released to examine the specific tasks, knowledge, and skills for the ONN as well as to determine which role possesses more responsibility for the tasks. The ONN role is evolving, and more was learned about its key tasks, including differences in the responsibilities of the ONN and the clinical or staff nurse. However, the RDS did not find an adequate difference in the knowledge required by the ONN and the clinical or staff nurse to support the need for a separate ONN certification.

High-resolution structure of the Escherichia coli ribosome

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

Noeske, Jonas; Wasserman, Michael R.; Terry, Daniel S.

Protein synthesis by the ribosome is highly dependent on the ionic conditions in the cellular environment, but the roles of ribosome solvation remain poorly understood. Moreover, the function of modifications to ribosomal RNA and ribosomal proteins are unclear. Here we present the structure of the Escherichia coli 70S ribosome to 2.4 Å resolution. The structure reveals details of the ribosomal subunit interface that are conserved in all domains of life, and suggest how solvation contributes to ribosome integrity and function. The structure also suggests how the conformation of ribosomal protein uS12 likely impacts its contribution to messenger RNA decoding. Inmore » conclusion, this structure helps to explain the phylogenetic conservation of key elements of the ribosome, including posttranscriptional and posttranslational modifications and should serve as a basis for future antibiotic development.« less

High-resolution structure of the Escherichia coli ribosome

DOE PAGES

Noeske, Jonas; Wasserman, Michael R.; Terry, Daniel S.; ...

2015-03-16

Protein synthesis by the ribosome is highly dependent on the ionic conditions in the cellular environment, but the roles of ribosome solvation remain poorly understood. Moreover, the function of modifications to ribosomal RNA and ribosomal proteins are unclear. Here we present the structure of the Escherichia coli 70S ribosome to 2.4 Å resolution. The structure reveals details of the ribosomal subunit interface that are conserved in all domains of life, and suggest how solvation contributes to ribosome integrity and function. The structure also suggests how the conformation of ribosomal protein uS12 likely impacts its contribution to messenger RNA decoding. Inmore » conclusion, this structure helps to explain the phylogenetic conservation of key elements of the ribosome, including posttranscriptional and posttranslational modifications and should serve as a basis for future antibiotic development.« less

Contingency management: perspectives of Australian service providers.

PubMed

Cameron, Jacqui; Ritter, Alison

2007-03-01

Given the very positive and extensive research evidence demonstrating efficacy and effectiveness of contingency management, it is important that Australia explore whether contingency management has a role to play in our own treatment context. Qualitative interviews were conducted with 30 experienced alcohol and drug practitioners, service managers and policy-makers in Victoria. Interviewees were selected to represent the range of drug treatment services types and included rural representation. A semi-structured interview schedule, covering their perceptions and practices of contingency management was used. All interviews were transcribed verbatim and analysed using N2 qualitative data analysis program. The majority of key informants were positively inclined toward contingency management, notwithstanding some concerns about the philosophical underpinnings. Concerns were raised in relation to the use of monetary rewards. Examples of the use of contingency management provided by key informants demonstrated an over-inclusive definition: all the examples did not adhere to the key principles of contingency management. This may create problems if a structured contingency management were to be introduced in Australia. Contingency management is an important adjunctive treatment intervention and its use in Australia has the potential to enhance treatment outcomes. No unmanageable barriers were identified in this study.

Structural Rheology of the Smectic Phase

PubMed Central

Fujii, Shuji; Komura, Shigeyuki; Lu, Chun-Yi David

2014-01-01

In this review article, we discuss the rheological properties of the thermotropic smectic liquid crystal 8CB with focal conic domains (FCDs) from the viewpoint of structural rheology. It is known that the unbinding of the dislocation loops in the smectic phase drives the smectic-nematic transition. Here we discuss how the unbinding of the dislocation loops affects the evolution of the FCD size, linear and nonlinear rheological behaviors of the smectic phase. By studying the FCD formation from the perpendicularly oriented smectic layers, we also argue that dislocations play a key role in the structural development in layered systems. Furthermore, similarities in the rheological behavior between the FCDs in the smectic phase and the onion structures in the lyotropic lamellar phase suggest that these systems share a common physical origin for the elasticity. PMID:28788123

Hydrodynamic fabrication of structurally gradient ZnO nanorods.

PubMed

Kim, Hyung Min; Youn, Jae Ryoun; Song, Young Seok

2016-02-26

We studied a new approach where structurally gradient nanostructures were fabricated by means of hydrodynamics. Zinc oxide (ZnO) nanorods were synthesized in a drag-driven rotational flow in a controlled manner. The structural characteristics of nanorods such as orientation and diameter were determined by momentum and mass transfer at the substrate surface. The nucleation of ZnO was induced by shear stress which plays a key role in determining the orientation of ZnO nanorods. The nucleation and growth of such nanostructures were modeled theoretically and analyzed numerically to understand the underlying physics of the fabrication of nanostructures controlled by hydrodynamics. The findings demonstrated that the precise control of momentum and mass transfer enabled the formation of ZnO nanorods with a structural gradient in diameter and orientation.

Ultrasonic Signal Processing for Structural Health Monitoring

NASA Astrophysics Data System (ADS)

Michaels, Jennifer E.; Michaels, Thomas E.

2004-02-01

Permanently mounted ultrasonic sensors are a key component of systems under development for structural health monitoring. Signal processing plays a critical role in the viability of such systems due to the difficulty in interpreting signals received from structures of complex geometry. This paper describes a differential feature-based approach to classifying signal changes as either "environmental" or "structural". Data are presented from piezoelectric discs bonded to an aluminum specimen subjected to both environmental changes and introduction of artificial defects. The classifier developed as part of this study was able to correctly identify artificial defects that were not part of the initial training and evaluation data sets. Central to the success of the classifier was the use of the Short Time Cross Correlation to measure coherency between the signal and reference as a function of time.

The Yeast Nuclear Pore Complex and Transport Through It

PubMed Central

Aitchison, John D.; Rout, Michael P.

2012-01-01

Exchange of macromolecules between the nucleus and cytoplasm is a key regulatory event in the expression of a cell’s genome. This exchange requires a dedicated transport system: (1) nuclear pore complexes (NPCs), embedded in the nuclear envelope and composed of proteins termed nucleoporins (or “Nups”), and (2) nuclear transport factors that recognize the cargoes to be transported and ferry them across the NPCs. This transport is regulated at multiple levels, and the NPC itself also plays a key regulatory role in gene expression by influencing nuclear architecture and acting as a point of control for various nuclear processes. Here we summarize how the yeast Saccharomyces has been used extensively as a model system to understand the fundamental and highly conserved features of this transport system, revealing the structure and function of the NPC; the NPC’s role in the regulation of gene expression; and the interactions of transport factors with their cargoes, regulatory factors, and specific nucleoporins. PMID:22419078

Supporting Parents' Pain Care Involvement With Their Children With Acute Lymphoblastic Leukemia: A Qualitative Interpretive Description.

PubMed

Bettle, Amanda; Latimer, Margot; Fernandez, Conrad; Hughes, Jean

Children with acute lymphoblastic leukemia experience pain from the disease, treatment, and procedures. Parents can be effective in managing their child's pain, but little is systematically known about how they do this. Appreciative inquiry was used to frame the study within a strengths-based lens and interpretive descriptive methods were used to describe pain sources, parents' pain care role, and key structures supporting parents pain care involvement. Eight paediatric oncology clinic nurses and 10 parents participated. Six key themes per group were identified. Parent themes included establishing therapeutic relationships, relearning how to care for my child, overcoming challenges and recognizing pain, learning parent specific strategies, empowering to take active pain care role, and maintaining relationships. Nurse themes included establishing therapeutic relationships, preparing parents to care for their child, facilitating pain assessment, teaching parents best pain care, empowering parents, and maintaining relationships. These findings can be used to guide clinical practice and future research.

Role of magnetic fluctuations in mode selection of magnetically driven instabilities

NASA Astrophysics Data System (ADS)

Dan, Jia-Kun; Ren, Xiao-Dong; Huang, Xian-Bin; Ouyang, Kai; Chen, Guang-Hua

2014-12-01

The influences of magnetic fluctuations on quasiperiodic structure formation and fundamental wavelength selection of the instability have been studied using two 25-μm-diameter tungsten wires on a 100 ns rise time, 220 kA pulsed power facility. Two different load configurations were adopted to make end surfaces of electrodes approximately satisfy reflecting and absorbing boundary conditions, respectively. The experimental results that the fundamental wavelength in the case of absorbing boundary condition is about one half of that in the case of reflecting boundary condition have demonstrated that magnetic fluctuations appear to play a key role in mode selection of magnetically driven instabilities. The dominant wavelength should be proportional to magnetic field and inversely proportional to square root of mass density, provided that the magnetosonic wave propagating perpendicular to magnetic fields provides a leading candidate for magnetic fluctuations. Therefore, magnetic fluctuation is one of the three key perturbations, along with surface contaminants and surface roughness, that seeds magnetically driven instabilities.

The X-ray Crystal Structure of the Phage Tail Terminator Protein Reveals the Biologically Relevant Hexameric Rang Structure and Demonstrates a Conserved mechanism of Tail Termination among Divrse Long Tailed Phages

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

Pell, L.; Liu, A; Edmonds, L

The tail terminator protein (TrP) plays an essential role in phage tail assembly by capping the rapidly polymerizing tail once it has reached its requisite length and serving as the interaction surface for phage heads. Here, we present the 2.7-A crystal structure of a hexameric ring of gpU, the TrP of phage ?. Using sequence alignment analysis and site-directed mutagenesis, we have shown that this multimeric structure is biologically relevant and we have delineated its functional surfaces. Comparison of the hexameric crystal structure with the solution structure of gpU that we previously solved using NMR spectroscopy shows large structural changesmore » occurring upon multimerization and suggests a mechanism that allows gpU to remain monomeric at high concentrations on its own, yet polymerize readily upon contact with an assembled tail tube. The gpU hexamer displays several flexible loops that play key roles in head and tail binding, implying a role for disorder-to-order transitions in controlling assembly as has been observed with other ? morphogenetic proteins. Finally, we have found that the hexameric structure of gpU is very similar to the structure of a putative TrP from a contractile phage tail even though it displays no detectable sequence similarity. This finding coupled with further bioinformatic investigations has led us to conclude that the TrPs of non-contractile-tailed phages, such as ?, are evolutionarily related to those of contractile-tailed phages, such as P2 and Mu, and that all long-tailed phages may utilize a conserved mechanism for tail termination.« less

High renewable content sandwich structures based on flax-basalt hybrids and biobased epoxy polymers

NASA Astrophysics Data System (ADS)

Colomina, S.; Boronat, T.; Fenollar, O.; Sánchez-Nacher, L.; Balart, R.

2014-05-01

In the last years, a growing interest in the development of high environmental efficiency materials has been detected and this situation is more accentuated in the field of polymers and polymer composites. In this work, green composite sandwich structures with high renewable content have been developed with core cork materials. The base resin for composites was a biobased epoxy resin derived from epoxidized vegetable oils. Hybrid basalt-flax fabrics have been used as reinforcements for composites and the influence of the stacking sequence has been evaluated in order to optimize the appropriate laminate structure for the sandwich bases. Core cork materials with different thickness have been used to evaluate performance of sandwich structures thus leading to high renewable content composite sandwich structures. Results show that position of basalt fabrics plays a key role in flexural fracture of sandwich structures due to differences in stiffness between flax and basalt fibers.

Implementing health and social care integration in Scotland: Renegotiating new partnerships in changing cultures of care.

PubMed

Pearson, Charlotte; Watson, Nick

2018-05-01

Health and social care integration has been a long-term goal for successive governments in Scotland, culminating in the implementation of the recent Public Bodies (Joint Working) Scotland Act 2014. This laid down the foundations for the delegation of health and social care functions and resources to newly formed Integrated Joint Boards. It put in place demands for new ways of working and partnership planning. In this article, we explore the early implementation of this Act and how health and social care professionals and the third sector have begun to renegotiate their roles. The paper draws on new empirical data collated through focus groups and interviews with over 70 professionals from across Scotland. The data are explored through the following key themes: changing cultures, structural imbalance, governance and partnership and the role of individuals or "boundary spanners" in implementing change. We also draw on evidence from other international systems of care, which have implemented integration policies, documenting what works and what does not. We argue that under the current framework much of the potential for integration is not being fulfilled and that the evidence suggests that at this early stage of roll-out, the structural and cultural policy changes that are required to enable this policy shift have not yet emerged. Rather, integration has been left to individual innovators or "boundary spanners" and these are acting as key drivers of change. Where change is occurring, this is happening despite the system. As it is currently structured, we argue that too much power is in the hands of health and despite the rhetoric of partnership working, there are real structural imbalances that need to be reconciled. © 2018 John Wiley & Sons Ltd.

Short-term memory for spatial, sequential and duration information.

PubMed

Manohar, Sanjay G; Pertzov, Yoni; Husain, Masud

2017-10-01

Space and time appear to play key roles in the way that information is organized in short-term memory (STM). Some argue that they are crucial contexts within which other stored features are embedded, allowing binding of information that belongs together within STM. Here we review recent behavioral, neurophysiological and imaging studies that have sought to investigate the nature of spatial, sequential and duration representations in STM, and how these might break down in disease. Findings from these studies point to an important role of the hippocampus and other medial temporal lobe structures in aspects of STM, challenging conventional accounts of involvement of these regions in only long-term memory.

Laboratory Information Systems.

PubMed

Henricks, Walter H

2015-06-01

Laboratory information systems (LISs) supply mission-critical capabilities for the vast array of information-processing needs of modern laboratories. LIS architectures include mainframe, client-server, and thin client configurations. The LIS database software manages a laboratory's data. LIS dictionaries are database tables that a laboratory uses to tailor an LIS to the unique needs of that laboratory. Anatomic pathology LIS (APLIS) functions play key roles throughout the pathology workflow, and laboratories rely on LIS management reports to monitor operations. This article describes the structure and functions of APLISs, with emphasis on their roles in laboratory operations and their relevance to pathologists. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of Electronegativity on Bipolar Resistive Switching in a WO3-Based Asymmetric Capacitor Structure.

PubMed

Kim, Jongmin; Inamdar, Akbar I; Jo, Yongcheol; Woo, Hyeonseok; Cho, Sangeun; Pawar, Sambhaji M; Kim, Hyungsang; Im, Hyunsik

2016-04-13

This study investigates the transport and switching time of nonvolatile tungsten oxide based resistive-switching (RS) memory devices. These devices consist of a highly resistive tungsten oxide film sandwiched between metal electrodes, and their RS characteristics are bipolar in the counterclockwise direction. The switching voltage, retention, endurance, and switching time are strongly dependent on the type of electrodes used, and we also find quantitative and qualitative evidence that the electronegativity (χ) of the electrodes plays a key role in determining the RS properties and switching time. We also propose an RS model based on the role of the electronegativity at the interface.

Building a functional artery: issues from the perspective of mechanics.

PubMed

Gleason, Rudolph L; Hu, Jin-Jia; Humphrey, Jay D

2004-09-01

Despite the many successes of arterial tissue engineering, clinically viable implants may be a decade or more away. Fortunately, there is much more that we can learn from native vessels with regard to designing for optimal structure, function, and properties. Herein, we examine recent observations in vascular biology from the perspective of nonlinear mechanics. Moreover, we use a constrained mixture model to study potential contributions of individual wall constituents. In both cases, the unique biological and mechanical roles of elastin come to the forefront, especially its role in generating and modulating residual stress within the wall, which appears to be key to multiple growth and remodeling responses.

How can core self-evaluations influence job burnout? The key roles of organizational commitment and job satisfaction.

PubMed

Peng, Jiaxi; Li, Dongdong; Zhang, Zhenjiang; Tian, Yu; Miao, Danmin; Xiao, Wei; Zhang, Jiaxi

2016-01-01

This study aimed to explore how core self-evaluations influenced job burnout and mainly focused on the confirmation of the mediator roles of organizational commitment and job satisfaction. A total of 583 female nurses accomplished the Core Self-Evaluation Scale, Organizational Commitment Scale, Minnesota Satisfaction Questionnaire, and Maslach Burnout Inventory-General Survey. The results revealed that core self-evaluations, organizational commitment, job satisfaction, and job burnout were significantly correlated with each other. Structural equation modeling indicated that core self-evaluations can significantly influence job burnout and are completely mediated by organizational commitment and job satisfaction. © The Author(s) 2014.

Solar heating and the electric utilities

NASA Astrophysics Data System (ADS)

Maidique, M. A.; Woo, B.

1980-05-01

The article considers the effect of widespread use of solar thermal systems on the role of electric utilities, emphasizing the foreseen short term economic problems. While the average electricity demand will be reduced, infrequent high demand peaks could occur when on nights and certain days, solar users with inadequate storage capacity are forced to depend upon conventional energy sources. Since utility costs are closely related to changes in peak demands, the modification of electricity rate structures as a load management technique is discussed. Some advantages of wide solar energy application for electric utilities are cited including the possibility of their key role in the development of solar heating.

Adjustment to loss of the driving role following traumatic brain injury: a qualitative exploration with key stakeholders.

PubMed

Liddle, Jacki; Fleming, Jennifer; McKenna, Kryss; Turpin, Merrill; Whitelaw, Penny; Allen, Shelley

2012-02-01

Community mobility is affected by an interruption to or cessation of driving following traumatic brain injury (TBI). This study aimed to examine loss of the driving role and to explore the outcomes associated with driving cessation from the perspectives of key people involved within the process: people with TBI, their family members and involved health professionals. A qualitative methodology was used, employing semi-structured interviews with 15 individuals with TBI who had experienced driving cessation, 10 family members and 10 health professionals working with this population. This article focuses on two themes, each with three subthemes. Being stuck: needs related to driving cessation had subthemes: (i) an emotional time, (ii) being normal and (iii) participation without driving. The second theme, A better way: suggestions to improve outcomes had subthemes: (i) information, (ii) support and trying it out and (iii) their family member's roles and needs. Driving cessation following TBI is associated with emotional, identity, transport and participation-related needs. An ongoing, individualised approach involving information, support and practical experiences may improve outcomes of driving cessation for people with TBI and their family members. © 2011 The Authors. Australian Occupational Therapy Journal © 2011 Occupational Therapy Australia.

Wig1 prevents cellular senescence by regulating p21 mRNA decay through control of RISC recruitment

PubMed Central

Kim, Bong Cho; Lee, Hyung Chul; Lee, Je-Jung; Choi, Chang-Min; Kim, Dong-Kwan; Lee, Jae Cheol; Ko, Young-Gyu; Lee, Jae-Seon

2012-01-01

Premature senescence, a key strategy used to suppress carcinogenesis, can be driven by p53/p21 proteins in response to various stresses. Here, we demonstrate that Wig1 plays a critical role in this process through regulation of p21 mRNA stability. Wig1 controls the association of Argonaute2 (Ago2), a central component of the RNA-induced silencing complex (RISC), with target p21 mRNA via binding of the stem-loop structure near the microRNA (miRNA) target site. Depletion of Wig1 prohibited miRNA-mediated p21 mRNA decay and resulted in premature senescence. Wig1 plays an essential role in cell proliferation, as demonstrated in tumour xenografts in mice, and Wig1 and p21 mRNA levels are inversely correlated in human normal and cancer tissues. Together, our data indicate a novel role of Wig1 in RISC target accessibility, which is a key step in RNA-mediated gene silencing. In addition, these findings indicate that fine-tuning of p21 levels by Wig1 is essential for the prevention of cellular senescence. PMID:23085987

Wig1 prevents cellular senescence by regulating p21 mRNA decay through control of RISC recruitment.

PubMed

Kim, Bong Cho; Lee, Hyung Chul; Lee, Je-Jung; Choi, Chang-Min; Kim, Dong-Kwan; Lee, Jae Cheol; Ko, Young-Gyu; Lee, Jae-Seon

2012-11-14

Premature senescence, a key strategy used to suppress carcinogenesis, can be driven by p53/p21 proteins in response to various stresses. Here, we demonstrate that Wig1 plays a critical role in this process through regulation of p21 mRNA stability. Wig1 controls the association of Argonaute2 (Ago2), a central component of the RNA-induced silencing complex (RISC), with target p21 mRNA via binding of the stem-loop structure near the microRNA (miRNA) target site. Depletion of Wig1 prohibited miRNA-mediated p21 mRNA decay and resulted in premature senescence. Wig1 plays an essential role in cell proliferation, as demonstrated in tumour xenografts in mice, and Wig1 and p21 mRNA levels are inversely correlated in human normal and cancer tissues. Together, our data indicate a novel role of Wig1 in RISC target accessibility, which is a key step in RNA-mediated gene silencing. In addition, these findings indicate that fine-tuning of p21 levels by Wig1 is essential for the prevention of cellular senescence.

The internal processes and behavioral dynamics of hospital boards: an exploration of differences between high- and low-performing hospitals.

PubMed

Kane, Nancy M; Clark, Jonathan R; Rivenson, Howard L

2009-01-01

Nonprofit hospital boards are under increasing pressure to improve financial, clinical, and charitable and community benefit performance. Most research on board effectiveness focuses on variables measuring board structure and attributes associated with competing ideal models of board roles. However, the results do not provide clear evidence that one role is superior to another and suggest that in practice boards pursue hybrid roles. Board dynamics and processes have received less attention from researchers, but emerging theoretical frameworks highlight them as key to effective corporate governance. We explored differences in board processes and behavioral dynamics between financially high- and low-performing hospitals, with the goal of developing a better understanding of the best board practices in nonprofit hospitals. A comparative case study approach allowed for in-depth, qualitative assessments of how the internal workings of boards differ between low- and high-performing facilities. Boards of hospitals with strong financial performance exhibited behavioral dynamics and internal processes that differed in important ways from those of hospitals with poor financial performance. Boards need to actively attend to key processes and foster positive group dynamics in decision making to be more effective in governing hospitals.

Roles, processes, and outcomes of interprofessional shared decision-making in a neonatal intensive care unit: A qualitative study.

PubMed

Dunn, Sandra I; Cragg, Betty; Graham, Ian D; Medves, Jennifer; Gaboury, Isabelle

2018-05-01

Shared decision-making provides an opportunity for the knowledge and skills of care providers to synergistically influence patient care. Little is known about interprofessional shared decision-making processes in critical care settings. The aim of this study was to explore interprofessional team members' perspectives about the nature of interprofessional shared decision-making in a neonatal intensive care unit (NICU) and to determine if there are any differences in perspectives across professional groups. An exploratory qualitative approach was used consisting of semi-structured interviews with 22 members of an interprofessional team working in a tertiary care NICU in Canada. Participants identified four key roles involved in interprofessional shared decision-making: leader, clinical experts, parents, and synthesizer. Participants perceived that interprofessional shared decision-making happens through collaboration, sharing, and weighing the options, the evidence and the credibility of opinions put forward. The process of interprofessional shared decision-making leads to a well-informed decision and participants feeling valued. Findings from this study identified key concepts of interprofessional shared decision-making, increased awareness of differing professional perspectives about this process of shared decision-making, and clarified understanding of the different roles involved in the decision-making process in an NICU.

Brain abnormalities in antisocial individuals: implications for the law.

PubMed

Yang, Yaling; Glenn, Andrea L; Raine, Adrian

2008-01-01

With the increasing popularity in the use of brain imaging on antisocial individuals, an increasing number of brain imaging studies have revealed structural and functional impairments in antisocial, psychopathic, and violent individuals. This review summarizes key findings from brain imaging studies on antisocial/aggressive behavior. Key regions commonly found to be impaired in antisocial populations include the prefrontal cortex (particularly orbitofrontal and dorsolateral prefrontal cortex), superior temporal gyrus, amygdala-hippocampal complex, and anterior cingulate cortex. Key functions of these regions are reviewed to provide a better understanding on how deficits in these regions may predispose to antisocial behavior. Objections to the use of imaging findings in a legal context are outlined, and alternative perspectives raised. It is argued that brain dysfunction is a risk factor for antisocial behavior and that it is likely that imaging will play an increasing (albeit limited) role in legal decision-making. (c) 2008 John Wiley & Sons, Ltd.

Key Factors for a High-Quality Peritoneal Dialysis Program — The Role of the PD Team and Continuous Quality Improvement

PubMed Central

Fang, Wei; Ni, Zhaohui; Qian, Jiaqi

2014-01-01

The proportion of end-stage renal disease (ESRD) patients on peritoneal dialysis (PD) has increased very fast in China over the last decade. Renji Hospital, affiliated with Shanghai Jiaotong University School of Medicine, is a recognized high-quality PD unit with a high PD utilization rate, excellent patient and technique survival (1-year and 5-year patient survival rate of 93% and 71%, and 1-year and 5-year technique survival of 96% and 82%, respectively), low peritonitis rate and a well-documented good quality of life of the treated patients. We believe that a dedicated and experienced PD team, a structured patient training program, continuous patient support, establishing and utilizing standardized protocols, starting PD with low dialysis dose, monitoring key performance indicators (KPIs), and continuous quality improvement (CQI) are the key factors underlying this successful PD program. PMID:24962961

Innovative Seismological Techniques for Investigating the Interior Structure of Venus

NASA Astrophysics Data System (ADS)

Stevenson, D. J.; Cutts, J. A.; Mimoun, D.

2014-12-01

The formation, evolution and structure of Venus remain a mystery more than fifty years after the first visit by a robotic spacecraft. Radar images have revealed a surface that is much younger than those of the Moon, Mercury and Mars as well as a variety of enigmatic volcanic and tectonic features quite unlike those generated by plate tectonics on Earth. To understand how Venus works as a planet it is necessary to probe the interior of Venus. To accomplish this seismology must play a key role. Conventional seismology employs sensors in contact with the planetary surface but for Venus theses sensors must tolerate the Venus environment (460oC and 90 bars) for up to a year. The dense atmosphere of Venus, which efficiently couples seismic energy into the atmosphere as infrasonic waves, enables an alternative: detection of infrasonic waves in the upper atmosphere using either high altitude balloons or orbiting spacecraft. In June 2014, the Keck Institute for Space Studies (KISS) at the California Institute of Technology sponsored a one week workshop with 30 specialists in the key techniques and technologies that can bring these technique to readiness. In this paper, we describe the key synergies with earth science drawing on methods from terrestrial seismology and oceanography and identify key technical issues that need to be solved as well as important precursor measurements that should be made.

NASA Integrated Model Centric Architecture (NIMA) Model Use and Re-Use

NASA Technical Reports Server (NTRS)

Conroy, Mike; Mazzone, Rebecca; Lin, Wei

2012-01-01

This whitepaper accepts the goals, needs and objectives of NASA's Integrated Model-centric Architecture (NIMA); adds experience and expertise from the Constellation program as well as NASA's architecture development efforts; and provides suggested concepts, practices and norms that nurture and enable model use and re-use across programs, projects and other complex endeavors. Key components include the ability to effectively move relevant information through a large community, process patterns that support model reuse and the identification of the necessary meta-information (ex. history, credibility, and provenance) to safely use and re-use that information. In order to successfully Use and Re-Use Models and Simulations we must define and meet key organizational and structural needs: 1. We must understand and acknowledge all the roles and players involved from the initial need identification through to the final product, as well as how they change across the lifecycle. 2. We must create the necessary structural elements to store and share NIMA-enabled information throughout the Program or Project lifecycle. 3. We must create the necessary organizational processes to stand up and execute a NIMA-enabled Program or Project throughout its lifecycle. NASA must meet all three of these needs to successfully use and re-use models. The ability to Reuse Models a key component of NIMA and the capabilities inherent in NIMA are key to accomplishing NASA's space exploration goals. 11

Manned remote work station development article. Volume 3: Development test plan. Appendix A: Manufacturing requirements/schedule

NASA Technical Reports Server (NTRS)

1979-01-01

The tests and procedures for the manned remote work station (MRWS) open cherry picker (OCP) development test article (DTA) are described to validate systems requirements and performance specifications. A development test program is outlined to evaluate key design issues and man/machine interfaces when the MRWS OCP is used in a shuttle support role of satellite servicing and in orbit construction of large structures.

Changes in Trace and Minor Constituents and Associated Micro-architecture of Montastrea faveolata during Time of Stress

DTIC Science & Technology

2003-09-01

activity of endosymbiotic dinoflagellates (commonly called zooxanthellae ) playing a major role. During biomineralization, the carbonate skeleton...precipitation of the carbonate structure driven by the photosynthetic zooxanthellae [16]. In the Looe Key corals, the δ13C ranges from –20/00 to –30/00...in the low density portion of the skeleton reflecting an influence of zooxanthellae photosynthesis. However, during the formation of the high

Shifting Stakes: Understanding the Dynamic Roles of Individuals and Organizations in Social Media Protests.

PubMed

Spiro, Emma S; Monroy-Hernández, Andrés

2016-01-01

In this paper we examine two protests characterized by substantial social media presence and distributed participation frameworks via two core questions: what roles did organizations and individuals play, and how did participants' social interactions change over the course of the protests? To answer these questions, we analyzed a large Twitter activity dataset for the #YoSoy132 student uprising in Mexico and Brazil's "bus rebellion." Results indicate that individuals initially took prominence at the protests but faded in importance as the movements dwindled and organizations took over. Regarding the dynamics and structure of the interactions, we found that key time points with unique social structures often map to exogenous events such as coordinated protests in physical locations. Our results have important consequences for the visibility of such social movements and their ability to attract continued participation by individuals and organizations.

Shifting Stakes: Understanding the Dynamic Roles of Individuals and Organizations in Social Media Protests

PubMed Central

2016-01-01

In this paper we examine two protests characterized by substantial social media presence and distributed participation frameworks via two core questions: what roles did organizations and individuals play, and how did participants’ social interactions change over the course of the protests? To answer these questions, we analyzed a large Twitter activity dataset for the #YoSoy132 student uprising in Mexico and Brazil’s “bus rebellion.” Results indicate that individuals initially took prominence at the protests but faded in importance as the movements dwindled and organizations took over. Regarding the dynamics and structure of the interactions, we found that key time points with unique social structures often map to exogenous events such as coordinated protests in physical locations. Our results have important consequences for the visibility of such social movements and their ability to attract continued participation by individuals and organizations. PMID:27776191

Dynamic hyper-editing underlies temperature adaptation in Drosophila

PubMed Central

Ashwal-Fluss, Reut; Pandey, Varun; Levanon, Erez Y.; Kadener, Sebastian

2017-01-01

In Drosophila, A-to-I editing is prevalent in the brain, and mutations in the editing enzyme ADAR correlate with specific behavioral defects. Here we demonstrate a role for ADAR in behavioral temperature adaptation in Drosophila. Although there is a higher level of editing at lower temperatures, at 29°C more sites are edited. These sites are less evolutionarily conserved, more disperse, less likely to be involved in secondary structures, and more likely to be located in exons. Interestingly, hypomorph mutants for ADAR display a weaker transcriptional response to temperature changes than wild-type flies and a highly abnormal behavioral response upon temperature increase. In sum, our data shows that ADAR is essential for proper temperature adaptation, a key behavior trait that is essential for survival of flies in the wild. Moreover, our results suggest a more general role of ADAR in regulating RNA secondary structures in vivo. PMID:28746393

Individuals and populations: the role of long-term, individual-based studies of animals in ecology and evolutionary biology.

PubMed

Clutton-Brock, Tim; Sheldon, Ben C

2010-10-01

Many important questions in ecology and evolutionary biology can only be answered with data that extend over several decades and answering a substantial proportion of questions requires records of the life histories of recognisable individuals. We identify six advantages that long-term, individual based studies afford in ecology and evolution: (i) analysis of age structure; (ii) linkage between life history stages; (iii) quantification of social structure; (iv) derivation of lifetime fitness measures; (v) replication of estimates of selection; (vi) linkage between generations, and we review their impact on studies in six key areas of evolution and ecology. Our review emphasises the unusual opportunities and productivity of long-term, individual-based studies and documents the important role that they play in research on ecology and evolutionary biology as well as the difficulties they face. Copyright © 2010 Elsevier Ltd. All rights reserved.

Structure and Bonding in Heme-Nitrosyl Complexes and Implications for Biology

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

Lehnert, Nicolai; Scheidt, W. Robert; Wolf, Matthew W.

This review summarizes our current understanding of the geometric and electronic structures of ferrous and ferric heme–nitrosyls, which are of key importance for the biological functions and transformations of NO. In-depth correlations are made between these properties and the reactivities of these species. Here, a focus is put on the discoveries that have been made in the last 10 years, but previous findings are also included as necessary. Besides this, ferrous heme–nitroxyl complexes are also considered, which have become of increasing interest recently due to their roles as intermediates in NO and multiheme nitrite reductases, and because of the potentialmore » role of HNO as a signaling molecule in mammals. In recent years, computational methods have received more attention as a means of investigating enzyme reaction mechanisms, and some important findings from these theoretical studies are also highlighted in this chapter.« less

Morphometric analysis of astrocytes in brainstem respiratory regions.

PubMed

Sheikhbahaei, Shahriar; Morris, Brian; Collina, Jared; Anjum, Sommer; Znati, Sami; Gamarra, Julio; Zhang, Ruli; Gourine, Alexander V; Smith, Jeffrey C

2018-06-11

Astrocytes, the most abundant and structurally complex glial cells of the central nervous system, are proposed to play an important role in modulating the activities of neuronal networks, including respiratory rhythm-generating circuits of the preBötzinger complex (preBötC) located in the ventrolateral medulla of the brainstem. However, structural properties of astrocytes residing within different brainstem regions are unknown. In this study astrocytes in the preBötC, an intermediate reticular formation (IRF) region with respiratory-related function, and a region of the nucleus tractus solitarius (NTS) in adult rats were reconstructed and their morphological features were compared. Detailed morphological analysis revealed that preBötC astrocytes are structurally more complex than those residing within the functionally distinct neighboring IRF region, or the NTS, located at the dorsal aspect of the medulla oblongata. Structural analyses of the brainstem microvasculature indicated no significant regional differences in vascular properties. We hypothesize that high morphological complexity of preBötC astrocytes reflects their functional role in providing structural/metabolic support and modulation of the key neuronal circuits essential for breathing, as well as constraints imposed by arrangements of associated neurons and/or other local structural features of the brainstem parenchyma. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Cardiolipin effects on membrane structure and dynamics.

PubMed

Unsay, Joseph D; Cosentino, Katia; Subburaj, Yamunadevi; García-Sáez, Ana J

2013-12-23

Cardiolipin (CL) is a lipid with unique properties solely found in membranes generating electrochemical potential. It contains four acyl chains and tends to form nonlamellar structures, which are believed to play a key role in membrane structure and function. Indeed, CL alterations have been linked to disorders such as Barth syndrome and Parkinson's disease. However, the molecular effects of CL on membrane organization remain poorly understood. Here, we investigated the structure and physical properties of CL-containing membranes using confocal microscopy, fluorescence correlation spectroscopy, and atomic force microscopy. We found that the fluidity of the lipid bilayer increased and its mechanical stability decreased with CL concentration, indicating that CL decreases the packing of the membrane. Although the presence of up to 20% CL gave rise to flat, stable bilayers, the inclusion of 5% CL promoted the formation of flowerlike domains that grew with time. Surprisingly, we often observed two membrane-piercing events in atomic force spectroscopy experiments with CL-containing membranes. Similar behavior was observed with a lipid mixture mimicking the mitochondrial outer membrane composition. This suggests that CL promotes the formation of membrane areas with apposed double bilayers or nonlamellar structures, similar to those proposed for mitochondrial contact sites. All together, we show that CL induces membrane alterations that support the role of CL in facilitating bilayer structure remodeling, deformation, and permeabilization.

2008 GRC Iron Sulfur Enzymes-Conference to be held June 8-13, 2008

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

Cramer, Stephen; Gray, Nancy Ryan

2009-01-01

Iron-sulfur proteins are among the most common and ancient enzymes and electron-transfer agents in nature. They play key roles in photosynthesis, respiration, and the metabolism of small molecules such as H2, CO, and N2. The Iron Sulfur Enzyme Gordon Research Conference evolved from an earlier GRC on Nitrogen Fixation that began in 1994. The scope of the current meeting has broadened to include all enzymes or metalloproteins in which Fe-S bonds play a key role. This year's meeting will focus on the biosynthesis of Fe-S clusters, as well as the structure and mechanism of key Fe-S enzymes such as hydrogenase,more » nitrogenase and its homologues, radical SAM enzymes, and aconitase-related enzymes. Recent progress on the role of Fe-S enzymes in health, disease, DNA/RNA-processing, and alternative bio-energy systems will also be highlighted. This conference will assemble a broad, diverse, and international group of biologists and chemists who are investigating fundamental issues related to Fe-S enzymes, on atomic, molecular, organism, and environmental scales. The topics to be addressed will include: Biosynthesis & Genomics of Fe-S Enzymes; Fundamental Fe-S Chemistry; Hydrogen and Fe-S Enzymes; Nitrogenase & Homologous Fe-S Enzymes; Fe-S Enzymes in Health & Disease; Radical SAM and Aconitase-Related Fe-S Enzymes; Fe-S Enzymes and Synthetic Analogues in BioEnergy; and Fe-S Enzymes in Geochemistry and the Origin of Life.« less

A novel enteric neuron–glia coculture system reveals the role of glia in neuronal development

PubMed Central

Le Berre‐Scoul, Catherine; Chevalier, Julien; Oleynikova, Elena; Cossais, François; Talon, Sophie; Neunlist, Michel

2016-01-01

Key points Unlike astrocytes in the brain, the potential role of enteric glial cells (EGCs) in the formation of the enteric neuronal circuit is currently unknown.To examine the role of EGCs in the formation of the neuronal network, we developed a novel neuron‐enriched culture model from embryonic rat intestine grown in indirect coculture with EGCs.We found that EGCs shape axonal complexity and synapse density in enteric neurons, through purinergic‐ and glial cell line‐derived neurotrophic factor‐dependent pathways.Using a novel and valuable culture model to study enteric neuron–glia interactions, our study identified EGCs as a key cellular actor regulating neuronal network maturation. Abstract In the nervous system, the formation of neuronal circuitry results from a complex and coordinated action of intrinsic and extrinsic factors. In the CNS, extrinsic mediators derived from astrocytes have been shown to play a key role in neuronal maturation, including dendritic shaping, axon guidance and synaptogenesis. In the enteric nervous system (ENS), the potential role of enteric glial cells (EGCs) in the maturation of developing enteric neuronal circuit is currently unknown. A major obstacle in addressing this question is the difficulty in obtaining a valuable experimental model in which enteric neurons could be isolated and maintained without EGCs. We adapted a cell culture method previously developed for CNS neurons to establish a neuron‐enriched primary culture from embryonic rat intestine which was cultured in indirect coculture with EGCs. We demonstrated that enteric neurons grown in such conditions showed several structural, phenotypic and functional hallmarks of proper development and maturation. However, when neurons were grown without EGCs, the complexity of the axonal arbour and the density of synapses were markedly reduced, suggesting that glial‐derived factors contribute strongly to the formation of the neuronal circuitry. We found that these effects played by EGCs were mediated in part through purinergic P2Y1 receptor‐ and glial cell line‐derived neurotrophic factor‐dependent pathways. Using a novel and valuable culture model to study enteric neuron–glia interactions, our study identified EGCs as a key cellular actor required for neuronal network maturation. PMID:27436013

Ideological and organizational components of differing public health strategies for addressing the social determinants of health.

PubMed

Raphael, Dennis; Brassolotto, Julia; Baldeo, Navindra

2015-12-01

Despite a history of conceptual contributions to reducing health inequalities by addressing the social determinants of health (SDH), Canadian governmental authorities have struggled to put these concepts into action. Ontario's-Canada's most populous province-public health scene shows a similar pattern. In statements and reports, governmental ministries, professional associations and local public health units (PHUs) recognize the importance of these issues, yet there has been varying implementation of these concepts into public health activity. The purpose of this study was to gain insight into the key features responsible for differences in SDH-related activities among local PHUs. We interviewed Medical Officers of Health (MOH) and key staff members from nine local PHUs in Ontario varying in SDH activity as to their understandings of the SDH, public health's role in addressing the SDH, and their units' SDH-related activities. We also reviewed their unit's documents and their organizational structures in relation to acting on the SDH. Three clusters of PHUs are identified based on their SDH-related activities: service-delivery-oriented; intersectoral and community-based; and public policy/public education-focused. The two key factors that differentiate PHUs are specific ideological commitments held by MOHs and staff and the organizational structures established to carry out SDH-related activities. The ideological commitments and the organizational structures of the most active PHUs showed congruence with frameworks adopted by national jurisdictions known for addressing health inequalities. These include a structural analysis of the SDH and a centralized organizational structure that coordinates SDH-related activities. © The Author (2014). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Apoptosis in lung injury and remodeling.

PubMed

Li, Xiaopeng; Shu, Ruijie; Filippatos, Gerasimos; Uhal, Bruce D

2004-10-01

The mode of cell death termed apoptosis, sometimes referred to as programmed cell death, is as critical a determinant of cell population size as is cell proliferation. Although best characterized in cells of the immune system, apoptosis is now known to be a key factor in the maintenance of normal cell turnover within structural cells in the parenchyma of virtually every organ. Recent interest in apoptosis in the lung has sparked a surge of investigations designed to determine the roles of apoptosis in lung development, injury, and remodeling. Of particular recent interest are the roles of apoptosis in disease pathogenesis and resolution, in which the concept of apoptosis as a "programmed" cell death, i.e., genetically determined, is often more accurately viewed as "inappropriate cell suicide" with regard to its extent and/or timing. Data accumulating over the past decade have made clear the complexity of the control of lung cell apoptosis; concepts of the regulation of apoptosis originally determined in classical cell culture models are often, but not always, applicable to structural cells. For this reason, each of the many cell types of the lung must be studied as a potentially new subject with its own idiosyncrasies yet to be discovered. In light of the large volume of literature now available, this article focuses on the roles of apoptosis in three pathophysiological contexts: acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary fibrosis. Each section presents key data describing the evidence for apoptosis in the lung, its possible relevance to disease pathogenesis, and proposed mechanisms that might suggest potential avenues for therapeutic intervention.

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.

Embryo mechanics: balancing force production with elastic resistance during morphogenesis.

PubMed

Davidson, Lance A

2011-01-01

Morphogenesis requires the spatial and temporal control of embryo mechanics, including force production and mechanical resistance to those forces, to coordinate tissue deformation and large-scale movements. Thus, biomechanical processes play a key role in directly shaping the embryo. Additional roles for embryo mechanics during development may include the patterning of positional information and to provide feedback to ensure the success of morphogenetic movements in shaping the larval body and organs. To understand the multiple roles of mechanics during development requires familiarity with engineering principles of the mechanics of structures, the viscoelastic properties of biomaterials, and the integration of force and stress within embryonic structures as morphogenesis progresses. In this chapter, we review the basic engineering principles of biomechanics as they relate to morphogenesis, introduce methods for quantifying embryo mechanics and the limitations of these methods, and outline a formalism for investigating the role of embryo mechanics in birth defects. We encourage the nascent field of embryo mechanics to adopt standard engineering terms and test methods so that studies of diverse organisms can be compared and universal biomechanical principles can be revealed. Copyright © 2011 Elsevier Inc. All rights reserved.

Mineral Types and Tree Species Determine the Functional and Taxonomic Structures of Forest Soil Bacterial Communities.

PubMed

Colin, Y; Nicolitch, O; Turpault, M-P; Uroz, S

2017-03-01

Although minerals represent important soil constituents, their impact on the diversity and structure of soil microbial communities remains poorly documented. In this study, pure mineral particles with various chemistries (i.e., obsidian, apatite, and calcite) were considered. Each mineral type was conditioned in mesh bags and incubated in soil below different tree stands (beech, coppice with standards, and Corsican pine) for 2.5 years to determine the relative impacts of mineralogy and mineral weatherability on the taxonomic and functional diversities of mineral-associated bacterial communities. After this incubation period, the minerals and the surrounding bulk soil were collected to determine mass loss and to perform soil analyses, enzymatic assays, and cultivation-dependent and -independent analyses. Notably, our 16S rRNA gene pyrosequencing analyses revealed that after the 2.5-year incubation period, the mineral-associated bacterial communities strongly differed from those of the surrounding bulk soil for all tree stands considered. When focusing only on minerals, our analyses showed that the bacterial communities associated with calcite, the less recalcitrant mineral type, significantly differed from those that colonized obsidian and apatite minerals. The cultivation-dependent analysis revealed significantly higher abundances of effective mineral-weathering bacteria on the most recalcitrant minerals (i.e., apatite and obsidian). Together, our data showed an enrichment of Betaproteobacteria and effective mineral-weathering bacteria related to the Burkholderia and Collimonas genera on the minerals, suggesting a key role for these taxa in mineral weathering and nutrient cycling in nutrient-poor forest ecosystems. IMPORTANCE Forests are usually developed on nutrient-poor and rocky soils, while nutrient-rich soils have been dedicated to agriculture. In this context, nutrient recycling and nutrient access are key processes in such environments. Deciphering how soil mineralogy influences the diversity, structure, and function of soil bacterial communities in relation to the soil conditions is crucial to better understanding the relative role of the soil bacterial communities in nutrient cycling and plant nutrition in nutrient-poor environments. The present study determined in detail the diversity and structure of bacterial communities associated with different mineral types incubated for 2.5 years in the soil under different tree species using cultivation-dependent and -independent analyses. Our data showed an enrichment of specific bacterial taxa on the minerals, specifically on the most weathered minerals, suggesting that they play key roles in mineral weathering and nutrient cycling in nutrient-poor forest ecosystems. Copyright © 2017 American Society for Microbiology.

Mineral Types and Tree Species Determine the Functional and Taxonomic Structures of Forest Soil Bacterial Communities

PubMed Central

Colin, Y.; Nicolitch, O.; Turpault, M.-P.

2016-01-01

ABSTRACT Although minerals represent important soil constituents, their impact on the diversity and structure of soil microbial communities remains poorly documented. In this study, pure mineral particles with various chemistries (i.e., obsidian, apatite, and calcite) were considered. Each mineral type was conditioned in mesh bags and incubated in soil below different tree stands (beech, coppice with standards, and Corsican pine) for 2.5 years to determine the relative impacts of mineralogy and mineral weatherability on the taxonomic and functional diversities of mineral-associated bacterial communities. After this incubation period, the minerals and the surrounding bulk soil were collected to determine mass loss and to perform soil analyses, enzymatic assays, and cultivation-dependent and -independent analyses. Notably, our 16S rRNA gene pyrosequencing analyses revealed that after the 2.5-year incubation period, the mineral-associated bacterial communities strongly differed from those of the surrounding bulk soil for all tree stands considered. When focusing only on minerals, our analyses showed that the bacterial communities associated with calcite, the less recalcitrant mineral type, significantly differed from those that colonized obsidian and apatite minerals. The cultivation-dependent analysis revealed significantly higher abundances of effective mineral-weathering bacteria on the most recalcitrant minerals (i.e., apatite and obsidian). Together, our data showed an enrichment of Betaproteobacteria and effective mineral-weathering bacteria related to the Burkholderia and Collimonas genera on the minerals, suggesting a key role for these taxa in mineral weathering and nutrient cycling in nutrient-poor forest ecosystems. IMPORTANCE Forests are usually developed on nutrient-poor and rocky soils, while nutrient-rich soils have been dedicated to agriculture. In this context, nutrient recycling and nutrient access are key processes in such environments. Deciphering how soil mineralogy influences the diversity, structure, and function of soil bacterial communities in relation to the soil conditions is crucial to better understanding the relative role of the soil bacterial communities in nutrient cycling and plant nutrition in nutrient-poor environments. The present study determined in detail the diversity and structure of bacterial communities associated with different mineral types incubated for 2.5 years in the soil under different tree species using cultivation-dependent and -independent analyses. Our data showed an enrichment of specific bacterial taxa on the minerals, specifically on the most weathered minerals, suggesting that they play key roles in mineral weathering and nutrient cycling in nutrient-poor forest ecosystems. PMID:28003192

Silk Self-Assembly Mechanisms and Control-From Thermodynamics to Kinetics

PubMed Central

Lu, Qiang; Zhu, Hesun; Zhang, Cencen; Zhang, Feng; Zhang, Bing; Kaplan, David L.

2012-01-01

Silkworms and spiders generate fibres that exhibit high strength and extensibility. The underlying mechanisms involved in processing silk proteins into fiber form remain incompletely understood, resulting in the failure to fully recapitulate the remarkable properties of native fibers in vitro from regenerated silk solutions. In the present study, the extensibility and high strength of regenerated silks were achieved by mimicking the natural spinning process. Conformational transitions inside micelles, followed by aggregation of micelles and their stabilization as they relate to the metastable structure of silk are described. Subsequently, the mechanisms to control the formation of nanofibrous structures were elucidated. The results clarify that the self-assembly of silk in aqueous solution is a thermodynamically driven process where kinetics also play a key role. Four key factors, molecular mobility, charge, hydrophilic interactions and concentration underlie the process. Adjusting these factors can balance nanostructure and conformational composition, and be used to achieve silk-based materials with properties comparable to native fibers. These mechanisms suggest new directions to design silk-based multifunctional materials. PMID:22320432

New tricks for the glycyl radical enzyme family

PubMed Central

Backman, Lindsey R.F.; Funk, Michael A.; Dawson, Christopher D.; Drennan, Catherine. L.

2018-01-01

Glycyl radical enzymes (GREs) are important biological catalysts in both strict and facultative anaerobes, playing key roles both in the human microbiota and in the environment. GREs contain a backbone glycyl radical that is post-translationally installed, enabling radical-based mechanisms. GREs function in several metabolic pathways including mixed acid fermentation, ribonucleotide reduction, and the anaerobic breakdown of the nutrient choline and the pollutant toluene. By generating a substrate-based radical species within the active site, GREs enable C-C, C-O, and C-N bond breaking and formation steps that are otherwise challenging for non-radical enzymes. Identification of previously unknown family members from genomic data and the determination of structures of well-characterized GREs have expanded the scope of GRE-catalyzed reactions as well as defined key features that enable radical catalysis. Here we review the structures and mechanisms of characterized GREs, classifying members into five categories. We consider the open questions about each of the five GRE classes and evaluate the tools available to interrogate uncharacterized GREs. PMID:28901199

New Insights into Perfluorinated Sulfonic-Acid Ionomers

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

Kusoglu, Ahmet; Weber, Adam Z.

In this comprehensive review, recent progress and developments on perfluorinated sulfonic-acid (PFSA) membranes have been summarized on many key topics. Although quite well investigated for decades, PFSA ionomers’ complex behavior, along with their key role in many emerging technologies, have presented significant scientific challenges but also helped create a unique cross-disciplinary research field to overcome such challenges. Research and progress on PFSAs, especially when considered with their applications, are at the forefront of bridging electrochemistry and polymer (physics), which have also opened up development of state-of-the-art in situ characterization techniques as well as multiphysics computation models. Topics reviewed stem frommore » correlating the various physical (e.g., mechanical) and transport properties with morphology and structure across time and length scales. In addition, topics of recent interest such as structure/transport correlations and modeling, composite PFSA membranes, degradation phenomena, and PFSA thin films are presented. Throughout, the impact of PFSA chemistry and side-chain is also discussed to present a broader perspective.« less

Kinetic control of block copolymer self-assembly into multicompartment and novel geometry nanoparticles

NASA Astrophysics Data System (ADS)

Chen, Yingchao; Wang, Xiaojun; Zhang, Ke; Wooley, Karen; Mays, Jimmy; Percec, Virgil; Pochan, Darrin

2012-02-01

Micelles with the segregation of hydrophobic blocks trapped in the same nanoparticle core have been produced through co-self-assembly of two block copolymers in THF/water dilute solution. The dissolution of two block copolymer sharing the same polyacrylic acid PAA blocks in THF undergoes consequent aggregation and phase separation through either slow water titration or quick water addition that triggers the micellar formation. The combination and comparison of the two water addition kinetic pathways are the keys of forming multicompartment structures at high water content. Importantly, the addition of organic diamine provides for acid-base complexation with the PAA side chains which, in turn, plays the key role of trapping unlike hydrophobic blocks from different block copolymers into one nanoparticle core. The kinetic control of solution assembly can be applied to other molecular systems such as dendrimers as well as other block copolymer molecules. Transmission electron microscopy, cryogenic transmission electron microscopy, light scattering have been applied to characterize the micelle structures.

Ecological Networks in Stored Grain: Key Postharvest Nodes for Emerging Pests, Pathogens, and Mycotoxins.

PubMed

Hernandez Nopsa, John F; Daglish, Gregory J; Hagstrum, David W; Leslie, John F; Phillips, Thomas W; Scoglio, Caterina; Thomas-Sharma, Sara; Walter, Gimme H; Garrett, Karen A

2015-10-01

Wheat is at peak quality soon after harvest. Subsequently, diverse biota use wheat as a resource in storage, including insects and mycotoxin-producing fungi. Transportation networks for stored grain are crucial to food security and provide a model system for an analysis of the population structure, evolution, and dispersal of biota in networks. We evaluated the structure of rail networks for grain transport in the United States and Eastern Australia to identify the shortest paths for the anthropogenic dispersal of pests and mycotoxins, as well as the major sources, sinks, and bridges for movement. We found important differences in the risk profile in these two countries and identified priority control points for sampling, detection, and management. An understanding of these key locations and roles within the network is a new type of basic research result in postharvest science and will provide insights for the integrated pest management of high-risk subpopulations, such as pesticide-resistant insect pests.

Ecological Networks in Stored Grain: Key Postharvest Nodes for Emerging Pests, Pathogens, and Mycotoxins

PubMed Central

Hernandez Nopsa, John F.; Daglish, Gregory J.; Hagstrum, David W.; Leslie, John F.; Phillips, Thomas W.; Scoglio, Caterina; Thomas-Sharma, Sara; Walter, Gimme H.; Garrett, Karen A.

2015-01-01

Wheat is at peak quality soon after harvest. Subsequently, diverse biota use wheat as a resource in storage, including insects and mycotoxin-producing fungi. Transportation networks for stored grain are crucial to food security and provide a model system for an analysis of the population structure, evolution, and dispersal of biota in networks. We evaluated the structure of rail networks for grain transport in the United States and Eastern Australia to identify the shortest paths for the anthropogenic dispersal of pests and mycotoxins, as well as the major sources, sinks, and bridges for movement. We found important differences in the risk profile in these two countries and identified priority control points for sampling, detection, and management. An understanding of these key locations and roles within the network is a new type of basic research result in postharvest science and will provide insights for the integrated pest management of high-risk subpopulations, such as pesticide-resistant insect pests. PMID:26955074

New Insights into Perfluorinated Sulfonic-Acid Ionomers

DOE PAGES

Kusoglu, Ahmet; Weber, Adam Z.

2017-01-23

In this comprehensive review, recent progress and developments on perfluorinated sulfonic-acid (PFSA) membranes have been summarized on many key topics. Although quite well investigated for decades, PFSA ionomers’ complex behavior, along with their key role in many emerging technologies, have presented significant scientific challenges but also helped create a unique cross-disciplinary research field to overcome such challenges. Research and progress on PFSAs, especially when considered with their applications, are at the forefront of bridging electrochemistry and polymer (physics), which have also opened up development of state-of-the-art in situ characterization techniques as well as multiphysics computation models. Topics reviewed stem frommore » correlating the various physical (e.g., mechanical) and transport properties with morphology and structure across time and length scales. In addition, topics of recent interest such as structure/transport correlations and modeling, composite PFSA membranes, degradation phenomena, and PFSA thin films are presented. Throughout, the impact of PFSA chemistry and side-chain is also discussed to present a broader perspective.« less

Structure of a eukaryotic SWEET transporter in a homotrimeric complex.

PubMed

Tao, Yuyong; Cheung, Lily S; Li, Shuo; Eom, Joon-Seob; Chen, Li-Qing; Xu, Yan; Perry, Kay; Frommer, Wolf B; Feng, Liang

2015-11-12

Eukaryotes rely on efficient distribution of energy and carbon skeletons between organs in the form of sugars. Glucose in animals and sucrose in plants serve as the dominant distribution forms. Cellular sugar uptake and release require vesicular and/or plasma membrane transport proteins. Humans and plants use proteins from three superfamilies for sugar translocation: the major facilitator superfamily (MFS), the sodium solute symporter family (SSF; only in the animal kingdom), and SWEETs. SWEETs carry mono- and disaccharides across vacuolar or plasma membranes. Plant SWEETs play key roles in sugar translocation between compartments, cells, and organs, notably in nectar secretion, phloem loading for long distance translocation, pollen nutrition, and seed filling. Plant SWEETs cause pathogen susceptibility possibly by sugar leakage from infected cells. The vacuolar Arabidopsis thaliana AtSWEET2 sequesters sugars in root vacuoles; loss-of-function mutants show increased susceptibility to Pythium infection. Here we show that its orthologue, the vacuolar glucose transporter OsSWEET2b from rice (Oryza sativa), consists of an asymmetrical pair of triple-helix bundles, connected by an inversion linker transmembrane helix (TM4) to create the translocation pathway. Structural and biochemical analyses show OsSWEET2b in an apparent inward (cytosolic) open state forming homomeric trimers. TM4 tightly interacts with the first triple-helix bundle within a protomer and mediates key contacts among protomers. Structure-guided mutagenesis of the close paralogue SWEET1 from Arabidopsis identified key residues in substrate translocation and protomer crosstalk. Insights into the structure-function relationship of SWEETs are valuable for understanding the transport mechanism of eukaryotic SWEETs and may be useful for engineering sugar flux.

SWEETs, transporters for intracellular and intercellular sugar translocation.

PubMed

Eom, Joon-Seob; Chen, Li-Qing; Sosso, Davide; Julius, Benjamin T; Lin, I W; Qu, Xiao-Qing; Braun, David M; Frommer, Wolf B

2015-06-01

Three families of transporters have been identified as key players in intercellular transport of sugars: MSTs (monosaccharide transporters), SUTs (sucrose transporters) and SWEETs (hexose and sucrose transporters). MSTs and SUTs fall into the major facilitator superfamily; SWEETs constitute a structurally different class of transporters with only seven transmembrane spanning domains. The predicted topology of SWEETs is supported by crystal structures of bacterial homologs (SemiSWEETs). On average, angiosperm genomes contain ∼20 paralogs, most of which serve distinct physiological roles. In Arabidopsis, AtSWEET8 and 13 feed the pollen; SWEET11 and 12 provide sucrose to the SUTs for phloem loading; AtSWEET11, 12 and 15 have distinct roles in seed filling; AtSWEET16 and 17 are vacuolar hexose transporters; and SWEET9 is essential for nectar secretion. The remaining family members await characterization, and could play roles in the gametophyte as well as other important roles in sugar transport in the plant. In rice and cassava, and possibly other systems, sucrose transporting SWEETs play central roles in pathogen resistance. Notably, the human genome also contains a glucose transporting isoform. Further analysis promises new insights into mechanism and regulation of assimilate allocation and a new potential for increasing crop yield. Copyright © 2015 Elsevier Ltd. All rights reserved.

The social brain in psychiatric and neurological disorders

PubMed Central

Kennedy, Daniel P.; Adolphs, Ralph

2013-01-01

Psychiatric and neurological disorders have historically provided key insights into the structure-function relationships that subserve human social cognition and behavior, informing the concept of the ‘social brain’. In this review, we take stock of the current status of this concept, retaining a focus on disorders that impact social behavior. We discuss how the social brain, social cognition, and social behavior are interdependent, and emphasize the important role of development and compensation. We suggest that the social brain, and its dysfunction and recovery, must be understood not in terms of specific structures, but rather in terms of their interaction in large-scale networks. PMID:23047070

Predicting the Structure of the Solar Corona During the December 4, 2002 Total Solar Eclipse

NASA Technical Reports Server (NTRS)

Mikic, Zoran; Linker, Jon A.; Riley, Pete; Lionello, Roberto

2003-01-01

The solar magnetic field plays a key role in determining coronal. The principal input to MHD models is the observed solar magnetic field. 3D MHD models can be used to compare with eclipse and coronograph images, SOHO images (LOSCO, EIT), Ulysses and WIND spacecraft data, and interplanetary scintillation (IPS) measurements. MHD computations can tell us about the structure of the corona. Eclipses can help us to verify the accuracy of the models. 4 December, 2002 total eclipce: visible in the southern hemisphere (South Atlantic, southern Africa, Indian Ocean, and Australia). Total in center Angola is at 06:00 UT.

Proton-conducting ionic liquid-based Proton Exchange Membrane Fuel Cell membranes: The key role of ionomer-ionic liquid interaction

NASA Astrophysics Data System (ADS)

Martinez, Mathieu; Molmeret, Yannick; Cointeaux, Laure; Iojoiu, Cristina; Leprêtre, Jean-Claude; El Kissi, Nadia; Judeinstein, Patrick; Sanchez, Jean-Yves

The paper deals with the synthesis and characterisation of proton-conducting ionic liquids (PCILs) and their polymer electrolytes obtained by blending modified Nafion membranes with different concentrations of PCILs. The PCILs are obtained by the neutralization of triethylamine with different organic acids. The first part of the paper studies the influence of acidity and acid structure on PCIL thermal and electrochemical performance, while the second part examines membrane conductivity and reveals it to depend more on PCIL structure than on its intrinsic conductivity. At 130 °C, conductivities exceeding 10 mS cm -1 were obtained in fully anhydrous conditions.

Femtosecond diffraction dynamics of laser-induced periodic surface structures on fused silica

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

Hoehm, S.; Rosenfeld, A.; Krueger, J.

2013-02-04

The formation of laser-induced periodic surface structures (LIPSS) on fused silica upon irradiation with linearly polarized fs-laser pulses (50 fs pulse duration, 800 nm center wavelength) is studied experimentally using a transillumination femtosecond time-resolved (0.1 ps-1 ns) pump-probe diffraction approach. This allows to reveal the generation dynamics of near-wavelength-sized LIPSS showing a transient diffraction at specific spatial frequencies even before a corresponding permanent surface relief was observed. The results confirm that the ultrafast energy deposition to the materials surface plays a key role and triggers subsequent physical mechanisms such as carrier scattering into self-trapped excitons.

View of the bacterial strains of Escherichia coli M-17 and its interaction with the nanoparticles of zinc oxide by means of atomic force microscopy

NASA Astrophysics Data System (ADS)

Sagitova, A.; Yaminsky, I.; Meshkov, G.

2016-08-01

Visualization of the structure of biological objects plays a key role in medicine, biotechnology, nanotechnology and IT-technology. Atomic force microscopy (AFM) is a promising method of studying of objects’ morphology and structure. In this work, AFM was used to determine the size and shape of the bacterial strains of Escherichia coli M-17 and visualization its interaction with the nanoparticles of zinc oxide. The suspension of E.coli bacteria was applied to natural mica and studied by contact mode using the FemtoScan multifunctional scanning probe microscope.

Novel therapeutic strategies targeting fibroblasts and fibrosis in heart disease

PubMed Central

Gourdie, Robert G.; Dimmeler, Stefanie; Kohl, Peter

2016-01-01

Our understanding of cardiac fibroblast functions has moved beyond their roles in heart structure and extracellular matrix generation, and now includes contributions to paracrine, mechanical and electrical signalling during ontogenesis and normal cardiac activity. Fibroblasts have central roles in pathogenic remodelling during myocardial ischaemia, hypertension and heart failure. As key contributors to scar formation, they are crucial for tissue repair after interventions including surgery and ablation. Novel experimental approaches targeting cardiac fibroblasts are promising potential therapies for heart disease. Indeed, several existing drugs act, at least partially, through effects on cardiac connective tissue. This Review outlines the origins and roles of fibroblasts in cardiac development, homeostasis and disease; illustrates the involvement of fibroblasts in current and emerging clinical interventions; and identifies future targets for research and development. PMID:27339799

Rclick: a web server for comparison of RNA 3D structures.

PubMed

Nguyen, Minh N; Verma, Chandra

2015-03-15

RNA molecules play important roles in key biological processes in the cell and are becoming attractive for developing therapeutic applications. Since the function of RNA depends on its structure and dynamics, comparing and classifying the RNA 3D structures is of crucial importance to molecular biology. In this study, we have developed Rclick, a web server that is capable of superimposing RNA 3D structures by using clique matching and 3D least-squares fitting. Our server Rclick has been benchmarked and compared with other popular servers and methods for RNA structural alignments. In most cases, Rclick alignments were better in terms of structure overlap. Our server also recognizes conformational changes between structures. For this purpose, the server produces complementary alignments to maximize the extent of detectable similarity. Various examples showcase the utility of our web server for comparison of RNA, RNA-protein complexes and RNA-ligand structures. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

DoDLive | Department of Defense Blog

Science.gov Websites

her surgical career and her marriage to a Navy chief. Surgeon and Spouse: How One Navy Wife Balances Memorial Day Deal Legacy Mentors Play Key Role In TAPS Good Grief Camps Legacy mentors at the Memorial Day themselves. Legacy Mentors Play Key Role In TAPS Good Grief Camps Legacy Mentors Play Key Role In TAPS Good

Leadership in complex networks: the importance of network position and strategic action in a translational cancer research network.

PubMed

Long, Janet C; Cunningham, Frances C; Wiley, Janice; Carswell, Peter; Braithwaite, Jeffrey

2013-10-11

Leadership behaviour in complex networks is under-researched, and little has been written concerning leadership of translational research networks (TRNs) that take discoveries made 'at the bench' and translate them into practices used 'at the bedside.' Understanding leaders' opportunities and behaviours within TRNs working to solve this key problem in implementing evidence into clinical practice is therefore important. This study explored the network position of governing body members and perceptions of their role in a new TRN in Sydney, Australia. The paper asks three questions: Firstly, do the formal, mandated leaders of this TRN hold key positions of centrality or brokerage in the informal social network of collaborative ties? Secondly, if so, do they recognise the leadership opportunities that their network positions afford them? Thirdly, what activities associated with these key roles do they believe will maximise the TRN's success? Semi-structured interviews of all 14 governing body members conducted in early 2012 explored perceptions of their roles and sought comments on a list of activities drawn from review of successful transdisciplinary collaboratives combined with central and brokerage roles. An on-line, whole network survey of all 68 TRN members sought to understand and map existing collaborative connections. Leaders' positions in the network were assessed using UCInet, and graphs were generated in NetDraw. Social network analysis identified that governing body members had high centrality and high brokerage potential in the informal network of work-related ties. Interviews showed perceived challenges including 'silos' and the mismatch between academic and clinical goals of research. Governing body members recognised their central positions, which would facilitate the leadership roles of leading, making decisions, and providing expert advice necessary for the co-ordination of effort and relevant input across domains. Brokerage potential was recognised in their clearly understood role of representing a specialty, campus or research group on the governing body to provide strategic linkages. Facilitation, mentoring and resolving conflicts within more localised project teams were spoken of as something 'we do all the time anyway,' as well as something they would do if called upon. These leadership roles are all linked with successful collaborative endeavours in other fields. This paper links the empirical findings of the social network analysis with the qualitative findings of the interviews to show that the leaders' perceptions of their roles accord with both the potential inherent in their network positions as well as actual activities known to increase the success of transdisciplinary teams. Understanding this is key to successful TRNs.

Characterizing the structural ensemble of γ-secretase using a multiscale molecular dynamics approach† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc00980a Click here for additional data file.

PubMed Central

Aguayo-Ortiz, Rodrigo; Chávez-García, Cecilia; Straub, John E.

2017-01-01

γ-Secretase is an intramembrane-cleaving aspartyl protease that plays an essential role in the processing of a variety of integral membrane proteins. Its role in the ultimate cleavage step in the processing of amyloid precursor protein to form amyloid-β (Aβ) peptide makes it an important therapeutic target in Alzheimer's disease research. Significant recent advances have been made in structural studies of this critical membrane protein complex. However, details of the mechanism of activation of the enzyme complex remain unclear. Using a multiscale computational modeling approach, combining multiple coarse-grained microsecond dynamic trajectories with all-atom models, the structure and two conformational states of the γ-secretase complex were evaluated. The transition between enzymatic state 1 and state 2 is shown to critically depend on the protonation states of the key catalytic residues Asp257 and Asp385 in the active site domain. The active site formation, related to our γ-secretase state 2, is observed to involve a concerted movement of four transmembrane helices from the catalytic subunit, resulting in the required localization of the catalytic residues. Global analysis of the structural ensemble of the enzyme complex was used to identify collective fluctuations important to the mechanism of substrate recognition and demonstrate that the corresponding fluctuations observed were uncorrelated with structural changes associated with enzyme activation. Overall, this computational study provides essential insight into the role of structure and dynamics in the activation and function of γ-secretase. PMID:28970936

Patterns of population structure and dispersal in the long-lived "redwood" of the coral reef, the giant barrel sponge ( Xestospongia muta)

NASA Astrophysics Data System (ADS)

Richards, Vincent P.; Bernard, Andrea M.; Feldheim, Kevin A.; Shivji, Mahmood S.

2016-09-01

Sponges are one of the dominant fauna on Florida and Caribbean coral reefs, with species diversity often exceeding that of scleractinian corals. Despite the key role of sponges as structural components, habitat providers, and nutrient recyclers in reef ecosystems, their dispersal dynamics are little understood. We used ten microsatellite markers to study the population structure and dispersal patterns of a prominent reef species, the giant barrel sponge ( Xestospongia muta), the long-lived "redwood" of the reef, throughout Florida and the Caribbean. F-statistics, exact tests of population differentiation, and Bayesian multi-locus genotype analyses revealed high levels of overall genetic partitioning ( F ST = 0.12, P = 0.001) and grouped 363 individuals collected from the Bahamas, Honduras, US Virgin Islands, Key Largo (Florida), and the remainder of the Florida reef tract into at minimum five genetic clusters ( K = 5). Exact tests, however, revealed further differentiation, grouping sponges sampled from five locations across the Florida reef tract (~250 km) into three populations, suggesting a total of six genetic populations across the eight locations sampled. Assignment tests showed dispersal over ecological timescales to be limited to relatively short distances, as the only migration detected among populations was within the Florida reef tract. Consequently, populations of this major coral reef benthic constituent appear largely self-recruiting. A combination of levels of genetic differentiation, genetic distance, and assignment tests support the important role of the Caribbean and Florida currents in shaping patterns of contemporary and historical gene flow in this widespread coral reef species.

Network analyses based on comprehensive molecular interaction maps reveal robust control structures in yeast stress response pathways

PubMed Central

Kawakami, Eiryo; Singh, Vivek K; Matsubara, Kazuko; Ishii, Takashi; Matsuoka, Yukiko; Hase, Takeshi; Kulkarni, Priya; Siddiqui, Kenaz; Kodilkar, Janhavi; Danve, Nitisha; Subramanian, Indhupriya; Katoh, Manami; Shimizu-Yoshida, Yuki; Ghosh, Samik; Jere, Abhay; Kitano, Hiroaki

2016-01-01

Cellular stress responses require exquisite coordination between intracellular signaling molecules to integrate multiple stimuli and actuate specific cellular behaviors. Deciphering the web of complex interactions underlying stress responses is a key challenge in understanding robust biological systems and has the potential to lead to the discovery of targeted therapeutics for diseases triggered by dysregulation of stress response pathways. We constructed large-scale molecular interaction maps of six major stress response pathways in Saccharomyces cerevisiae (baker’s or budding yeast). Biological findings from over 900 publications were converted into standardized graphical formats and integrated into a common framework. The maps are posted at http://www.yeast-maps.org/yeast-stress-response/ for browse and curation by the research community. On the basis of these maps, we undertook systematic analyses to unravel the underlying architecture of the networks. A series of network analyses revealed that yeast stress response pathways are organized in bow–tie structures, which have been proposed as universal sub-systems for robust biological regulation. Furthermore, we demonstrated a potential role for complexes in stabilizing the conserved core molecules of bow–tie structures. Specifically, complex-mediated reversible reactions, identified by network motif analyses, appeared to have an important role in buffering the concentration and activity of these core molecules. We propose complex-mediated reactions as a key mechanism mediating robust regulation of the yeast stress response. Thus, our comprehensive molecular interaction maps provide not only an integrated knowledge base, but also a platform for systematic network analyses to elucidate the underlying architecture in complex biological systems. PMID:28725465

Substrate Type and Free Ammonia Determine Bacterial Community Structure in Full-Scale Mesophilic Anaerobic Digesters Treating Cattle or Swine Manure.

PubMed

Li, Jiabao; Rui, Junpeng; Yao, Minjie; Zhang, Shiheng; Yan, Xuefeng; Wang, Yuanpeng; Yan, Zhiying; Li, Xiangzhen

2015-01-01

The microbial-mediated anaerobic digestion (AD) process represents an efficient biological process for the treatment of organic waste along with biogas harvest. Currently, the key factors structuring bacterial communities and the potential core and unique bacterial populations in manure anaerobic digesters are not completely elucidated yet. In this study, we collected sludge samples from 20 full-scale anaerobic digesters treating cattle or swine manure, and investigated the variations of bacterial community compositions using high-throughput 16S rRNA amplicon sequencing. Clustering and correlation analysis suggested that substrate type and free ammonia (FA) play key roles in determining the bacterial community structure. The COD: [Formula: see text] (C:N) ratio of substrate and FA were the most important available operational parameters correlating to the bacterial communities in cattle and swine manure digesters, respectively. The bacterial populations in all of the digesters were dominated by phylum Firmicutes, followed by Bacteroidetes, Proteobacteria and Chloroflexi. Increased FA content selected Firmicutes, suggesting that they probably play more important roles under high FA content. Syntrophic metabolism by Proteobacteria, Chloroflexi, Synergistetes and Planctomycetes are likely inhibited when FA content is high. Despite the different manure substrates, operational conditions and geographical locations of digesters, core bacterial communities were identified. The core communities were best characterized by phylum Firmicutes, wherein Clostridium predominated overwhelmingly. Substrate-unique and abundant communities may reflect the properties of manure substrate and operational conditions. These findings extend our current understanding of the bacterial assembly in full-scale manure anaerobic digesters.

Substrate Type and Free Ammonia Determine Bacterial Community Structure in Full-Scale Mesophilic Anaerobic Digesters Treating Cattle or Swine Manure

PubMed Central

Li, Jiabao; Rui, Junpeng; Yao, Minjie; Zhang, Shiheng; Yan, Xuefeng; Wang, Yuanpeng; Yan, Zhiying; Li, Xiangzhen

2015-01-01

The microbial-mediated anaerobic digestion (AD) process represents an efficient biological process for the treatment of organic waste along with biogas harvest. Currently, the key factors structuring bacterial communities and the potential core and unique bacterial populations in manure anaerobic digesters are not completely elucidated yet. In this study, we collected sludge samples from 20 full-scale anaerobic digesters treating cattle or swine manure, and investigated the variations of bacterial community compositions using high-throughput 16S rRNA amplicon sequencing. Clustering and correlation analysis suggested that substrate type and free ammonia (FA) play key roles in determining the bacterial community structure. The COD: NH4+-N (C:N) ratio of substrate and FA were the most important available operational parameters correlating to the bacterial communities in cattle and swine manure digesters, respectively. The bacterial populations in all of the digesters were dominated by phylum Firmicutes, followed by Bacteroidetes, Proteobacteria and Chloroflexi. Increased FA content selected Firmicutes, suggesting that they probably play more important roles under high FA content. Syntrophic metabolism by Proteobacteria, Chloroflexi, Synergistetes and Planctomycetes are likely inhibited when FA content is high. Despite the different manure substrates, operational conditions and geographical locations of digesters, core bacterial communities were identified. The core communities were best characterized by phylum Firmicutes, wherein Clostridium predominated overwhelmingly. Substrate-unique and abundant communities may reflect the properties of manure substrate and operational conditions. These findings extend our current understanding of the bacterial assembly in full-scale manure anaerobic digesters. PMID:26648921

Striking Plasticity of CRISPR-Cas9 and Key Role of Non-target DNA, as Revealed by Molecular Simulations.

PubMed

Palermo, Giulia; Miao, Yinglong; Walker, Ross C; Jinek, Martin; McCammon, J Andrew

2016-10-26

The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system recently emerged as a transformative genome-editing technology that is innovating basic bioscience and applied medicine and biotechnology. The endonuclease Cas9 associates with a guide RNA to match and cleave complementary sequences in double stranded DNA, forming an RNA:DNA hybrid and a displaced non-target DNA strand. Although extensive structural studies are ongoing, the conformational dynamics of Cas9 and its interplay with the nucleic acids during association and DNA cleavage are largely unclear. Here, by employing multi-microsecond time scale molecular dynamics, we reveal the conformational plasticity of Cas9 and identify key determinants that allow its large-scale conformational changes during nucleic acid binding and processing. We show how the "closure" of the protein, which accompanies nucleic acid binding, fundamentally relies on highly coupled and specific motions of the protein domains, collectively initiating the prominent conformational changes needed for nucleic acid association. We further reveal a key role of the non-target DNA during the process of activation of the nuclease HNH domain, showing how the nontarget DNA positioning triggers local conformational changes that favor the formation of a catalytically competent Cas9. Finally, a remarkable conformational plasticity is identified as an intrinsic property of the HNH domain, constituting a necessary element that allows for the HNH repositioning. These novel findings constitute a reference for future experimental studies aimed at a full characterization of the dynamic features of the CRISPR-Cas9 system, and-more importantly-call for novel structure engineering efforts that are of fundamental importance for the rational design of new genome-engineering applications.

Crystal Structures of Beta- and Gammaretrovirus Fusion Proteins Reveal a Role for Electrostatic Stapling in Viral Entry

PubMed Central

Aydin, Halil; Cook, Jonathan D.

2014-01-01

Membrane fusion is a key step in the life cycle of all envelope viruses, but this process is energetically unfavorable; the transmembrane fusion subunit (TM) of the virion-attached glycoprotein actively catalyzes the membrane merger process. Retroviral glycoproteins are the prototypical system to study pH-independent viral entry. In this study, we determined crystal structures of extramembrane regions of the TMs from Mason-Pfizer monkey virus (MPMV) and xenotropic murine leukemia virus-related virus (XMRV) at 1.7-Å and 2.2-Å resolution, respectively. The structures are comprised of a trimer of hairpins that is characteristic of class I viral fusion proteins and now completes a structural library of retroviral fusion proteins. Our results allowed us to identify a series of intra- and interchain electrostatic interactions in the heptad repeat and chain reversal regions. Mutagenesis reveals that charge-neutralizing salt bridge mutations significantly destabilize the postfusion six-helix bundle and abrogate retroviral infection, demonstrating that electrostatic stapling of the fusion subunit is essential for viral entry. Our data indicate that salt bridges are a major stabilizing force on the MPMV and XMRV retroviral TMs and likely provide the key energetics for viral and host membrane fusion. PMID:24131724

Evolution of the Plant Reproduction Master Regulators LFY and the MADS Transcription Factors: The Role of Protein Structure in the Evolutionary Development of the Flower.

PubMed

Silva, Catarina S; Puranik, Sriharsha; Round, Adam; Brennich, Martha; Jourdain, Agnès; Parcy, François; Hugouvieux, Veronique; Zubieta, Chloe

2015-01-01

Understanding the evolutionary leap from non-flowering (gymnosperms) to flowering (angiosperms) plants and the origin and vast diversification of the floral form has been one of the focuses of plant evolutionary developmental biology. The evolving diversity and increasing complexity of organisms is often due to relatively small changes in genes that direct development. These "developmental control genes" and the transcription factors (TFs) they encode, are at the origin of most morphological changes. TFs such as LEAFY (LFY) and the MADS-domain TFs act as central regulators in key developmental processes of plant reproduction including the floral transition in angiosperms and the specification of the male and female organs in both gymnosperms and angiosperms. In addition to advances in genome wide profiling and forward and reverse genetic screening, structural techniques are becoming important tools in unraveling TF function by providing atomic and molecular level information that was lacking in purely genetic approaches. Here, we summarize previous structural work and present additional biophysical and biochemical studies of the key master regulators of plant reproduction - LEAFY and the MADS-domain TFs SEPALLATA3 and AGAMOUS. We discuss the impact of structural biology on our understanding of the complex evolutionary process leading to the development of the bisexual flower.

A one-dimensional ice structure built from pentagons

NASA Astrophysics Data System (ADS)

Carrasco, Javier; Michaelides, Angelos; Forster, Matthew; Haq, Sam; Raval, Rasmita; Hodgson, Andrew

2009-05-01

Heterogeneous ice nucleation has a key role in fields as diverse as atmospheric chemistry and biology. Ice nucleation on metal surfaces affords an opportunity to watch this process unfold at the molecular scale on a well-defined, planar interface. A common feature of structural models for such films is that they are built from hexagonal arrangements of molecules. Here we show, through a combination of scanning tunnelling microscopy, infrared spectroscopy and density-functional theory, that about 1-nm-wide ice chains that nucleate on Cu(110) are not built from hexagons, but instead are built from a face-sharing arrangement of water pentagons. The pentagon structure is favoured over others because it maximizes the water-metal bonding while maintaining a strong hydrogen-bonding network. It reveals an unanticipated structural adaptability of water-ice films, demonstrating that the presence of the substrate can be sufficient to favour non-hexagonal structural units.

Ventromedial Hypothalamus and the Generation of Aggression

PubMed Central

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

2017-01-01

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

Uncovering the role of the insula in non-motor symptoms of Parkinson’s disease

PubMed Central

Christopher, Leigh; Koshimori, Yuko; Lang, Anthony E.; Criaud, Marion

2014-01-01

Patients with Parkinson’s disease experience a range of non-motor symptoms, including cognitive impairment, behavioural changes, somatosensory and autonomic disturbances. The insula, which was once thought to be primarily a limbic cortical structure, is now known to be highly involved in integrating somatosensory, autonomic and cognitive-affective information to guide behaviour. Thus, it acts as a central hub for processing relevant information related to the state of the body as well as cognitive and mood states. Despite these crucial functions, the insula has been largely overlooked as a potential key region in contributing to non-motor symptoms of Parkinson’s disease. The insula is affected in Parkinson’s disease by alpha-synuclein deposition, disruptions in normal neurotransmitter function, alterations in connectivity as well as metabolic and structural changes. Although research focusing on the role of the insula in Parkinson’s disease is scarce, there is evidence from neuroimaging studies linking the insula to cognitive decline, behavioural abnormalities and somatosensory disturbances. Here, we review imaging studies that provide insight into the potential role of the insula in Parkinson’s disease non-motor symptoms. PMID:24736308

Membrane-Mediated Oligomerization of G Protein Coupled Receptors and Its Implications for GPCR Function

PubMed Central

Gahbauer, Stefan; Böckmann, Rainer A.

2016-01-01

The dimerization or even oligomerization of G protein coupled receptors (GPCRs) causes ongoing, controversial debates about its functional role and the coupled biophysical, biochemical or biomedical implications. A continously growing number of studies hints to a relation between oligomerization and function of GPCRs and strengthens the assumption that receptor assembly plays a key role in the regulation of protein function. Additionally, progress in the structural analysis of GPCR-G protein and GPCR-ligand interactions allows to distinguish between actively functional and non-signaling complexes. Recent findings further suggest that the surrounding membrane, i.e., its lipid composition may modulate the preferred dimerization interface and as a result the abundance of distinct dimeric conformations. In this review, the association of GPCRs and the role of the membrane in oligomerization will be discussed. An overview of the different reported oligomeric interfaces is provided and their capability for signaling discussed. The currently available data is summarized with regard to the formation of GPCR oligomers, their structures and dependency on the membrane microenvironment as well as the coupling of oligomerization to receptor function. PMID:27826255

Intrinsic motions in the N-terminal domain of an ionotropic glutamate receptor detected by fluorescence correlation spectroscopy.

PubMed

Jensen, Mette H; Sukumaran, Madhav; Johnson, Christopher M; Greger, Ingo H; Neuweiler, Hannes

2011-11-18

Ionotropic glutamate receptors (iGluRs) mediate excitatory neurotransmission in the central nervous system and play key roles in brain development and disease. iGluRs have two distinct extracellular domains, but the functional role of the distal N-terminal domain (NTD) is poorly understood. Crystal structures of the NTD from some non-N-methyl-d-aspartate (NMDA) iGluRs are consistent with a rigid body that facilitates receptor assembly but suggest an additional dynamic role that could modulate signaling. Here, we moved beyond spatial and temporal limitations of conventional protein single-molecule spectroscopy by employing correlation analysis of extrinsic oxazine fluorescence fluctuations. We observed nanosecond (ns)-to-microsecond (μs) motions of loop segments and helices within a region of an AMPA-type iGluR NTD, which has been identified previously to be structurally variable. Our data reveal that the AMPA receptor NTD undergoes rapid conformational fluctuations, suggesting an inherent allosteric capacity for this domain in addition to its established assembly function. Copyright © 2011 Elsevier Ltd. All rights reserved.

Pricing in health care organizations. A key component of the marketing mix.

PubMed

Marlowe, D

1989-01-01

Pricing is one of the key components of a successful marketing mix. Pricing objectives, strategies, and tactics cannot stand alone, however. To be effective, price must work in harmony with other marketing and management activities. Despite its importance, use of pricing as a management tool is limited in health care compared to other industries. Many factors contribute to this situation, including the structure of the health-care exchange process, limited consumer knowledge, and a limited ability to measure costs. I will provide an overview of pricing information, both within and outside health care. Specifically, we will explore the definition of pricing, nonmonetary pricing, price elasticity, classical pricing theory, and the role of pricing in a health-care setting.

A Theorem on the Rank of a Product of Matrices with Illustration of Its Use in Goodness of Fit Testing.

PubMed

Satorra, Albert; Neudecker, Heinz

2015-12-01

This paper develops a theorem that facilitates computing the degrees of freedom of Wald-type chi-square tests for moment restrictions when there is rank deficiency of key matrices involved in the definition of the test. An if and only if (iff) condition is developed for a simple rule of difference of ranks to be used when computing the desired degrees of freedom of the test. The theorem is developed exploiting basics tools of matrix algebra. The theorem is shown to play a key role in proving the asymptotic chi-squaredness of a goodness of fit test in moment structure analysis, and in finding the degrees of freedom of this chi-square statistic.

Use of health information technology to advance evidence-based care: lessons from the VA QUERI program.

PubMed

Hynes, Denise M; Weddle, Timothy; Smith, Nina; Whittier, Erika; Atkins, David; Francis, Joseph

2010-01-01

As the Department of Veterans Affairs (VA) Health Services Research and Development Service's Quality Enhancement Research Initiative (QUERI) has progressed, health information technology (HIT) has occupied a crucial role in implementation research projects. We evaluated the role of HIT in VA QUERI implementation research, including HIT use and development, the contributions implementation research has made to HIT development, and HIT-related barriers and facilitators to implementation research. Key informants from nine disease-specific QUERI Centers. Documentation analysis of 86 implementation project abstracts followed up by semi-structured interviews with key informants from each of the nine QUERI centers. We used qualitative and descriptive analyses. We found: (1) HIT provided data and information to facilitate implementation research, (2) implementation research helped to further HIT development in a variety of uses including the development of clinical decision support systems (23 of 86 implementation research projects), and (3) common HIT barriers to implementation research existed but could be overcome by collaborations with clinical and administrative leadership. Our review of the implementation research progress in the VA revealed interdependency on an HIT infrastructure and research-based development. Collaboration with multiple stakeholders is a key factor in successful use and development of HIT in implementation research efforts and in advancing evidence-based practice.

A qualitative study exploring physicians’ perceptions on the role of community pharmacists in Dubai

PubMed Central

2016-01-01

Objective: The aim of this study is to explore the perceptions of physicians operating within the boundaries of Dubai on the role of community pharmacists. Methods: Semi-structured interviews were done with 12 physicians working within the boundaries of Dubai Health Authority. Interviews mainly focused on understanding the perceptions of physicians on the role of community pharmacists in addition to willingness to integrating pharmacists in patient care process. Results: Key findings show that all interviewees agree that community pharmacists are important healthcare professionals. However, 7 physicians restrict the role of pharmacists to dispensing medicines. Physicians in Dubai are willing to collaborate with pharmacists, but more than half of them (7) think that pharmacists might interfere with their jobs. Conclusion: The study concludes that all informants agree that collaboration between community pharmacists and physicians definitely enhances patients’ drug therapy outcomes. PMID:27785161

Principles of Research Tissue Banking and Specimen Evaluation from the Pathologist's Perspective.

PubMed

McDonald, Sandra A

2010-12-01

Human tissue biorepositories have an increasingly visible and important role within industrial enterprises in supporting biomedical research, including the rapidly advancing fields of proteomics, pharmacogenomics, and molecular epidemiology. Pathologists play a vital but often underrecognized role in the operation of these tissue banks. Besides interpreting studies that arise from banked samples, pathologists are needed to characterize tissues for research, to conduct quality assurance programs, to assist with resource allocation decisions, and to serve an educational role for investigators using the tissues. This article describes these key principles and illustrates examples where pathologist involvement is crucial to biorepository management. Of overarching importance, pathologists play a critical role in helping biorepository users understand the principles of specimen evaluation (histologic and structural composition of tissues, and their limitations) so as to optimize the scientific benefit of the tissues. In conclusion, greater involvement of pathologists in research tissue banking will enhance the scientific utility of biorepositories.

Can I help you? A qualitative study of pharmacist and pharmacy assistant views on the role of pharmacy assistants in New Zealand.

PubMed

Sheridan, Janie; Kelly, Fiona; Basheer, Mariam; Jan, Reem; Lee, Alice

2011-08-01

To begin to explore the role of PAs more fully in a New Zealand context, through semi-structured interviews with PAs and pharmacists. Semi-structured, qualitative interviews with a convenience sample of pairs of PAs and pharmacists working in a pharmacy together. Pharmacists and PAs both described important roles for PAs. The PAs tended to see themselves as the first point of contact for customers, and that they fulfilled an important healthcare role for the public. Pharmacists agreed that they were the first point of contact yet viewed this more as a gatekeeper role to the pharmacist. Views were also expressed about the difference between PAs and other retail employees. Pharmacists and PAs noted that the 'public' expected PAs to have a basic knowledge of non-prescription medicines and their uses. PAs described difficulties when requesting personal information from customers or asking essential questions where the customer had made a specific product request. Being able to know when to refer to the pharmacist was seen as a key role. Despite being able to describe a number of roles for PAs, these were highly variable. The lack of mandatory training and a clearly articulated role for PAs in New Zealand meant that in some cases PAs might be seen as little more than general retail assistants--a view not in line with their actual roles and practices. Attention to these issues may well help to resolve this, as will public education about the PA's role. © 2011 The Authors. IJPP © 2011 Royal Pharmaceutical Society.

Supporting nurse practitioners' practice in primary healthcare settings: a three-level qualitative model.

PubMed

Chouinard, Véronique; Contandriopoulos, Damien; Perroux, Mélanie; Larouche, Catherine

2017-06-26

While greater reliance on nurse practitioners in primary healthcare settings can improve service efficiency and accessibility, their integration is not straightforward, challenging existing role definitions of both registered nurses and physicians. Developing adequate support practices is therefore essential in primary healthcare nurse practitioners' integration. This study's main objective is to examine different structures and mechanisms put in place to support the development of primary healthcare nurse practitioner's practice in different healthcare settings, and develop a practical model for identifying and planning adequate support practices. This study is part of a larger multicentre study on primary healthcare nurse practitioners in the province of Quebec, Canada. It focuses on three healthcare settings into which one or more primary healthcare nurse practitioners have been integrated. Case studies have been selected to cover a maximum of variations in terms of location, organizational setting, and stages of primary healthcare nurse practitioner integration. Findings are based on the analysis of available documentation in each primary healthcare setting and on semi-structured interviews with key actors in each clinical team. Data were analyzed following thematic and cross-sectional analysis approaches. This article identifies three types of support practices: clinical, team, and systemic. This three-level analysis demonstrates that, on the ground, primary healthcare nurse practitioner integration is essentially a team-based, multilevel endeavour. Despite the existence of a provincial implementation plan, the three settings adopted very different implementation structures and practices, and different actors were involved at each of the three levels. The results also indicated that nursing departments played a decisive role at all three levels. Based on these findings, we suggest that support practices should be adapted to each organization's environment and experience and be modified as needed throughout the integration process. We also stress the importance of combining this approach with a strong coordination mechanism involving managers who have in-depth understanding of nursing professional roles and scopes of practice. Making primary healthcare nurse practitioner integration frameworks more flexible and clarifying and strengthening the role of senior nursing managers could be the key to successful integration.

Topological constraints are major determinants of tRNA tertiary structure and dynamics and provide basis for tertiary folding cooperativity

PubMed Central

Mustoe, Anthony M.; Brooks, Charles L.; Al-Hashimi, Hashim M.

2014-01-01

Recent studies have shown that basic steric and connectivity constraints encoded at the secondary structure level are key determinants of 3D structure and dynamics in simple two-way RNA junctions. However, the role of these topological constraints in higher order RNA junctions remains poorly understood. Here, we use a specialized coarse-grained molecular dynamics model to directly probe the thermodynamic contributions of topological constraints in defining the 3D architecture and dynamics of transfer RNA (tRNA). Topological constraints alone restrict tRNA's allowed conformational space by over an order of magnitude and strongly discriminate against formation of non-native tertiary contacts, providing a sequence independent source of folding specificity. Topological constraints also give rise to long-range correlations between the relative orientation of tRNA's helices, which in turn provides a mechanism for encoding thermodynamic cooperativity between distinct tertiary interactions. These aspects of topological constraints make it such that only several tertiary interactions are needed to confine tRNA to its native global structure and specify functionally important 3D dynamics. We further show that topological constraints are conserved across tRNA's different naturally occurring secondary structures. Taken together, our results emphasize the central role of secondary-structure-encoded topological constraints in defining RNA 3D structure, dynamics and folding. PMID:25217593

Review of concrete biodeterioration in relation to nuclear waste.

PubMed

Turick, Charles E; Berry, Christopher J

2016-01-01

Storage of radioactive waste in concrete structures is a means of containing wastes and related radionuclides generated from nuclear operations in many countries. Previous efforts related to microbial impacts on concrete structures that are used to contain radioactive waste showed that microbial activity can play a significant role in the process of concrete degradation and ultimately structural deterioration. This literature review examines the research in this field and is focused on specific parameters that are applicable to modeling and prediction of the fate of concrete structures used to store or dispose of radioactive waste. Rates of concrete biodegradation vary with the environmental conditions, illustrating a need to understand the bioavailability of key compounds involved in microbial activity. Specific parameters require pH and osmotic pressure to be within a certain range to allow for microbial growth as well as the availability and abundance of energy sources such as components involved in sulfur, iron and nitrogen oxidation. Carbon flow and availability are also factors to consider in predicting concrete biodegradation. The microbial contribution to degradation of the concrete structures containing radioactive waste is a constant possibility. The rate and degree of concrete biodegradation is dependent on numerous physical, chemical and biological parameters. Parameters to focus on for modeling activities and possible options for mitigation that would minimize concrete biodegradation are discussed and include key conditions that drive microbial activity on concrete surfaces. Copyright © 2015. Published by Elsevier Ltd.

The Baby Care Questionnaire: A measure of parenting principles and practices during infancy☆

PubMed Central

Winstanley, Alice; Gattis, Merideth

2013-01-01

The current report provides a new framework to explore the role of parenting practices and principles during infancy. We identify structure and attunement as key parenting principles during infancy. Structure represents reliance on regularity and routines in daily life. Attunement represents reliance on infant cues and close physical contact. We suggest parents’ relative endorsement of these parenting principles is related to their choices about practices such as feeding, holding and night-time sleeping. We designed the Baby Care Questionnaire to measure parents’ endorsement of structure and attunement, as well as their daily parenting practices. We report data demonstrating the factor structure, reliability and validity of the BCQ. The BCQ, to our knowledge, is the first comprehensive measure of parenting practices and principles during infancy. We conclude with a discussion of future directions for the measure. PMID:24050932

Structural determinants in the bulk heterojunction.

PubMed

Acocella, Angela; Höfinger, Siegfried; Haunschmid, Ernst; Pop, Sergiu C; Narumi, Tetsu; Yasuoka, Kenji; Yasui, Masato; Zerbetto, Francesco

2018-02-21

Photovoltaics is one of the key areas in renewable energy research with remarkable progress made every year. Here we consider the case of a photoactive material and study its structural composition and the resulting consequences for the fundamental processes driving solar energy conversion. A multiscale approach is used to characterize essential molecular properties of the light-absorbing layer. A selection of bulk-representative pairs of donor/acceptor molecules is extracted from the molecular dynamics simulation of the bulk heterojunction and analyzed at increasing levels of detail. Significantly increased ground state energies together with an array of additional structural characteristics are identified that all point towards an auxiliary role of the material's structural organization in mediating charge-transfer and -separation. Mechanistic studies of the type presented here can provide important insights into fundamental principles governing solar energy conversion in next-generation photovoltaic devices.

Role of spin-orbit coupling in the electronic structure of Ir O2

NASA Astrophysics Data System (ADS)

Das, Pranab Kumar; Sławińska, Jagoda; Vobornik, Ivana; Fujii, Jun; Regoutz, Anna; Kahk, Juhan M.; Scanlon, David O.; Morgan, Benjamin J.; McGuinness, Cormac; Plekhanov, Evgeny; Di Sante, Domenico; Huang, Ying-Sheng; Chen, Ruei-San; Rossi, Giorgio; Picozzi, Silvia; Branford, William R.; Panaccione, Giancarlo; Payne, David J.

2018-06-01

The delicate interplay of electronic charge, spin, and orbital degrees of freedom is in the heart of many novel phenomena across the transition metal oxide family. Here, by combining high-resolution angle-resolved photoemission spectroscopy and first principles calculations (with and without spin-orbit coupling), the electronic structure of the rutile binary iridate, Ir O2 , is investigated. The detailed study of electronic bands measured on a high-quality single crystalline sample and use of a wide range of photon energy provide a huge improvement over the previous studies. The excellent agreement between theory and experimental results shows that the single-particle DFT description of Ir O2 band structure is adequate, without the need of invoking any treatment of correlation effects. Although many observed features point to a 3D nature of the electronic structure, clear surface effects are revealed. The discussion of the orbital character of the relevant bands crossing the Fermi level sheds light on spin-orbit-coupling-driven phenomena in this material, unveiling a spin-orbit-induced avoided crossing, a property likely to play a key role in its large spin Hall effect.

The characterisation of atomic structure and glass-forming ability of the Zr-Cu-Co metallic glasses studied by molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Celtek, M.; Sengul, S.

2018-03-01

In the present work, the glass formation process and structural properties of Zr50Cu50-xCox (0 ≤ x ≤ 50) bulk metallic glasses were investigated by a molecular dynamics simulation with the many body tight-binding potentials. The evolution of structure and glass formation process with temperature were discussed using the coordination number, the radial distribution functions, the volume-temperature curve, icosahedral short-range order, glass transition temperature, Voronoi analysis, Honeycutt-Andersen pair analysis technique and the distribution of bond-angles. Results indicate that adding Co causes similar responses on the nature of the Zr50Cu50-xCox (0 ≤ x ≤ 50) alloys except for higher glass transition temperature and ideal icosahedral type ordered local atomic environment. Also, the differences of the atomic radii play the key role in influencing the atomic structure of these alloys. Both Cu and Co atoms play a significant role in deciding the chemical and topological short-range orders of the Zr50Cu50-xCox ternary liquids and amorphous alloys. The glass-forming ability of these alloys is supported by the experimental observations reported in the literature up to now.

Common electronic origin of superconductivity in (Li,Fe)OHFeSe bulk superconductor and single-layer FeSe/SrTiO3 films

PubMed Central

Zhao, Lin; Liang, Aiji; Yuan, Dongna; Hu, Yong; Liu, Defa; Huang, Jianwei; He, Shaolong; Shen, Bing; Xu, Yu; Liu, Xu; Yu, Li; Liu, Guodong; Zhou, Huaxue; Huang, Yulong; Dong, Xiaoli; Zhou, Fang; Liu, Kai; Lu, Zhongyi; Zhao, Zhongxian; Chen, Chuangtian; Xu, Zuyan; Zhou, X. J.

2016-01-01

The mechanism of high-temperature superconductivity in the iron-based superconductors remains an outstanding issue in condensed matter physics. The electronic structure plays an essential role in dictating superconductivity. Recent revelation of distinct electronic structure and high-temperature superconductivity in the single-layer FeSe/SrTiO3 films provides key information on the role of Fermi surface topology and interface in inducing or enhancing superconductivity. Here we report high-resolution angle-resolved photoemission measurements on the electronic structure and superconducting gap of an FeSe-based superconductor, (Li0.84Fe0.16)OHFe0.98Se, with a Tc at 41 K. We find that this single-phase bulk superconductor shows remarkably similar electronic behaviours to that of the superconducting single-layer FeSe/SrTiO3 films in terms of Fermi surface topology, band structure and the gap symmetry. These observations provide new insights in understanding high-temperature superconductivity in the single-layer FeSe/SrTiO3 films and the mechanism of superconductivity in the bulk iron-based superconductors. PMID:26853801

Mapping the coupled role of structure and materials in mechanics of platelet-matrix composites

NASA Astrophysics Data System (ADS)

Farzanian, Shafee; Shahsavari, Rouzbeh

2018-03-01

Despite significant progresses on understanding and mimicking the delicate nano/microstructure of biomaterials such as nacre, decoding the indistinguishable merger of materials and structures in controlling the tradeoff in mechanical properties has been long an engineering pursuit. Herein, we focus on an archetype platelet-matrix composite and perform ∼400 nonlinear finite element simulations to decode the complex interplay between various structural features and material characteristics in conferring the balance of mechanical properties. We study various combinatorial models expressed by four key dimensionless parameters, i.e. characteristic platelet length, matrix plasticity, platelet dissimilarity, and overlap offset, whose effects are all condensed in a new unifying parameter, defined as the multiplication of strength, toughness, and stiffness over composite volume. This parameter, which maximizes at a critical characteristic length, controls the transition from intrinsic toughening (matrix plasticity driven without crack growths) to extrinsic toughening phenomena involving progressive crack propagations. This finding, combined with various abstract volumetric and radar plots, will not only shed light on decoupling the complex role of structure and materials on mechanical performance and their trends, but provides important guidelines for designing lightweight staggered platelet-matrix composites while ensuring the best (balance) of their mechanical properties.

Critical Role of Monoclinic Polarization Rotation in High-Performance Perovskite Piezoelectric Materials.

PubMed

Liu, Hui; Chen, Jun; Fan, Longlong; Ren, Yang; Pan, Zhao; Lalitha, K V; Rödel, Jürgen; Xing, Xianran

2017-07-07

High-performance piezoelectric materials constantly attract interest for both technological applications and fundamental research. The understanding of the origin of the high-performance piezoelectric property remains a challenge mainly due to the lack of direct experimental evidence. We perform in situ high-energy x-ray diffraction combined with 2D geometry scattering technology to reveal the underlying mechanism for the perovskite-type lead-based high-performance piezoelectric materials. The direct structural evidence reveals that the electric-field-driven continuous polarization rotation within the monoclinic plane plays a critical role to achieve the giant piezoelectric response. An intrinsic relationship between the crystal structure and piezoelectric performance in perovskite ferroelectrics has been established: A strong tendency of electric-field-driven polarization rotation generates peak piezoelectric performance and vice versa. Furthermore, the monoclinic M_{A} structure is the key feature to superior piezoelectric properties as compared to other structures such as monoclinic M_{B}, rhombohedral, and tetragonal. A high piezoelectric response originates from intrinsic lattice strain, but little from extrinsic domain switching. The present results will facilitate designing high-performance perovskite piezoelectric materials by enhancing the intrinsic lattice contribution with easy and continuous polarization rotation.

Evolution of crystallins for a role in the vertebrate eye lens.

PubMed

Slingsby, Christine; Wistow, Graeme J; Clark, Alice R

2013-04-01

The camera eye lens of vertebrates is a classic example of the re-engineering of existing protein components to fashion a new device. The bulk of the lens is formed from proteins belonging to two superfamilies, the α-crystallins and the βγ-crystallins. Tracing their ancestry may throw light on the origin of the optics of the lens. The α-crystallins belong to the ubiquitous small heat shock proteins family that plays a protective role in cellular homeostasis. They form enormous polydisperse oligomers that challenge modern biophysical methods to uncover the molecular basis of their assembly structure and chaperone-like protein binding function. It is argued that a molecular phenotype of a dynamic assembly suits a chaperone function as well as a structural role in the eye lens where the constraint of preventing protein condensation is paramount. The main cellular partners of α-crystallins, the β- and γ-crystallins, have largely been lost from the animal kingdom but the superfamily is hugely expanded in the vertebrate eye lens. Their structures show how a simple Greek key motif can evolve rapidly to form a complex array of monomers and oligomers. Apart from remaining transparent, a major role of the partnership of α-crystallins with β- and γ-crystallins in the lens is to form a refractive index gradient. Here, we show some of the structural and genetic features of these two protein superfamilies that enable the rapid creation of different assembly states, to match the rapidly changing optical needs among the various vertebrates. Copyright © 2013 The Protein Society.

Evolution of crystallins for a role in the vertebrate eye lens

PubMed Central

Slingsby, Christine; Wistow, Graeme J; Clark, Alice R

2013-01-01

The camera eye lens of vertebrates is a classic example of the re-engineering of existing protein components to fashion a new device. The bulk of the lens is formed from proteins belonging to two superfamilies, the α-crystallins and the βγ-crystallins. Tracing their ancestry may throw light on the origin of the optics of the lens. The α-crystallins belong to the ubiquitous small heat shock proteins family that plays a protective role in cellular homeostasis. They form enormous polydisperse oligomers that challenge modern biophysical methods to uncover the molecular basis of their assembly structure and chaperone-like protein binding function. It is argued that a molecular phenotype of a dynamic assembly suits a chaperone function as well as a structural role in the eye lens where the constraint of preventing protein condensation is paramount. The main cellular partners of α-crystallins, the β- and γ-crystallins, have largely been lost from the animal kingdom but the superfamily is hugely expanded in the vertebrate eye lens. Their structures show how a simple Greek key motif can evolve rapidly to form a complex array of monomers and oligomers. Apart from remaining transparent, a major role of the partnership of α-crystallins with β- and γ-crystallins in the lens is to form a refractive index gradient. Here, we show some of the structural and genetic features of these two protein superfamilies that enable the rapid creation of different assembly states, to match the rapidly changing optical needs among the various vertebrates. PMID:23389822

Structural Basis of the Heterodimer Formation between Cell Shape-Determining Proteins Csd1 and Csd2 from Helicobacter pylori.

PubMed

An, Doo Ri; Im, Ha Na; Jang, Jun Young; Kim, Hyoun Sook; Kim, Jieun; Yoon, Hye Jin; Hesek, Dusan; Lee, Mijoon; Mobashery, Shahriar; Kim, Soon-Jong; Suh, Se Won

2016-01-01

Colonization of the human gastric mucosa by Helicobacter pylori requires its high motility, which depends on the helical cell shape. In H. pylori, several genes (csd1, csd2, csd3/hdpA, ccmA, csd4, csd5, and csd6) play key roles in determining the cell shape by alteration of cross-linking or by trimming of peptidoglycan stem peptides. H. pylori Csd1, Csd2, and Csd3/HdpA are M23B metallopeptidase family members and may act as d,d-endopeptidases to cleave the d-Ala4-mDAP3 peptide bond of cross-linked dimer muropeptides. Csd3 functions also as the d,d-carboxypeptidase to cleave the d-Ala4-d-Ala5 bond of the muramyl pentapeptide. To provide a basis for understanding molecular functions of Csd1 and Csd2, we have carried out their structural characterizations. We have discovered that (i) Csd2 exists in monomer-dimer equilibrium and (ii) Csd1 and Csd2 form a heterodimer. We have determined crystal structures of the Csd2121-308 homodimer and the heterodimer between Csd1125-312 and Csd2121-308. Overall structures of Csd1125-312 and Csd2121-308 monomers are similar to each other, consisting of a helical domain and a LytM domain. The helical domains of both Csd1 and Csd2 play a key role in the formation of homodimers or heterodimers. The Csd1 LytM domain contains a catalytic site with a Zn2+ ion, which is coordinated by three conserved ligands and two water molecules, whereas the Csd2 LytM domain has incomplete metal ligands and no metal ion is bound. Structural knowledge of these proteins sheds light on the events that regulate the cell wall in H. pylori.

Structural Basis of the Heterodimer Formation between Cell Shape-Determining Proteins Csd1 and Csd2 from Helicobacter pylori

PubMed Central

An, Doo Ri; Im, Ha Na; Jang, Jun Young; Kim, Hyoun Sook; Kim, Jieun; Yoon, Hye Jin; Hesek, Dusan; Lee, Mijoon; Mobashery, Shahriar; Kim, Soon-Jong

2016-01-01

Colonization of the human gastric mucosa by Helicobacter pylori requires its high motility, which depends on the helical cell shape. In H. pylori, several genes (csd1, csd2, csd3/hdpA, ccmA, csd4, csd5, and csd6) play key roles in determining the cell shape by alteration of cross-linking or by trimming of peptidoglycan stem peptides. H. pylori Csd1, Csd2, and Csd3/HdpA are M23B metallopeptidase family members and may act as d,d-endopeptidases to cleave the d-Ala4-mDAP3 peptide bond of cross-linked dimer muropeptides. Csd3 functions also as the d,d-carboxypeptidase to cleave the d-Ala4-d-Ala5 bond of the muramyl pentapeptide. To provide a basis for understanding molecular functions of Csd1 and Csd2, we have carried out their structural characterizations. We have discovered that (i) Csd2 exists in monomer-dimer equilibrium and (ii) Csd1 and Csd2 form a heterodimer. We have determined crystal structures of the Csd2121–308 homodimer and the heterodimer between Csd1125–312 and Csd2121–308. Overall structures of Csd1125–312 and Csd2121–308 monomers are similar to each other, consisting of a helical domain and a LytM domain. The helical domains of both Csd1 and Csd2 play a key role in the formation of homodimers or heterodimers. The Csd1 LytM domain contains a catalytic site with a Zn2+ ion, which is coordinated by three conserved ligands and two water molecules, whereas the Csd2 LytM domain has incomplete metal ligands and no metal ion is bound. Structural knowledge of these proteins sheds light on the events that regulate the cell wall in H. pylori. PMID:27711177

The crystal structure of Haloferax volcanii proliferating cell nuclear antigen reveals unique surface charge characteristics due to halophilic adaptation

PubMed Central

Winter, Jody A; Christofi, Panayiotis; Morroll, Shaun; Bunting, Karen A

2009-01-01

Background The high intracellular salt concentration required to maintain a halophilic lifestyle poses challenges to haloarchaeal proteins that must stay soluble, stable and functional in this extreme environment. Proliferating cell nuclear antigen (PCNA) is a fundamental protein involved in maintaining genome integrity, with roles in both DNA replication and repair. To investigate the halophilic adaptation of such a key protein we have crystallised and solved the structure of Haloferax volcanii PCNA (HvPCNA) to a resolution of 2.0 Å. Results The overall architecture of HvPCNA is very similar to other known PCNAs, which are highly structurally conserved. Three commonly observed adaptations in halophilic proteins are higher surface acidity, bound ions and increased numbers of intermolecular ion pairs (in oligomeric proteins). HvPCNA possesses the former two adaptations but not the latter, despite functioning as a homotrimer. Strikingly, the positive surface charge considered key to PCNA's role as a sliding clamp is dramatically reduced in the halophilic protein. Instead, bound cations within the solvation shell of HvPCNA may permit sliding along negatively charged DNA by reducing electrostatic repulsion effects. Conclusion The extent to which individual proteins adapt to halophilic conditions varies, presumably due to their diverse characteristics and roles within the cell. The number of ion pairs observed in the HvPCNA monomer-monomer interface was unexpectedly low. This may reflect the fact that the trimer is intrinsically stable over a wide range of salt concentrations and therefore additional modifications for trimer maintenance in high salt conditions are not required. Halophilic proteins frequently bind anions and cations and in HvPCNA cation binding may compensate for the remarkable reduction in positive charge in the pore region, to facilitate functional interactions with DNA. In this way, HvPCNA may harness its environment as opposed to simply surviving in extreme halophilic conditions. PMID:19698123

Site-specific genetic recombination: hops, flips, and flops.

PubMed

Sadowski, P D

1993-06-01

Genetic recombination plays a key role in the life of organisms as diverse as bacteriophages and humans. Contrary to our idea that chromosomes are stable structures, studies of recombination over the past few decades have shown that in fact DNA replicons are remarkably plastic, undergoing frequent recombination-induced rearrangements. This review summarizes our recent knowledge of the biochemistry of the two major classes of site-specific recombination: 1) transpositional recombination, and 2) conservative site-specific recombination.

Shape of the growing front of biofilms

NASA Astrophysics Data System (ADS)

Wang, Xin; Stone, Howard A.; Golestanian, Ramin

2017-12-01

The spatial organization of bacteria in dense biofilms is key to their collective behaviour, and understanding it will be important for medical and technological applications. Here we study the morphology of a compact biofilm that undergoes unidirectional growth, and determine the condition for the stability of the growing interface as a function of the nutrient concentration and mechanical tension. Our study suggests that transient behaviour may play an important role in shaping the structure of a biofilm.

Mechanism of conformational coupling in SecA: Key role of hydrogen-bonding networks and water interactions.

PubMed

Milenkovic, Stefan; Bondar, Ana-Nicoleta

2016-02-01

SecA uses the energy yielded by the binding and hydrolysis of adenosine triphosphate (ATP) to push secretory pre-proteins across the plasma membrane in bacteria. Hydrolysis of ATP occurs at the nucleotide-binding site, which contains the conserved carboxylate groups of the DEAD-box helicases. Although crystal structures provide valuable snapshots of SecA along its reaction cycle, the mechanism that ensures conformational coupling between the nucleotide-binding site and the other domains of SecA remains unclear. The observation that SecA contains numerous hydrogen-bonding groups raises important questions about the role of hydrogen-bonding networks and hydrogen-bond dynamics in long-distance conformational couplings. To address these questions, we explored the molecular dynamics of SecA from three different organisms, with and without bound nucleotide, in water. By computing two-dimensional hydrogen-bonding maps we identify networks of hydrogen bonds that connect the nucleotide-binding site to remote regions of the protein, and sites in the protein that respond to specific perturbations. We find that the nucleotide-binding site of ADP-bound SecA has a preferred geometry whereby the first two carboxylates of the DEAD motif bridge via hydrogen-bonding water. Simulations of a mutant with perturbed ATP hydrolysis highlight the water-bridged geometry as a key structural element of the reaction path. Copyright © 2015. Published by Elsevier B.V.

The role of conformational selection in the molecular recognition of the wild type and mutants XPA67-80 peptides by ERCC1.

PubMed

Fadda, Elisa

2015-07-01

Molecular recognition is a fundamental step in the coordination of biomolecular pathways. Understanding how recognition and binding occur between highly flexible protein domains is a complex task. The conformational selection theory provides an elegant rationalization of the recognition mechanism, especially valid in cases when unstructured protein regions are involved. The recognition of a poorly structured peptide, namely XPA67-80 , by its target receptor ERCC1, falls in this challenging study category. The microsecond molecular dynamics (MD) simulations, discussed in this work, show that the conformational propensity of the wild type XPA67-80 peptide in solution supports conformational selection as the key mechanism driving its molecular recognition by ERCC1. Moreover, all the mutations of the XPA67-80 peptide studied here cause a significant increase of its conformational disorder, relative to the wild type. Comparison to experimental data suggests that the loss of the recognized structural motifs at the microscopic time scale can contribute to the critical decrease in binding observed for one of the mutants, further substantiating the key role of conformational selection in recognition. Ultimately, because of the high sequence identity and analogy in binding, it is conceivable that the conclusions of this study on the XPA67-80 peptide also apply to the ERCC1-binding domain of the XPA protein. © 2015 Wiley Periodicals, Inc.

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

Mei, Yang; Glover, Karen; Su, Minfei

BECN1 (Beclin 1), a highly conserved eukaryotic protein, is a key regulator of autophagy, a cellular homeostasis pathway, and also participates in vacuolar protein sorting, endocytic trafficking, and apoptosis. BECN1 is important for embryonic development, the innate immune response, tumor suppression, and protection against neurodegenerative disorders, diabetes, and heart disease. BECN1 mediates autophagy as a core component of the class III phosphatidylinositol 3-kinase complexes. However, the exact mechanism by which it regulates the activity of these complexes, or mediates its other diverse functions is unclear. BECN1 interacts with several diverse protein partners, perhaps serving as a scaffold or interaction hubmore » for autophagy. Based on extensive structural, biophysical and bioinformatics analyses, BECN1 consists of an intrinsically disordered region (IDR), which includes a BH3 homology domain (BH3D); a flexible helical domain (FHD); a coiled-coil domain (CCD); and a β-α-repeated autophagy-specific domain (BARAD). Each of these BECN1 domains mediates multiple diverse interactions that involve concomitant conformational changes. Thus, BECN1 conformational flexibility likely plays a key role in facilitating diverse protein interactions. Further, BECN1 conformation and interactions are also modulated by numerous post-translational modifications. A better structure-based understanding of the interplay between different BECN1 conformational and binding states, and the impact of post-translational modifications will be essential to elucidating the mechanism of its multiple biological roles.« less

Critical Contribution of Tyr15 in the HIV-1 Integrase (IN) in Facilitating IN Assembly and Nonenzymatic Function through the IN Precursor Form with Reverse Transcriptase.

PubMed

Takahata, Tatsuro; Takeda, Eri; Tobiume, Minoru; Tokunaga, Kenzo; Yokoyama, Masaru; Huang, Yu-Lun; Hasegawa, Atsuhiko; Shioda, Tatsuo; Sato, Hironori; Kannagi, Mari; Masuda, Takao

2017-01-01

Nonenzymatic roles for HIV-1 integrase (IN) at steps prior to the enzymatic integration step have been reported. To obtain structural and functional insights into the nonenzymatic roles of IN, we performed genetic analyses of HIV-1 IN, focusing on a highly conserved Tyr15 in the N-terminal domain (NTD), which has previously been shown to regulate an equilibrium state between two NTD dimer conformations. Replacement of Tyr15 with alanine, histidine, or tryptophan prevented HIV-1 infection and caused severe impairment of reverse transcription without apparent defects in reverse transcriptase (RT) or in capsid disassembly kinetics after entry into cells. Cross-link analyses of recombinant IN proteins demonstrated that lethal mutations of Tyr15 severely impaired IN structure for assembly. Notably, replacement of Tyr15 with phenylalanine was tolerated for all IN functions, demonstrating that a benzene ring of the aromatic side chain is a key moiety for IN assembly and functions. Additional mutagenic analyses based on previously proposed tetramer models for IN assembly suggested a key role of Tyr15 in facilitating the hydrophobic interaction among IN subunits, together with other proximal residues within the subunit interface. A rescue experiment with a mutated HIV-1 with RT and IN deleted (ΔRT ΔIN) and IN and RT supplied in trans revealed that the nonenzymatic IN function might be exerted through the IN precursor conjugated with RT (RT-IN). Importantly, the lethal mutations of Tyr15 significantly reduced the RT-IN function and assembly. Taken together, Tyr15 seems to play a key role in facilitating the proper assembly of IN and RT on viral RNA through the RT-IN precursor form. Inhibitors of the IN enzymatic strand transfer function (INSTI) have been applied in combination antiretroviral therapies to treat HIV-1-infected patients. Recently, allosteric IN inhibitors (ALLINIs) that interact with HIV-1 IN residues, the locations of which are distinct from the catalytic sites targeted by INSTI, have been discovered. Importantly, ALLINIs affect the nonenzymatic role(s) of HIV-1 IN, providing a rationale for the development of next-generation IN inhibitors with a mechanism that is distinct from that of INSTI. Here, we demonstrate that Tyr15 in the HIV-1 IN NTD plays a critical role during IN assembly by facilitating the hydrophobic interaction of the NTD with the other domains of IN. Importantly, we found that the functional assembly of IN through its fusion form with RT is critical for IN to exert its nonenzymatic function. Our results provide a novel mechanistic insight into the nonenzymatic function of HIV-1 IN and its prevention. Copyright © 2016 American Society for Microbiology.

Rich-Cores in Networks

PubMed Central

Ma, Athen; Mondragón, Raúl J.

2015-01-01

A core comprises of a group of central and densely connected nodes which governs the overall behaviour of a network. It is recognised as one of the key meso-scale structures in complex networks. Profiling this meso-scale structure currently relies on a limited number of methods which are often complex and parameter dependent or require a null model. As a result, scalability issues are likely to arise when dealing with very large networks together with the need for subjective adjustment of parameters. The notion of a rich-club describes nodes which are essentially the hub of a network, as they play a dominating role in structural and functional properties. The definition of a rich-club naturally emphasises high degree nodes and divides a network into two subgroups. Here, we develop a method to characterise a rich-core in networks by theoretically coupling the underlying principle of a rich-club with the escape time of a random walker. The method is fast, scalable to large networks and completely parameter free. In particular, we show that the evolution of the core in World Trade and C. elegans networks correspond to responses to historical events and key stages in their physical development, respectively. PMID:25799585

Rich-cores in networks.

PubMed

Ma, Athen; Mondragón, Raúl J

2015-01-01

A core comprises of a group of central and densely connected nodes which governs the overall behaviour of a network. It is recognised as one of the key meso-scale structures in complex networks. Profiling this meso-scale structure currently relies on a limited number of methods which are often complex and parameter dependent or require a null model. As a result, scalability issues are likely to arise when dealing with very large networks together with the need for subjective adjustment of parameters. The notion of a rich-club describes nodes which are essentially the hub of a network, as they play a dominating role in structural and functional properties. The definition of a rich-club naturally emphasises high degree nodes and divides a network into two subgroups. Here, we develop a method to characterise a rich-core in networks by theoretically coupling the underlying principle of a rich-club with the escape time of a random walker. The method is fast, scalable to large networks and completely parameter free. In particular, we show that the evolution of the core in World Trade and C. elegans networks correspond to responses to historical events and key stages in their physical development, respectively.

The role of emotion in musical improvisation: an analysis of structural features.

PubMed

McPherson, Malinda J; Lopez-Gonzalez, Monica; Rankin, Summer K; Limb, Charles J

2014-01-01

One of the primary functions of music is to convey emotion, yet how music accomplishes this task remains unclear. For example, simple correlations between mode (major vs. minor) and emotion (happy vs. sad) do not adequately explain the enormous range, subtlety or complexity of musically induced emotions. In this study, we examined the structural features of unconstrained musical improvisations generated by jazz pianists in response to emotional cues. We hypothesized that musicians would not utilize any universal rules to convey emotions, but would instead combine heterogeneous musical elements together in order to depict positive and negative emotions. Our findings demonstrate a lack of simple correspondence between emotions and musical features of spontaneous musical improvisation. While improvisations in response to positive emotional cues were more likely to be in major keys, have faster tempos, faster key press velocities and more staccato notes when compared to negative improvisations, there was a wide distribution for each emotion with components that directly violated these primary associations. The finding that musicians often combine disparate features together in order to convey emotion during improvisation suggests that structural diversity may be an essential feature of the ability of music to express a wide range of emotion.

The Role of Emotion in Musical Improvisation: An Analysis of Structural Features

PubMed Central

McPherson, Malinda J.; Lopez-Gonzalez, Monica; Rankin, Summer K.; Limb, Charles J.

2014-01-01

One of the primary functions of music is to convey emotion, yet how music accomplishes this task remains unclear. For example, simple correlations between mode (major vs. minor) and emotion (happy vs. sad) do not adequately explain the enormous range, subtlety or complexity of musically induced emotions. In this study, we examined the structural features of unconstrained musical improvisations generated by jazz pianists in response to emotional cues. We hypothesized that musicians would not utilize any universal rules to convey emotions, but would instead combine heterogeneous musical elements together in order to depict positive and negative emotions. Our findings demonstrate a lack of simple correspondence between emotions and musical features of spontaneous musical improvisation. While improvisations in response to positive emotional cues were more likely to be in major keys, have faster tempos, faster key press velocities and more staccato notes when compared to negative improvisations, there was a wide distribution for each emotion with components that directly violated these primary associations. The finding that musicians often combine disparate features together in order to convey emotion during improvisation suggests that structural diversity may be an essential feature of the ability of music to express a wide range of emotion. PMID:25144200

Structural requirements for PACSIN/Syndapin operation during zebrafish embryonic notochord development.

PubMed

Edeling, Melissa A; Sanker, Subramaniam; Shima, Takaki; Umasankar, P K; Höning, Stefan; Kim, Hye Y; Davidson, Lance A; Watkins, Simon C; Tsang, Michael; Owen, David J; Traub, Linton M

2009-12-03

PACSIN/Syndapin proteins are membrane-active scaffolds that participate in endocytosis. The structure of the Drosophila Syndapin N-terminal EFC domain reveals a crescent shaped antiparallel dimer with a high affinity for phosphoinositides and a unique membrane-inserting prong upon the concave surface. Combined structural, biochemical and reverse genetic approaches in zebrafish define an important role for Syndapin orthologue, Pacsin3, in the early formation of the notochord during embryonic development. In pacsin3-morphant embryos, midline convergence of notochord precursors is defective as axial mesodermal cells fail to polarize, migrate and differentiate properly. The pacsin3 morphant phenotype of a stunted body axis and contorted trunk is rescued by ectopic expression of Drosophila Syndapin, and depends critically on both the prong that protrudes from the surface of the bowed Syndapin EFC domain and the ability of the antiparallel dimer to bind tightly to phosphoinositides. Our data confirm linkage between directional migration, endocytosis and cell specification during embryonic morphogenesis and highlight a key role for Pacsin3 in this coupling in the notochord.

Consequences of cavity size and chemical environment on the adsorption properties of isoreticular metal-organic frameworks: an inverse gas chromatography study.

PubMed

Gutiérrez, Inés; Díaz, Eva; Vega, Aurelio; Ordóñez, Salvador

2013-01-25

The role of the structure of three isoreticular metal-organic frameworks (IRMOFs) on their adsorption behavior has been studied in this work, selecting different kinds of volatile organic compounds (VOCs) as adsorbates (alkanes, alkenes, cycloalkanes, aromatics and chlorinated). For this purpose, three samples (IRMOF-1, IRMOF-8 and IRMOF-10) with cubic structure and without functionalities on the organic linkers were synthesized. Adsorption capacities at infinite dilution were derived from the adsorption isotherms, whereas thermodynamic properties have been determined from chromatographic retention volume. The capacity and the strength of adsorption were strongly influenced by the adsorbate size. This effect is especially relevant for n-alkanes adsorption, indicating the key role of the cavity size on this phenomenon, and hence the importance of the IRMOF structural properties. A different behavior has been observed for the polar compounds, where an enhancement on the specificity of the adsorption with the π-electron rich regions was observed. This fact suggests the specific interaction of these molecules with the organic linkers of the IRMOFs. Copyright © 2012 Elsevier B.V. All rights reserved.

The Impact of Reproductive Technologies on Stallion Mitochondrial Function.

PubMed

Peña, F J; Plaza Davila, M; Ball, B A; Squires, E L; Martin Muñoz, P; Ortega Ferrusola, C; Balao da Silva, C

2015-08-01

The traditional assessment of stallion sperm comprises evaluation of sperm motility and membrane integrity and identification of abnormal morphology of the spermatozoa. More recently, the progressive introduction of flow cytometry is increasing the number of tests available. However, compared with other sperm structures and functions, the evaluation of mitochondria has received less attention in stallion andrology. Recent research indicates that sperm mitochondria are key structures in sperm function suffering major changes during biotechnological procedures such as cryopreservation. In this paper, mitochondrial structure and function will be reviewed in the stallion, when possible specific stallion studies will be discussed, and general findings on mammalian mitochondrial function will be argued when relevant. Especial emphasis will be put on their role as source of reactive oxygen species and in their role regulating sperm lifespan, a possible target to investigate with the aim to improve the quality of frozen-thawed stallion sperm. Later on, the impact of current sperm technologies, principally cryopreservation, on mitochondrial function will be discussed pointing out novel areas of research interest with high potential to improve current sperm technologies. © 2015 Blackwell Verlag GmbH.

Replacing Nitrogen by Sulfur: From Structurally Disordered Eumelanins to Regioregular Thiomelanin Polymers

PubMed Central

Iacomino, Mariagrazia; Mancebo-Aracil, Juan; Guardingo, Mireia; Martín, Raquel; Perfetti, Marco; Manini, Paola; Crescenzi, Orlando; Busqué, Félix; Sedó, Josep; Ruiz-Molina, Daniel

2017-01-01

The oxidative polymerization of 5,6-dihydroxybenzothiophene (DHBT), the sulfur analog of the key eumelanin building block 5,6-dihydroxyindole (DHI), was investigated to probe the role of nitrogen in eumelanin build-up and properties. Unlike DHI, which gives a typical black insoluble eumelanin polymer on oxidation, DHBT is converted to a grayish amorphous solid (referred to as thiomelanin) with visible absorption and electron paramagnetic resonance properties different from those of DHI melanin. Mass spectrometry experiments revealed gradational mixtures of oligomers up to the decamer level. Quite unexpectedly, nuclear magnetic resonance (NMR) analysis of the early oligomer fractions indicated linear, 4-, and 7-linked structures in marked contrast with DHI, which gives highly complex mixtures of partially degraded oligomers. Density functional theory (DFT) calculations supported the tendency of DHBT to couple via the 4- and 7-positions. These results uncover the role of nitrogen as a major determinant of the structural diversity generated by the polymerization of DHI, and point to replacement by sulfur as a viable entry to regioregular eumelanin-type materials for potential applications for surface functionalization by dip coating. PMID:29039817

Crystal structures of the apo and ATP bound Mycobacterium tuberculosis nitrogen regulatory PII protein

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

Shetty, Nishant D.; Reddy, Manchi C.M.; Palaninathan, Satheesh K.

2010-10-11

PII constitutes a family of signal transduction proteins that act as nitrogen sensors in microorganisms and plants. Mycobacterium tuberculosis (Mtb) has a single homologue of PII whose precise role has as yet not been explored. We have solved the crystal structures of the Mtb PII protein in its apo and ATP bound forms to 1.4 and 2.4 {angstrom} resolutions, respectively. The protein forms a trimeric assembly in the crystal lattice and folds similarly to the other PII family proteins. The Mtb PII:ATP binary complex structure reveals three ATP molecules per trimer, each bound between the base of the T-loop ofmore » one subunit and the C-loop of the neighboring subunit. In contrast to the apo structure, at least one subunit of the binary complex structure contains a completely ordered T-loop indicating that ATP binding plays a role in orienting this loop region towards target proteins like the ammonium transporter, AmtB. Arg38 of the T-loop makes direct contact with the {gamma}-phosphate of the ATP molecule replacing the Mg{sup 2+} position seen in the Methanococcus jannaschii GlnK1 structure. The C-loop of a neighboring subunit encloses the other side of the ATP molecule, placing the GlnK specific C-terminal 3{sub 10} helix in the vicinity. Homology modeling studies with the E. coli GlnK:AmtB complex reveal that Mtb PII could form a complex similar to the complex in E. coli. The structural conservation and operon organization suggests that the Mtb PII gene encodes for a GlnK protein and might play a key role in the nitrogen regulatory pathway.« less

Computer-assisted image analysis of human cilia and Chlamydomonas flagella reveals both similarities and differences in axoneme structure.

PubMed

O'Toole, Eileen T; Giddings, Thomas H; Porter, Mary E; Ostrowski, Lawrence E

2012-08-01

In the past decade, investigations from several different fields have revealed the critical role of cilia in human health and disease. Because of the highly conserved nature of the basic axonemal structure, many different model systems have proven useful for the study of ciliopathies, especially the unicellular, biflagellate green alga Chlamydomonas reinhardtii. Although the basic axonemal structure of cilia and flagella is highly conserved, these organelles often perform specialized functions unique to the cell or tissue in which they are found. These differences in function are likely reflected in differences in structural organization. In this work, we directly compare the structure of isolated axonemes from human cilia and Chlamydomonas flagella to identify similarities and differences that potentially play key roles in determining their functionality. Using transmission electron microscopy and 2D image averaging techniques, our analysis has confirmed the overall structural similarity between these two species, but also revealed clear differences in the structure of the outer dynein arms, the central pair projections, and the radial spokes. We also show how the application of 2D image averaging can clarify the underlying structural defects associated with primary ciliary dyskinesia (PCD). Overall, our results document the remarkable similarity between these two structures separated evolutionarily by over a billion years, while highlighting several significant differences, and demonstrate the potential of 2D image averaging to improve the diagnosis and understanding of PCD. Copyright © 2012 Wiley Periodicals, Inc.

Oxytocin and experimental therapeutics in autism spectrum disorders.

PubMed

Bartz, Jennifer A; Hollander, Eric

2008-01-01

Autism is a developmental disorder characterized by three core symptom domains: speech and communication abnormalities, social functioning impairments and repetitive behaviours and restricted interests. Oxytocin (OXT) is a nine-amino-acid peptide that is synthesized in the paraventricular and supraoptic nucleus of the hypothalamus and released into the bloodstream by axon terminals in the posterior pituitary where it plays an important role in facilitating uterine contractions during parturition and in milk let-down. In addition, OXT and the structurally similar peptide arginine vasopressin (AVP) are released within the brain where they play a key role in regulating affiliative behaviours, including sexual behaviour, mother-infant and adult-adult pair-bond formation and social memory/recognition. Finally, OXT has been implicated in repetitive behaviours and stress reactivity. Given that OXT is involved in the regulation of repetitive and affiliative behaviours, and that these are key features of autism, it is believed that OXT may play a role in autism and that OXT may be an effective treatment for these two core symptom domains. In this chapter we review evidence to date supporting a relationship between OXT and autism; we then discuss research looking at the functional role of OXT in autism, as well as a pilot study investigating the therapeutic efficacy of OXT in treating core autism symptom domains. Finally, we conclude with a discussion of directions for future research.

Structure Prediction of the Second Extracellular Loop in G-Protein-Coupled Receptors

PubMed Central

Kmiecik, Sebastian; Jamroz, Michal; Kolinski, Michal

2014-01-01

G-protein-coupled receptors (GPCRs) play key roles in living organisms. Therefore, it is important to determine their functional structures. The second extracellular loop (ECL2) is a functionally important region of GPCRs, which poses significant challenge for computational structure prediction methods. In this work, we evaluated CABS, a well-established protein modeling tool for predicting ECL2 structure in 13 GPCRs. The ECL2s (with between 13 and 34 residues) are predicted in an environment of other extracellular loops being fully flexible and the transmembrane domain fixed in its x-ray conformation. The modeling procedure used theoretical predictions of ECL2 secondary structure and experimental constraints on disulfide bridges. Our approach yielded ensembles of low-energy conformers and the most populated conformers that contained models close to the available x-ray structures. The level of similarity between the predicted models and x-ray structures is comparable to that of other state-of-the-art computational methods. Our results extend other studies by including newly crystallized GPCRs. PMID:24896119

Precambrian Basement Structure Map of the Continental United States - An Interpretation of Geologic and Aeromagnetic Data

USGS Publications Warehouse

Sims, Paul K.; Saltus, Richard W.; Anderson, Eric D.

2008-01-01

The Precambrian basement rocks of the continental United States are largely covered by younger sedimentary and volcanic rocks, and the availability of updated aeromagnetic data (NAMAG, 2002) provides a means to infer major regional basement structures and tie together the scattered, but locally abundant, geologic information. Precambrian basement structures in the continental United States have strongly influenced later Proterozoic and Phanerozoic tectonism within the continent, and there is a growing awareness of the utility of these structures in deciphering major younger tectonic and related episodes. Interest in the role of basement structures in the evolution of continents has been recently stimulated, particularly by publications of the Geological Society of London (Holdsworth and others, 1998; Holdsworth and others, 2001). These publications, as well as others, stress the importance of reactivation of basement structures in guiding the subsequent evolution of continents. Knowledge of basement structures is an important key to understanding the geology of continental interiors.

Minimally Invasive Supraorbital Key-hole Approach for the Treatment of Anterior Cranial Fossa Meningiomas

PubMed Central

IACOANGELI, Maurizio; NOCCHI, Niccolò; NASI, Davide; DI RIENZO, Alessandro; DOBRAN, Mauro; GLADI, Maurizio; COLASANTI, Roberto; ALVARO, Lorenzo; POLONARA, Gabriele; SCERRATI, Massimo

2016-01-01

The most important target of minimally invasive surgery is to obtain the best therapeutic effect with the least iatrogenic injury. In this background, a pivotal role in contemporary neurosurgery is played by the supraorbital key-hole approach proposed by Perneczky for anterior cranial base surgery. In this article, it is presented as a possible valid alternative to the traditional craniotomies in anterior cranial fossa meningiomas removal. From January 2008 to January 2012 at our department 56 patients underwent anterior cranial base meningiomas removal. Thirty-three patients were submitted to traditional approaches while 23 to supraorbital key-hole technique. A clinical and neuroradiological pre- and postoperative evaluation were performed, with attention to eventual complications, length of surgical procedure, and hospitalization. Compared to traditional approaches the supraorbital key-hole approach was associated neither to a greater range of postoperative complications nor to a longer surgical procedure and hospitalization while permitting the same lesion control. With this technique, minimization of brain exposition and manipulation with reduction of unwanted iatrogenic injuries, neurovascular structures preservation, and a better aesthetic result are possible. The supraorbital key-hole approach according to Perneckzy could represent a valid alternative to traditional approaches in anterior cranial base meningiomas surgery. PMID:26804334

Self-Referential Processing, Rumination, and Cortical Midline Structures in Major Depression

PubMed Central

Nejad, Ayna Baladi; Fossati, Philippe; Lemogne, Cédric

2013-01-01

Major depression is associated with a bias toward negative emotional processing and increased self-focus, i.e., the process by which one engages in self-referential processing. The increased self-focus in depression is suggested to be of a persistent, repetitive and self-critical nature, and is conceptualized as ruminative brooding. The role of the medial prefrontal cortex in self-referential processing has been previously emphasized in acute major depression. There is increasing evidence that self-referential processing as well as the cortical midline structures play a major role in the development, course, and treatment response of major depressive disorder. However, the links between self-referential processing, rumination, and the cortical midline structures in depression are still poorly understood. Here, we reviewed brain imaging studies in depressed patients and healthy subjects that have examined these links. Self-referential processing in major depression seems associated with abnormally increased activity of the anterior cortical midline structures. Abnormal interactions between the lateralized task-positive network, and the midline cortical structures of the default mode network, as well as the emotional response network, may underlie the pervasiveness of ruminative brooding. Furthermore, targeting this maladaptive form of rumination and its underlying neural correlates may be key for effective treatment. PMID:24124416

The structures of the SNM1A and SNM1B/Apollo nuclease domains reveal a potential basis for their distinct DNA processing activities

PubMed Central

Allerston, Charles K.; Lee, Sook Y.; Newman, Joseph A.; Schofield, Christopher J.; McHugh, Peter J.; Gileadi, Opher

2015-01-01

The human SNM1A and SNM1B/Apollo proteins are members of an extended family of eukaryotic nuclease containing a motif related to the prokaryotic metallo-β-lactamase (MBL) fold. SNM1A is a key exonuclease during replication-dependent and transcription-coupled interstrand crosslink repair, while SNM1B/Apollo is required for maintaining telomeric overhangs. Here, we report the crystal structures of SNM1A and SNM1B at 2.16 Å. While both proteins contain a typical MBL-β-CASP domain, a region of positive charge surrounds the active site of SNM1A, which is absent in SNM1B and explains the greater apparent processivity of SNM1A. The structures of both proteins also reveal a putative, wide DNA-binding groove. Extensive mutagenesis of this groove, coupled with detailed biochemical analysis, identified residues that did not impact on SNM1A catalytic activity, but drastically reduced its processivity. Moreover, we identified a key role for this groove for efficient digestion past DNA interstrand crosslinks, facilitating the key DNA repair reaction catalysed by SNM1A. Together, the architecture and dimensions of this groove, coupled to the surrounding region of high positive charge, explain the remarkable ability of SNM1A to accommodate and efficiently digest highly distorted DNA substrates, such as those containing DNA lesions. PMID:26582912

Structure of the BTB Domain of Keap1 and Its Interaction with the Triterpenoid Antagonist CDDO

PubMed Central

Cleasby, Anne; Yon, Jeff; Day, Philip J.; Richardson, Caroline; Tickle, Ian J.; Williams, Pamela A.; Callahan, James F.; Carr, Robin; Concha, Nestor; Kerns, Jeffrey K.; Qi, Hongwei; Sweitzer, Thomas; Ward, Paris; Davies, Thomas G.

2014-01-01

The protein Keap1 is central to the regulation of the Nrf2-mediated cytoprotective response, and is increasingly recognized as an important target for therapeutic intervention in a range of diseases involving excessive oxidative stress and inflammation. The BTB domain of Keap1 plays key roles in sensing environmental electrophiles and in mediating interactions with the Cul3/Rbx1 E3 ubiquitin ligase system, and is believed to be the target for several small molecule covalent activators of the Nrf2 pathway. However, despite structural information being available for several BTB domains from related proteins, there have been no reported crystal structures of Keap1 BTB, and this has precluded a detailed understanding of its mechanism of action and interaction with antagonists. We report here the first structure of the BTB domain of Keap1, which is thought to contain the key cysteine residue responsible for interaction with electrophiles, as well as structures of the covalent complex with the antagonist CDDO/bardoxolone, and of the constitutively inactive C151W BTB mutant. In addition to providing the first structural confirmation of antagonist binding to Keap1 BTB, we also present biochemical evidence that adduction of Cys 151 by CDDO is capable of inhibiting the binding of Cul3 to Keap1, and discuss how this class of compound might exert Nrf2 activation through disruption of the BTB-Cul3 interface. PMID:24896564

Role for chondroitin sulfate glycosaminoglycan in NEDD9-mediated breast cancer cell growth.

PubMed

Iida, Joji; Dorchak, Jesse; Clancy, Rebecca; Slavik, Juliana; Ellsworth, Rachel; Katagiri, Yasuhiro; Pugacheva, Elena N; van Kuppevelt, Toin H; Mural, Richard J; Cutler, Mary Lou; Shriver, Craig D

2015-01-15

There are lines of evidence demonstrating that NEDD9 (Cas-L, HEF-1) plays a key role in the development, progression, and metastasis of breast cancer cells. We previously reported that NEDD9 plays a critical role for promoting migration and growth of MDA-MB-231. In order to further characterize the mechanisms of NEDD9-mediated cancer migration and growth, stable cells overexpressing NEDD9 were generated using HCC38 as a parental cell line which expresses low level of endogenous NEDD9. Microarray studies demonstrated that core proteins of CD44 and Serglycin were markedly upregulated in HCC38(NEDD9) cells compared to HCC38(Vector) cells, while those of Syndecan-1, Syndecan-2, and Versican were downregulated in HCC38(NEDD9). Importantly, enzymes generating chondroitin sulfate glycosaminoglycans (CS) such as CHST11, CHST15, and CSGALNACT1 were upregulated in HCC38(NEDD9) compared to HCC38(Vector). Immunofluorescence studies using specific antibody, GD3G7, confirmed the enhanced expression of CS-E subunit in HCC38(NEDD9). Immunoprecipitation and western blotting analysis demonstrated that CS-E was attached to CD44 core protein. We demonstrated that removing CS by chondroitinase ABC significantly inhibited anchorage-independent colony formation of HCC38(NEDD9) in methylcellulose. Importantly, the fact that GD3G7 significantly inhibited colony formation of HCC38(NEDD9) cells suggests that CS-E subunit plays a key role in this process. Furthermore, treatment of HCC38(NEDD9) cells with chondroitinase ABC or GD3G7 significantly inhibited mammosphere formation. Exogenous addition of CS-E enhanced colony formation and mammosphere formation of HCC38 parental and HCC38(Vector) cells. These results suggest that NEDD9 regulates the synthesis and expression of tumor associated glycocalyx structures including CS-E, which plays a key role in promoting and regulating breast cancer progression and metastasis and possibly stem cell phenotypes. Copyright © 2014 Elsevier Inc. All rights reserved.

Peroxisome proliferator-activated receptor α ligands and modulators from dietary compounds: Types, screening methods and functions.

PubMed

Yang, Haixia; Xiao, Lei; Wang, Nanping

2017-04-01

Peroxisome proliferator-activated receptor α (PPARα) plays a key role in lipid metabolism and glucose homeostasis and a crucial role in the prevention and treatment of metabolic diseases. Natural dietary compounds, including nutrients and phytochemicals, are PPARα ligands or modulators. High-throughput screening assays have been developed to screen for PPARα ligands and modulators in our diet. In the present review, we discuss recent advances in our knowledge of PPARα, including its structure, function, and ligand and modulator screening assays, and summarize the different types of dietary PPARα ligands and modulators. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Brillouin gain enhancement in nano-scale photonic waveguide

NASA Astrophysics Data System (ADS)

Nouri Jouybari, Soodabeh

2018-05-01

The enhancement of stimulated Brillouin scattering in nano-scale waveguides has a great contribution in the improvement of the photonic devices technology. The key factors in Brillouin gain are the electrostriction force and radiation pressure generated by optical waves in the waveguide. In this article, we have proposed a new scheme of nano-scale waveguide in which the Brillouin gain is considerably improved compared to the previously-reported schemes. The role of radiation pressure in the Brillouin gain was much higher than the role of the electrostriction force. The Brillouin gain strongly depends on the structural parameters of the waveguide and the maximum value of 12127 W-1 m-1 is obtained for the Brillouin gain.

Serine protease inhibitors of parasitic helminths.

PubMed

Molehin, Adebayo J; Gobert, Geoffrey N; McManus, Donald P

2012-05-01

Serine protease inhibitors (serpins) are a superfamily of structurally conserved proteins that inhibit serine proteases and play key physiological roles in numerous biological systems such as blood coagulation, complement activation and inflammation. A number of serpins have now been identified in parasitic helminths with putative involvement in immune regulation and in parasite survival through interference with the host immune response. This review describes the serpins and smapins (small serine protease inhibitors) that have been identified in Ascaris spp., Brugia malayi, Ancylostoma caninum Onchocerca volvulus, Haemonchus contortus, Trichinella spiralis, Trichostrongylus vitrinus, Anisakis simplex, Trichuris suis, Schistosoma spp., Clonorchis sinensis, Paragonimus westermani and Echinococcus spp. and discusses their possible biological functions, including roles in host-parasite interplay and their evolutionary relationships.

On the role of the SMA in the discrete sequence production task: a TMS study. Transcranial Magnetic Stimulation.

PubMed

Verwey, Willem B; Lammens, Robin; van Honk, Jack

2002-01-01

Participants practiced two discrete six-key sequences for a total of 420 trials. The 1 x 6 sequence had a unique order of key presses while the 2 x 3 sequence involved repetition of a three-key segment. Both sequences showed a long interkey interval halfway the sequence indicating hierarchical sequence control in that not only the 2 x 3 but also the 1 x 6 sequence was executed as two successive motor chunks. Besides, the second part of both sequences was executed faster than the first part. This supports the earlier notion of a motor processor executing the elements of familiar motor chunks and a cognitive processor triggering either these motor chunks or individual sequence elements. Low-frequency, off-line transcranial magnetic stimulation (TMS) of the supplementary motor area (SMA) counteracted normal improvement with practice of key presses at all sequence positions. Together, these results are in line with the notion that with moderate practice, the SMA executes short sequence fragments that are concatenated by other brain structures.

Secure Multicast Tree Structure Generation Method for Directed Diffusion Using A* Algorithms

NASA Astrophysics Data System (ADS)

Kim, Jin Myoung; Lee, Hae Young; Cho, Tae Ho

The application of wireless sensor networks to areas such as combat field surveillance, terrorist tracking, and highway traffic monitoring requires secure communication among the sensor nodes within the networks. Logical key hierarchy (LKH) is a tree based key management model which provides secure group communication. When a sensor node is added or evicted from the communication group, LKH updates the group key in order to ensure the security of the communications. In order to efficiently update the group key in directed diffusion, we propose a method for secure multicast tree structure generation, an extension to LKH that reduces the number of re-keying messages by considering the addition and eviction ratios of the history data. For the generation of the proposed key tree structure the A* algorithm is applied, in which the branching factor at each level can take on different value. The experiment results demonstrate the efficiency of the proposed key tree structure against the existing key tree structures of fixed branching factors.

Soil Organic Matter in Its Native State: Unravelling the Most Complex Biomaterial on Earth.

PubMed

Masoom, Hussain; Courtier-Murias, Denis; Farooq, Hashim; Soong, Ronald; Kelleher, Brian P; Zhang, Chao; Maas, Werner E; Fey, Michael; Kumar, Rajeev; Monette, Martine; Stronks, Henry J; Simpson, Myrna J; Simpson, André J

2016-02-16

Since the isolation of soil organic matter in 1786, tens of thousands of publications have searched for its structure. Nuclear magnetic resonance (NMR) spectroscopy has played a critical role in defining soil organic matter but traditional approaches remove key information such as the distribution of components at the soil-water interface and conformational information. Here a novel form of NMR with capabilities to study all physical phases termed Comprehensive Multiphase NMR, is applied to analyze soil in its natural swollen-state. The key structural components in soil organic matter are identified to be largely composed of macromolecular inputs from degrading biomass. Polar lipid heads and carbohydrates dominate the soil-water interface while lignin and microbes are arranged in a more hydrophobic interior. Lignin domains cannot be penetrated by aqueous solvents even at extreme pH indicating they are the most hydrophobic environment in soil and are ideal for sequestering hydrophobic contaminants. Here, for the first time, a complete range of physical states of a whole soil can be studied. This provides a more detailed understanding of soil organic matter at the molecular level itself key to develop the most efficient soil remediation and agricultural techniques, and better predict carbon sequestration and climate change.

Identifying structural barriers to an effective HIV response: using the National Composite Policy Index data to evaluate the human rights, legal and policy environment

PubMed Central

Gruskin, Sofia; Ferguson, Laura; Alfven, Tobias; Rugg, Deborah; Peersman, Greet

2013-01-01

Introduction Attention to the negative effects of structural barriers on HIV efforts is increasing. Reviewing national legal and policy environments with attention to the international human rights commitments of states is a means of assessing and providing focus for addressing these barriers to effective HIV responses. Methods Law and policy data from the 171 countries reporting under the Declaration of Commitment from the 2001 United Nations General Assembly Special Session on HIV/AIDS were analyzed to assess attention to human rights in national legal and policy environments as relevant to the health and rights of key populations such as people who inject drugs, men who have sex with men and sex workers. Results Seventy-eight governments and civil society in 106 countries report the existence of laws and policies which present obstacles to accessing HIV services for key populations. Laws and policies which positively affect access to HIV-related services, in and of themselves constituting structural interventions, were also reported. The dissonance between laws and how this impacts the availability and use of HIV-related services deserve greater attention. Conclusions Recognition of the harms inherent in laws that constitute structural barriers to effective HIV responses and the potential positive role that a supportive legal environment can play suggests the need for legal reform to ensure an enabling regulatory framework within which HIV services can be effectively delivered and used by the populations who need them. Moving beyond laws and policies, further efforts are required to determine how to capture information on the range of structural barriers. Teasing apart the impact of different barriers, as well as the structural interventions put in place to address them, remains complicated. Capturing the impact of policy and legal interventions can ultimately support governments and civil society to ensure the human rights of key populations are protected in national HIV responses. PMID:23621903

Identifying structural barriers to an effective HIV response: using the National Composite Policy Index data to evaluate the human rights, legal and policy environment.

PubMed

Gruskin, Sofia; Ferguson, Laura; Alfven, Tobias; Rugg, Deborah; Peersman, Greet

2013-04-26

Attention to the negative effects of structural barriers on HIV efforts is increasing. Reviewing national legal and policy environments with attention to the international human rights commitments of states is a means of assessing and providing focus for addressing these barriers to effective HIV responses. Law and policy data from the 171 countries reporting under the Declaration of Commitment from the 2001 United Nations General Assembly Special Session on HIV/AIDS were analyzed to assess attention to human rights in national legal and policy environments as relevant to the health and rights of key populations such as people who inject drugs, men who have sex with men and sex workers. Seventy-eight governments and civil society in 106 countries report the existence of laws and policies which present obstacles to accessing HIV services for key populations. Laws and policies which positively affect access to HIV-related services, in and of themselves constituting structural interventions, were also reported. The dissonance between laws and how this impacts the availability and use of HIV-related services deserve greater attention. Recognition of the harms inherent in laws that constitute structural barriers to effective HIV responses and the potential positive role that a supportive legal environment can play suggests the need for legal reform to ensure an enabling regulatory framework within which HIV services can be effectively delivered and used by the populations who need them. Moving beyond laws and policies, further efforts are required to determine how to capture information on the range of structural barriers. Teasing apart the impact of different barriers, as well as the structural interventions put in place to address them, remains complicated. Capturing the impact of policy and legal interventions can ultimately support governments and civil society to ensure the human rights of key populations are protected in national HIV responses.

Cations Modulate Actin Bundle Mechanics, Assembly Dynamics, and Structure.

PubMed

Castaneda, Nicholas; Zheng, Tianyu; Rivera-Jacquez, Hector J; Lee, Hyun-Ju; Hyun, Jaekyung; Balaeff, Alexander; Huo, Qun; Kang, Hyeran

2018-04-12

Actin bundles are key factors in the mechanical support and dynamic reorganization of the cytoskeleton. High concentrations of multivalent counterions promote bundle formation through electrostatic attraction between actin filaments that are negatively charged polyelectrolytes. In this study, we evaluate how physiologically relevant divalent cations affect the mechanical, dynamic, and structural properties of actin bundles. Using a combination of total internal reflection fluorescence microscopy, transmission electron microscopy, and dynamic light scattering, we demonstrate that divalent cations modulate bundle stiffness, length distribution, and lateral growth. Molecular dynamics simulations of an all-atom model of the actin bundle reveal specific actin residues coordinate cation-binding sites that promote the bundle formation. Our work suggests that specific cation interactions may play a fundamental role in the assembly, structure, and mechanical properties of actin bundles.

Pt-Bi Antibonding Interaction: The Key Factor for Superconductivity in Monoclinic BaPt2Bi2.

PubMed

Gui, Xin; Xing, Lingyi; Wang, Xiaoxiong; Bian, Guang; Jin, Rongying; Xie, Weiwei

2018-02-19

In the search for superconductivity in a BaAu 2 Sb 2 -type monoclinic structure, we have successfully synthesized the new compound BaPt 2 Bi 2 , which crystallizes in the space group P2 1 /m (No. 11; Pearson symbol mP10) according to a combination of powder and single-crystal X-ray diffraction and scanning electron microscopy. A sharp electrical resistivity drop and large diamagnetic magnetization below 2.0 K indicates it owns superconducting ground state. This makes BaPt 2 Bi 2 the first reported superconductor in a monoclinic BaAu 2 Sb 2 -type structure, a previously unappreciated structure for superconductivity. First-principles calculations considering spin-orbit coupling indicate that Pt-Bi antibonding interaction plays a critical role in inducing superconductivity.

Complex structures from patterned cell sheets

PubMed Central

Misra, M.; Audoly, B.; Shvartsman, S. Y.

2017-01-01

The formation of three-dimensional structures from patterned epithelial sheets plays a key role in tissue morphogenesis. An important class of morphogenetic mechanisms relies on the spatio-temporal control of apical cell contractility, which can result in the localized bending of cell sheets and in-plane cell rearrangements. We have recently proposed a modified vertex model that can be used to systematically explore the connection between the two-dimensional patterns of cell properties and the emerging three-dimensional structures. Here we review the proposed modelling framework and illustrate it through the computational analysis of the vertex model that captures the salient features of the formation of the dorsal appendages during Drosophila oogenesis. This article is part of the themed issue ‘Systems morphodynamics: understanding the development of tissue hardware’. PMID:28348251

Hippocampal structure and human cognition: key role of spatial processing and evidence supporting the efficiency hypothesis in females

PubMed Central

Colom, Roberto; Stein, Jason L.; Rajagopalan, Priya; Martínez, Kenia; Hermel, David; Wang, Yalin; Álvarez-Linera, Juan; Burgaleta, Miguel; Quiroga, MªÁngeles; Shih, Pei Chun; Thompson, Paul M.

2014-01-01

Here we apply a method for automated segmentation of the hippocampus in 3D high-resolution structural brain MRI scans. One hundred and four healthy young adults completed twenty one tasks measuring abstract, verbal, and spatial intelligence, along with working memory, executive control, attention, and processing speed. After permutation tests corrected for multiple comparisons across vertices (p < .05) significant relationships were found for spatial intelligence, spatial working memory, and spatial executive control. Interactions with sex revealed significant relationships with the general factor of intelligence (g), along with abstract and spatial intelligence. These correlations were mainly positive for males but negative for females, which might support the efficiency hypothesis in women. Verbal intelligence, attention, and processing speed were not related to hippocampal structural differences. PMID:25632167

LncRNA Structural Characteristics in Epigenetic Regulation

PubMed Central

Wang, Chenguang; Wang, Lianzong; Ding, Yu; Lu, Xiaoyan; Zhang, Guosi; Yang, Jiaxin; Zheng, Hewei; Wang, Hong; Jiang, Yongshuai; Xu, Liangde

2017-01-01

The rapid development of new generation sequencing technology has deepened the understanding of genomes and functional products. RNA-sequencing studies in mammals show that approximately 85% of the DNA sequences have RNA products, for which the length greater than 200 nucleotides (nt) is called long non-coding RNAs (lncRNA). LncRNAs now have been shown to play important epigenetic regulatory roles in key molecular processes, such as gene expression, genetic imprinting, histone modification, chromatin dynamics, and other activities by forming specific structures and interacting with all kinds of molecules. This paper mainly discusses the correlation between the structure and function of lncRNAs with the recent progress in epigenetic regulation, which is important to the understanding of the mechanism of lncRNAs in physiological and pathological processes. PMID:29292750

Role of organic matter on aggregate stability and related mechanisms through organic amendments

NASA Astrophysics Data System (ADS)

Zaher, Hafida

2010-05-01

To date, only a few studies have tried to simultaneously compare the role of neutral and uronic sugars and lipids on soil structural stability. Moreover, evidence for the mechanisms involved has often been established following wetting of moist aggregates after various pre-treatments thus altering aggregate structure and resulting in manipulations on altered aggregates on which the rapid wetting process may not be involved anymore. To the best of our knowledge, the objective of this work was to study the role of neutral and uronic sugars and lipids in affecting key mechanisms (swelling rate, pressure evolution) involved in the stabilization of soil structure. A long-term incubation study (48-wk) was performed on a clay loam and a silty-clay loam amended with de-inking-secondary sludge mix at three rates (8, 16 and 24 Mg dry matter ha-1), primary-secondary sludge mix at one rate (18 Mg oven-dry ha-1) and composted de-inking sludge at one rate (24 Mg ha-1). Different structural stability indices (stability of moist and dry aggregates, the amount of dispersible clay and loss of soil material following sudden wetting) were measured on a regular basis during the incubation, along with CO2 evolved, neutral and uronic sugar, and lipid contents. During the course of the incubations, significant increases in all stability indices were measured for both soil types. In general, the improvements in stability were proportional to the amount of C added as organic amendments. These improvements were linked to a very intense phase of C mineralization and associated with increases in neutral and uronic sugars as well as lipid contents. The statistical relationships found between the different carbonaceous fractions and stability indices were all highly significant and indicated no clear superiority of one fraction over another. Paper sludge amendments also resulted in significant decreases in maximum internal pressure of aggregate and aggregate swelling following immersion in water, two mechanisms affecting structural stability. Overall, the results suggest that reduction in maximum internal pressure induced by organic amendments most likely resulted from increases in pore surface roughness and pore occlusion rather than by increase in surface wetting angles. This study also supports the view of a non specific action of the lipids, neutral and uronic sugars on aggregate stability to rapid wetting. Key words: soil aggregate stability, polysaccharides, lipids, mechanisms, organic matter

Situational and dispositional influences on nurses' workplace well-being: the role of empowering unit leadership.

PubMed

Spence Laschinger, Heather K; Finegan, Joan; Wilk, Piotr

2011-01-01

Unit-level leadership and structural empowerment play key roles in creating healthy work environments, yet few researchers have examined these contextual effects on nurses' well-being. The aim of this study was to test a multilevel model of structural empowerment examining the effect of nursing unit leadership quality and structural empowerment on nurses' experiences of burnout and job satisfaction and to examine the effect of a personal dispositional variable, core self-evaluation, on these nurse experiences. Nurses (n = 3,156) from 217 hospital units returned surveys that included measures of leader-member exchange, structural empowerment, burnout, core self-evaluation, and job satisfaction. Multilevel structural equation modeling was used to test the model. Nurses' shared perceptions of leader-member exchange quality on their units positively influenced their shared perceptions of unit structural empowerment (Level 2), which resulted in significantly higher levels of individual nurse job satisfaction (Level 1). Unit-level leader-member exchange quality also directly influenced individual nurse job satisfaction. Unit leader-member exchange quality and structural empowerment influenced emotional exhaustion and cynicism differentially. Higher unit-level leader-member exchange quality was associated with lower cynicism; higher unit-level structural empowerment was associated with lower emotional exhaustion. At Level 1, higher core self-evaluation was associated with lower levels of both emotional exhaustion and cynicism, both of which were associated with lower job satisfaction. This study provides a theoretical understanding of how unit leadership affects both unit- and individual-level outcomes.

Insights into Brain Glycogen Metabolism

PubMed Central

Mathieu, Cécile; de la Sierra-Gallay, Ines Li; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

2016-01-01

Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. PMID:27402852

Morphology and mechanical properties of multi-stranded amyloid fibrils probed by atomistic and coarse-grained simulations

NASA Astrophysics Data System (ADS)

Yoon, Gwonchan; Lee, Myeongsang; Kim, Kyungwoo; In Kim, Jae; Chang, Hyun Joon; Baek, Inchul; Eom, Kilho; Na, Sungsoo

2015-12-01

Amyloid fibrils are responsible for pathogenesis of various diseases and exhibit the structural feature of an ordered, hierarchical structure such as multi-stranded helical structure. As the multi-strandedness of amyloid fibrils has recently been found to be highly correlated with their toxicity and infectivity, it is necessary to study how the hierarchical (i.e. multi-stranded) structure of amyloid fibril is formed. Moreover, although it has recently been reported that the nanomechanics of amyloid proteins plays a key role on the amyloid-induced pathogenesis, a critical role that the multi-stranded helical structure of the fibrils plays in their nanomechanical properties has not fully characterized. In this work, we characterize the morphology and mechanical properties of multi-stranded amyloid fibrils by using equilibrium molecular dynamics simulation and elastic network model. It is shown that the helical pitch of multi-stranded amyloid fibril is linearly proportional to the number of filaments comprising the amyloid fibril, and that multi-strandedness gives rise to improving the bending rigidity of the fibril. Moreover, we have also studied the morphology and mechanical properties of a single protofilament (filament) in order to understand the effect of cross-β structure and mutation on the structures and mechanical properties of amyloid fibrils. Our study sheds light on the underlying design principles showing how the multi-stranded amyloid fibril is formed and how the structure of amyloid fibrils governs their nanomechanical properties.

Screen-related sedentary behaviours of school-aged children: Principals’ and teachers’ perspectives

PubMed Central

He, Meizi; Piché, Leonard; Beynon, Charlene; Kurtz, Joanne; Harris, Stewart

2010-01-01

Objective To solicit school principals’ and teachers’ perspectives on children’s screen-related sedentary behaviour and to identify possible solutions to reduce sedentary behaviours among school-aged children. Method In-person interviews using a semi-structured interview guide were conducted with school principals and grades five and six classroom teachers in 14 randomly selected elementary schools in London and Middlesex County, Ontario. Fourteen principals and 39 classroom teachers participated in the study. Inductive content analysis was performed independently by two researchers. Results Both principals and teachers were very concerned about children’s excessive screen activities, but they did not perceive that they could play a key role in reducing these behaviours. Key barriers were identified to reducing screen-related sedentary behaviour and to children’s active living both at and away from school. They included competing demands from other subjects, limited gym resources/space within the school, a lack of control over the home environment, and a perception that parents were poor role models. Notwithstanding the above barriers, principals and teachers still recommended increasing children’s daily physical activity both within and outside of school hours. Furthermore, they stressed the need for parents to play a key role in reducing their children’s screen-related sedentary behaviours and increasing their level of physical activity. Conclusion School principals and teachers were very concerned about excessive screen-behaviour among school-aged children when away from school and suggested that interventions should emphasize increasing daily physical education, promoting recreational sports at or away from school, and engaging parents in regulating screen time at home. PMID:21468163

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

Holt, Allison M; Standaert, Robert F; Jubb, Aaron M

Biological membranes, formed primarily by the self-assembly of complex mixtures of phospholipids, provide a structured scaffold for compartmentalization and structural processes in living cells. The specific physical properties of phospholipid species present in a given membrane play a key role in mediating these processes. Phosphatidylethanolamine (PE), a zwitterionic lipid present in bacterial, yeast, and mammalian cell membranes, is exceptional. In addition to undergoing the standard lipid polymorphic transition between the gel and liquid-crystalline phase, it can also assume an unusual polymorphic state, the inverse hexagonal phase (HII). Divalent cations are among the factors that drive the formation of the HIImore » phase, wherein the lipid molecules form stacked tubular structures by burying the hydrophilic head groups and exposing the hydrophobic tails to the bulk solvent. Most biological membranes contain a lipid species capable of forming the HII state suggesting that such lipid polymorphic structural states play an important role in structural biological processes such as membrane fusion. In this study, the interactions between Mg2+ and biomimetic bacterial cell membranes composed of PE and phosphatidylglycerol (PG) were probed using differential scanning calorimetry (DSC), small-angle x-ray scattering (SAXS), and fluorescence spectroscopy. The lipid phase transitions were examined at varying ratios of PE to PG and upon exposure to physiologically relevant concentrations of Mg2+. An understanding of these basic interactions enhances our understanding of membrane dynamics and how membrane-mediated structural changes may occur in vivo.« less

Conserved water molecules in bacterial serine hydroxymethyltransferases.

PubMed

Milano, Teresa; Di Salvo, Martino Luigi; Angelaccio, Sebastiana; Pascarella, Stefano

2015-10-01

Water molecules occurring in the interior of protein structures often are endowed with key structural and functional roles. We report the results of a systematic analysis of conserved water molecules in bacterial serine hydroxymethyltransferases (SHMTs). SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of l-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The approach utilized in this study relies on two programs, ProACT2 and WatCH. The first software is able to categorize water molecules in a protein crystallographic structure as buried, positioned in clefts or at the surface. The other program finds, in a set of superposed homologous proteins, water molecules that occur approximately in equivalent position in each of the considered structures. These groups of molecules are referred to as 'clusters' and represent structurally conserved water molecules. Several conserved clusters of buried or cleft water molecules were found in the set of 11 bacterial SHMTs we took into account for this work. The majority of these clusters were not described previously. Possible structural and functional roles for the conserved water molecules are envisaged. This work provides a map of the conserved water molecules helpful for deciphering SHMT mechanism and for rational design of molecular engineering experiments. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.