Probing protein flexibility reveals a mechanism for selective promiscuity

PubMed Central

Pabon, Nicolas A; Camacho, Carlos J

2017-01-01

Many eukaryotic regulatory proteins adopt distinct bound and unbound conformations, and use this structural flexibility to bind specifically to multiple partners. However, we lack an understanding of how an interface can select some ligands, but not others. Here, we present a molecular dynamics approach to identify and quantitatively evaluate the interactions responsible for this selective promiscuity. We apply this approach to the anticancer target PD-1 and its ligands PD-L1 and PD-L2. We discover that while unbound PD-1 exhibits a hard-to-drug hydrophilic interface, conserved specific triggers encoded in the cognate ligands activate a promiscuous binding pathway that reveals a flexible hydrophobic binding cavity. Specificity is then established by additional contacts that stabilize the PD-1 cavity into distinct bound-like modes. Collectively, our studies provide insight into the structural basis and evolution of multiple binding partners, and also suggest a biophysical approach to exploit innate binding pathways to drug seemingly undruggable targets. DOI: http://dx.doi.org/10.7554/eLife.22889.001 PMID:28432789

Three-dimensional printing-based electro-millifluidic devices for fabricating multi-compartment particles.

PubMed

Chen, Qiu Lan; Liu, Zhou; Shum, Ho Cheung

2014-11-01

In this work, we demonstrate the use of stereolithographic 3D printing to fabricate millifluidic devices, which are used to engineer particles with multiple compartments. As the 3D design is directly transferred to the actual prototype, this method accommodates 3D millimeter-scaled features that are difficult to achieve by either lithographic-based microfabrication or traditional macrofabrication techniques. We exploit this approach to produce millifluidic networks to deliver multiple fluidic components. By taking advantage of the laminar flow, the fluidic components can form liquid jets with distinct patterns, and each pattern has clear boundaries between the liquid phases. Afterwards, droplets with controlled size are fabricated by spraying the liquid jet in an electric field, and subsequently converted to particles after a solidification step. As a demonstration, we fabricate calcium alginate particles with structures of (1) slice-by-slice multiple lamellae, (2) concentric core-shells, and (3) petals surrounding the particle centers. Furthermore, distinct hybrid particles combining two or more of the above structures are also obtained. These compartmentalized particles impart spatially dependent functionalities and properties. To show their applicability, various ingredients, including fruit juices, drugs, and magnetic nanoparticles are encapsulated in the different compartments as proof-of-concepts for applications, including food, drug delivery, and bioassays. Our 3D printed electro-millifluidic approach represents a convenient and robust method to extend the range of structures of functional particles.

Spatial structure favors cooperative behavior in the snowdrift game with multiple interactive dynamics

NASA Astrophysics Data System (ADS)

Su, Qi; Li, Aming; Wang, Long

2017-02-01

Spatial reciprocity is generally regarded as a positive rule facilitating the evolution of cooperation. However, a few recent studies show that, in the snowdrift game, spatial structure still could be detrimental to cooperation. Here we propose a model of multiple interactive dynamics, where each individual can cooperate and defect simultaneously against different neighbors. We realize individuals' multiple interactions simply by endowing them with strategies relevant to probabilities, and every one decides to cooperate or defect with a probability. With multiple interactive dynamics, the cooperation level in square lattices is higher than that in the well-mixed case for a wide range of cost-to-benefit ratio r, implying that spatial structure favors cooperative behavior in the snowdrift game. Moreover, in square lattices, the most favorable strategy follows a simple relation of r, which confers theoretically the average evolutionary frequency of cooperative behavior. We further extend our study to various homogeneous and heterogeneous networks, which demonstrates the robustness of our results. Here multiple interactive dynamics stabilizes the positive role of spatial structure on the evolution of cooperation and individuals' distinct reactions to different neighbors can be a new line in understanding the emergence of cooperation.

Classification of the nonlinear dynamics and bifurcation structure of ultrasound contrast agents excited at higher multiples of their resonance frequency

NASA Astrophysics Data System (ADS)

Sojahrood, Amin Jafari; Kolios, Michael C.

2012-07-01

Through numerical simulation of the Hoff model we show that when ultrasound contrast agents (UCAs) are excited at frequencies which are close to integer (m>2) multiples of their natural resonance frequency, the bifurcation structure of the UCA oscillations as a function of pressure may be characterized by 3 general distinct regions. The UCA behavior starts with initial period one oscillations which undergoes a saddle node bifurcation to m coexisting attractors for an acoustic pressure above a threshold, P. Further increasing the pressure above a second threshold P, is followed by a sudden transition to period 1 oscillations.

Myosin gene expression and protein abundance in different castes of the Formosan subterranean termite (Coptotermes formosanus)

USDA-ARS?s Scientific Manuscript database

The Formosan subterranean termite (Coptotermes formosanus) is an important worldwide pest, each year causing millions of dollars in structural damage and control costs. Termite colonies are composed of several phenotypically distinct castes. Termites utilize these multiple castes to efficiently perf...

Influences of environment and disturbance on forest patterns in coastal Oregon watersheds.

Treesearch

Michael C. Wimberly; Thomas A. Spies

2001-01-01

Modern ecology often emphasizes the distinction between traditional theories of stable, environmentally structured communities and a new paradigm of disturbance driven, nonequilibrium dynamics. However, multiple hypotheses for observed vegetation patterns have seldom been explicitly tested. We used multivariate statistics and variation partitioning methods to assess...

Self-assembly programming of DNA polyominoes.

PubMed

Ong, Hui San; Syafiq-Rahim, Mohd; Kasim, Noor Hayaty Abu; Firdaus-Raih, Mohd; Ramlan, Effirul Ikhwan

2016-10-20

Fabrication of functional DNA nanostructures operating at a cellular level has been accomplished through molecular programming techniques such as DNA origami and single-stranded tiles (SST). During implementation, restrictive and constraint dependent designs are enforced to ensure conformity is attainable. We propose a concept of DNA polyominoes that promotes flexibility in molecular programming. The fabrication of complex structures is achieved through self-assembly of distinct heterogeneous shapes (i.e., self-organised optimisation among competing DNA basic shapes) with total flexibility during the design and assembly phases. In this study, the plausibility of the approach is validated using the formation of multiple 3×4 DNA network fabricated from five basic DNA shapes with distinct configurations (monomino, tromino and tetrominoes). Computational tools to aid the design of compatible DNA shapes and the structure assembly assessment are presented. The formations of the desired structures were validated using Atomic Force Microscopy (AFM) imagery. Five 3×4 DNA networks were successfully constructed using combinatorics of these five distinct DNA heterogeneous shapes. Our findings revealed that the construction of DNA supra-structures could be achieved using a more natural-like orchestration as compared to the rigid and restrictive conventional approaches adopted previously. Copyright © 2016 Elsevier B.V. All rights reserved.

Seismic isolation systems with distinct multiple frequencies

DOEpatents

Wu, Ting-shu; Seidensticker, Ralph W.

1990-01-01

A method and apparatus for isolating a building or other structure from smic vibratory motion which provides increased assurance that large horizontal motion of the structure will not occur than is provided by other isolation systems. Increased assurance that large horizontal motion will not occur is achieved by providing for change of the natural frequency of the support and structure system in response to displacement of the structure beyond a predetermined value. The natural frequency of the support and structure system may be achieved by providing for engaging and disengaging of the structure and some supporting members in response to motion of the supported structure.

The Multiple Subfunctions of Attention: Differential Developmental Gateways to Literacy and Numeracy

ERIC Educational Resources Information Center

Steele, Ann; Karmiloff-Smith, Annette; Cornish, Kim; Scerif, Gaia

2012-01-01

Attention is construed as multicomponential, but the roles of its distinct subfunctions in shaping the broader developing cognitive landscape are poorly understood. The current study assessed 3- to 6-year-olds (N = 83) to: (a) trace developmental trajectories of attentional processes and their structure in early childhood and (b) measure the…

Migration, Remittances and Educational Stratification among Blacks in Apartheid and Post-Apartheid South Africa

ERIC Educational Resources Information Center

Lu, Yao; Treiman, Donald J.

2011-01-01

This article extends previous work on family structure and children's education by conceptualizing migration as a distinct form of family disruption that reduces parental input but brings substantial economic benefits through remittances. It examines the multiple and countervailing effects of migration on schooling in the context of substantial…

The Latent Classes of Subclinical ADHD Symptoms: Convergences of Multiple Informant Reports

ERIC Educational Resources Information Center

Kobor, Andrea; Takacs, Adam; Urban, Robert; Csepe, Valeria

2012-01-01

The purpose of the present study was to conduct latent class analysis on the Hyperactivity scale of the Strengths and Difficulties Questionnaire in order to identify distinct subgroups of subclinical ADHD in a multi-informant framework. We hypothesized a similar structure between teachers and parents, and differences in symptom severity across…

Persistence of Multiple Genetic Lineages within Intrahost Populations of Ross River Virus▿

PubMed Central

Liu, Wen J.; Rourke, Michelle F.; Holmes, Edward C.; Aaskov, John G.

2011-01-01

We examined the structure and extent of genetic diversity in intrahost populations of Ross River virus (RRV) in samples from six human patients, focusing on the nonstructural (nsP3) and structural (E2) protein genes. Strikingly, although the samples were collected from contrasting ecological settings 3,000 kilometers apart in Australia, we observed multiple viral lineages in four of the six individuals, which is indicative of widespread mixed infections. In addition, a comparison with previously published RRV sequences revealed that these distinct lineages have been in circulation for at least 5 years, and we were able to document their long-term persistence over extensive geographical distances. PMID:21430052

SOLAR MULTIPLE ERUPTIONS FROM A CONFINED MAGNETIC STRUCTURE

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

Lee, Jeongwoo; Chae, Jongchul; Liu, Chang

2016-09-20

How eruption can recur from a confined magnetic structure is discussed based on the Solar Dynamics Observatory observations of the NOAA active region 11444, which produced three eruptions within 1.5 hr on 2012 March 27. The active region (AR) had the positive-polarity magnetic fields in the center surrounded by the negative-polarity fields around. Since such a distribution of magnetic polarity tends to form a dome-like magnetic fan structure confined over the AR, the multiple eruptions were puzzling. Our investigation reveals that this event exhibits several properties distinct from other eruptions associated with magnetic fan structures: (i) a long filament encirclingmore » the AR was present before the eruptions; (ii) expansion of the open–closed boundary (OCB) of the field lines after each eruption was suggestive of the growing fan-dome structure, and (iii) the ribbons inside the closed magnetic polarity inversion line evolved in response to the expanding OCB. It thus appears that in spite of multiple eruptions the fan-dome structure remained undamaged, and the closing back field lines after each eruption rather reinforced the fan-dome structure. We argue that the multiple eruptions could occur in this AR in spite of its confined magnetic structure because the filament encircling the AR was adequate for slipping through the magnetic separatrix to minimize the damage to its overlying fan-dome structure. The result of this study provides a new insight into the productivity of eruptions from a confined magnetic structure.« less

Protein kinases are associated with multiple, distinct cytoplasmic granules in quiescent yeast cells.

PubMed

Shah, Khyati H; Nostramo, Regina; Zhang, Bo; Varia, Sapna N; Klett, Bethany M; Herman, Paul K

2014-12-01

The cytoplasm of the eukaryotic cell is subdivided into distinct functional domains by the presence of a variety of membrane-bound organelles. The remaining aqueous space may be further partitioned by the regulated assembly of discrete ribonucleoprotein (RNP) complexes that contain particular proteins and messenger RNAs. These RNP granules are conserved structures whose importance is highlighted by studies linking them to human disorders like amyotrophic lateral sclerosis. However, relatively little is known about the diversity, composition, and physiological roles of these cytoplasmic structures. To begin to address these issues, we examined the cytoplasmic granules formed by a key set of signaling molecules, the protein kinases of the budding yeast Saccharomyces cerevisiae. Interestingly, a significant fraction of these proteins, almost 20%, was recruited to cytoplasmic foci specifically as cells entered into the G0-like quiescent state, stationary phase. Colocalization studies demonstrated that these foci corresponded to eight different granules, including four that had not been reported previously. All of these granules were found to rapidly disassemble upon the resumption of growth, and the presence of each was correlated with cell viability in the quiescent cultures. Finally, this work also identified new constituents of known RNP granules, including the well-characterized processing body and stress granule. The composition of these latter structures is therefore more varied than previously thought and could be an indicator of additional biological activities being associated with these complexes. Altogether, these observations indicate that quiescent yeast cells contain multiple distinct cytoplasmic granules that may make important contributions to their long-term survival. Copyright © 2014 by the Genetics Society of America.

Band structure and unconventional electronic topology of CoSi

NASA Astrophysics Data System (ADS)

Pshenay-Severin, D. A.; Ivanov, Y. V.; Burkov, A. A.; Burkov, A. T.

2018-04-01

Semimetals with certain crystal symmetries may possess unusual electronic structure topology, distinct from that of the conventional Weyl and Dirac semimetals. Characteristic property of these materials is the existence of band-touching points with multiple (higher than two-fold) degeneracy and nonzero Chern number. CoSi is a representative of this group of materials exhibiting the so-called ‘new fermions’. We report on an ab initio calculation of the electronic structure of CoSi using density functional methods, taking into account the spin-orbit interactions. The linearized \

Distinct Conformations of Ly49 Natural Killer Cell Receptors Mediate MHC Class I Recognition in Trans and Cis

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

Back, J.; Malchiodi, E; Cho, S

2009-01-01

Certain cell-surface receptors engage ligands expressed on juxtaposed cells and ligands on the same cell. The structural basis for trans versus cis binding is not known. Here, we showed that Ly49 natural killer (NK) cell receptors bound two MHC class I (MHC-I) molecules in trans when the two ligand-binding domains were backfolded onto the long stalk region. In contrast, dissociation of the ligand-binding domains from the stalk and their reorientation relative to the NK cell membrane allowed monovalent binding of MHC-I in cis. The distinct conformations (backfolded and extended) define the structural basis for cis-trans binding by Ly49 receptors andmore » explain the divergent functional consequences of cis versus trans interactions. Further analyses identified specific stalk segments that were not required for MHC-I binding in trans but were essential for inhibitory receptor function. These data identify multiple distinct roles of stalk regions for receptor function.« less

Interfaces between hexagonal and cubic oxides and their structure alternatives

DOE PAGES

Zhou, Hua; Wu, Lijun; Wang, Hui-Qiong; ...

2017-11-14

Multi-layer structure of functional materials often involves the integration of different crystalline phases. The film growth orientation thus frequently exhibits a transformation, owing to multiple possibilities caused by incompatible in-plane structural symmetry. Nevertheless, the detailed mechanism of the transformation has not yet been fully explored. Here we thoroughly probe the heteroepitaxially grown hexagonal zinc oxide (ZnO) films on cubic (001)-magnesium oxide (MgO) substrates using advanced scanning transition electron microscopy, X-ray diffraction and first principles calculations, revealing two distinct interface models of (001) ZnO/(001) MgO and (100) ZnO/(001) MgO. Here we have found that the structure alternatives are controlled thermodynamically bymore » the nucleation, while kinetically by the enhanced Zn adsorption and O diffusion upon the phase transformation. Finally, this work not only provides a guideline for the interface fabrication with distinct crystalline phases but also shows how polar and non-polar hexagonal ZnO films might be manipulated on the same cubic substrate.« less

Tunable valley polarization by a gate voltage when an electron tunnels through multiple line defects in graphene.

PubMed

Liu, Zhe; Jiang, Liwei; Zheng, Yisong

2015-02-04

By means of an appropriate wave function connection condition, we study the electronic structure of a line defect superlattice of graphene with the Dirac equation method. We obtain the analytical dispersion relation, which can simulate well the tight-binding numerical result about the band structure of the superlattice. Then, we generalize this theoretical method to study the electronic transmission through a potential barrier where multiple line defects are periodically patterned. We find that there exists a critical incident angle which restricts the electronic transmission through multiple line defects within a specific incident angle range. The critical angle depends sensitively on the potential barrier height, which can be modulated by a gate voltage. As a result, non-trivial transmissions of K and K' valley electrons are restricted, respectively, in two distinct ranges of the incident angle. Our theoretical result demonstrates that a gate voltage can act as a feasible measure to tune the valley polarization when electrons tunnel through multiple line defects.

Everyday distinction and omnivorous orientation: An analysis of food choice, attitudinal dispositions and social background.

PubMed

Kahma, Nina; Niva, Mari; Helakorpi, Satu; Jallinoja, Piia

2016-01-01

In recent years studies on cultural consumption have experienced a Bourdieusian renaissance. This is indicated by a growing body of research analysing distinctions in different areas of culture, and numerous studies on the homology thesis applying the concepts of distinction, field and capital. Concurrently, however, it has been argued that instead of distinctive tastes, distinction and class status are increasingly manifested by cultural omnivorousness. For a good part studies focussing on distinction in food have analysed eating out and stylization through restaurant preferences, rather than everyday food choices. In this article we investigate everyday food choices from the perspective of distinction and omnivorousness. Our analysis draws on cross-sectional quantitative data collected in 2012 among 15-64-year-old Finns (N = 2601). The article maps out the relationship between food choice frequencies, dispositions and social background with Multiple Correspondence Analysis (MCA). The results show that the consumption of fruit and vegetables, ready-meals and convenience foods were among the most divisive food choices. The first structuring dimension juxtaposed processed, fatty and sugared foods with unprocessed foods and fresh ingredients. This dimension was associated with healthiness and weight control as dispositions. On the second structuring dimension there were differences in the valuation of taste, pleasure and sociability, and a contrast between moderate and restrictive choices. Particularly the first dimension was associated with educational, occupational, and gender differences. Distinction within everyday food choices was manifested in the use of healthy and unprocessed foods and 'moderate hedonism' in contrast to more restrictive tastes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sequence harmony: detecting functional specificity from alignments

PubMed Central

Feenstra, K. Anton; Pirovano, Walter; Krab, Klaas; Heringa, Jaap

2007-01-01

Multiple sequence alignments are often used for the identification of key specificity-determining residues within protein families. We present a web server implementation of the Sequence Harmony (SH) method previously introduced. SH accurately detects subfamily specific positions from a multiple alignment by scoring compositional differences between subfamilies, without imposing conservation. The SH web server allows a quick selection of subtype specific sites from a multiple alignment given a subfamily grouping. In addition, it allows the predicted sites to be directly mapped onto a protein structure and displayed. We demonstrate the use of the SH server using the family of plant mitochondrial alternative oxidases (AOX). In addition, we illustrate the usefulness of combining sequence and structural information by showing that the predicted sites are clustered into a few distinct regions in an AOX homology model. The SH web server can be accessed at www.ibi.vu.nl/programs/seqharmwww. PMID:17584793

Characterization of two distinct beta2-microglobulin unfolding intermediates that may lead to amyloid fibrils of different morphology.

PubMed

Armen, Roger S; Daggett, Valerie

2005-12-13

The self-assembly of beta(2)-microglobulin into fibrils leads to dialysis-related amyloidosis. pH-mediated partial unfolding is required for the formation of the amyloidogenic intermediate that then self-assembles into amyloid fibrils. Two partially folded intermediates of beta(2)-microglobulin have been identified experimentally and linked to the formation of fibrils of distinct morphology, yet it remains difficult to characterize these partially unfolded states at high resolution using experimental approaches. Consequently, we have performed molecular dynamics simulations at neutral and low pH to determine the structures of these partially unfolded amyloidogenic intermediates. In the low-pH simulations, we observed the formation of alpha-sheet structure, which was first proposed by Pauling and Corey. Multiple simulations were performed, and two distinct intermediate state ensembles were identified that may account for the different fibril morphologies. The predominant early unfolding intermediate was nativelike in structure, in agreement with previous NMR studies. The late unfolding intermediate was significantly disordered, but it maintained an extended elongated structure, with hydrophobic clusters and residual alpha-extended chain strands in specific regions of the sequence that map to amyloidogenic peptides. We propose that the formation of alpha-sheet facilitates self-assembly into partially unfolded prefibrillar amyloidogenic intermediates.

Bacterial effectors target the common signaling partner BAK1 to disrupt multiple MAMP receptor-signaling complexes and impede plant immunity.

PubMed

Shan, Libo; He, Ping; Li, Jianming; Heese, Antje; Peck, Scott C; Nürnberger, Thorsten; Martin, Gregory B; Sheen, Jen

2008-07-17

Successful pathogens have evolved strategies to interfere with host immune systems. For example, the ubiquitous plant pathogen Pseudomonas syringae injects two sequence-distinct effectors, AvrPto and AvrPtoB, to intercept convergent innate immune responses stimulated by multiple microbe-associated molecular patterns (MAMPs). However, the direct host targets and precise molecular mechanisms of bacterial effectors remain largely obscure. We show that AvrPto and AvrPtoB bind the Arabidopsis receptor-like kinase BAK1, a shared signaling partner of both the flagellin receptor FLS2 and the brassinosteroid receptor BRI1. This targeting interferes with ligand-dependent association of FLS2 with BAK1 during infection. It also impedes BAK1-dependent host immune responses to diverse other MAMPs and brassinosteroid signaling. Significantly, the structural basis of AvrPto-BAK1 interaction appears to be distinct from AvrPto-Pto association required for effector-triggered immunity. These findings uncover a unique strategy of bacterial pathogenesis where virulence effectors block signal transmission through a key common component of multiple MAMP-receptor complexes.

Diversity in recognition of glycans by F-type lectins and galectins: molecular, structural, and biophysical aspects

PubMed Central

Vasta, Gerardo R.; Ahmed, Hafiz; Bianchet, Mario A.; Fernández-Robledo, José A.; Amzel, L. Mario

2013-01-01

Although lectins are “hard-wired” in the germline, the presence of tandemly arrayed carbohydrate recognition domains (CRDs), of chimeric structures displaying distinct CRDs, of polymorphic genes resulting in multiple isoforms, and in some cases, of a considerable recognition plasticity of their carbohydrate binding sites, significantly expand the lectin ligand-recognition spectrum and lectin functional diversification. Analysis of structural/functional aspects of galectins and F-lectins—the most recently identified lectin family characterized by a unique CRD sequence motif (a distinctive structural fold) and nominal specificity for l-Fuc—has led to a greater understanding of self/nonself recognition by proteins with tandemly arrayed CRDs. For lectins with a single CRD, however, recognition of self and nonself glycans can only be rationalized in terms of protein oligomerization and ligand clustering and presentation. Spatial and temporal changes in lectin expression, secretion, and local concentrations in extracellular microenvironments, as well as structural diversity and spatial display of their carbohydrate ligands on the host or microbial cell surface, are suggestive of a dynamic interplay of their recognition and effector functions in development and immunity. PMID:22973821

Biochemical and Structural Analysis of an Eis Family Aminoglycoside Acetyltransferase from Bacillus anthracis

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

Green, Keith D.; Biswas, Tapan; Chang, Changsoo

Proteins from the enhanced intracellular survival (Eis) family are versatile acetyltransferases that acetylate amines at multiple positions of several aminoglycosides (AGs). Their upregulation confers drug resistance. Homologues of Eis are present in diverse bacteria, including many pathogens. Eis from Mycobacterium tuberculosis (Eis_Mtb) has been well characterized. In this study, we explored the AG specificity and catalytic efficiency of the Eis family protein from Bacillus anthracis (Eis_Ban). Kinetic analysis of specificity and catalytic efficiency of acetylation of six AGs indicates that Eis_Ban displays significant differences from Eis_Mtb in both substrate binding and catalytic efficiency. The number of acetylated amines was alsomore » different for several AGs, indicating a distinct regiospecificity of Eis_Ban. Furthermore, most recently identified inhibitors of Eis_Mtb did not inhibit Eis_Ban, underscoring the differences between these two enzymes. To explain these differences, we determined an Eis_Ban crystal structure. The comparison of the crystal structures of Eis_Ban and Eis_Mtb demonstrates that critical residues lining their respective substrate binding pockets differ substantially, explaining their distinct specificities. Our results suggest that acetyltransferases of the Eis family evolved divergently to garner distinct specificities while conserving catalytic efficiency, possibly to counter distinct chemical challenges. The unique specificity features of these enzymes can be utilized as tools for developing AGs with novel modifications and help guide specific AG treatments to avoid Eis-mediated resistance.« less

Exploring the Underlying Components of Primary School Teachers' Pedagogical Content Knowledge for Technology Education

ERIC Educational Resources Information Center

Rohaan, Ellen J.; Taconis, Ruurd; Jochems, Wim M. G.

2011-01-01

In the study described in this article, primary school teachers' pedagogical content knowledge (PCK) of technology education was measured with a multiple choice test; the Teaching of Technology Test (TTT). The aim of the study was to explore the latent factor structure of PCK, which is considered to be a crucial and distinctive domain of teacher…

Defining how aging Pseudotsuga and Abies compensate for multiple stresses through multi-criteria assessment of a functional-structural model

Treesearch

Maureen C. Kennedy; E. David Ford; Thomas M. Hinckley

2009-01-01

Many hypotheses have been advanced about factors that control tree longevity. We use a simulation model with multi-criteria optimization and Pareto optimality to determine branch morphologies in the Pinaceae that minimize the effect of growth limitations due to water stress while simultaneously maximizing carbohydrate gain. Two distinct branch morphologies in the...

Unifying Inference of Meso-Scale Structures in Networks.

PubMed

Tunç, Birkan; Verma, Ragini

2015-01-01

Networks are among the most prevalent formal representations in scientific studies, employed to depict interactions between objects such as molecules, neuronal clusters, or social groups. Studies performed at meso-scale that involve grouping of objects based on their distinctive interaction patterns form one of the main lines of investigation in network science. In a social network, for instance, meso-scale structures can correspond to isolated social groupings or groups of individuals that serve as a communication core. Currently, the research on different meso-scale structures such as community and core-periphery structures has been conducted via independent approaches, which precludes the possibility of an algorithmic design that can handle multiple meso-scale structures and deciding which structure explains the observed data better. In this study, we propose a unified formulation for the algorithmic detection and analysis of different meso-scale structures. This facilitates the investigation of hybrid structures that capture the interplay between multiple meso-scale structures and statistical comparison of competing structures, all of which have been hitherto unavailable. We demonstrate the applicability of the methodology in analyzing the human brain network, by determining the dominant organizational structure (communities) of the brain, as well as its auxiliary characteristics (core-periphery).

Widom Lines in Binary Mixtures of Supercritical Fluids.

PubMed

Raju, Muralikrishna; Banuti, Daniel T; Ma, Peter C; Ihme, Matthias

2017-06-08

Recent experiments on pure fluids have identified distinct liquid-like and gas-like regimes even under supercritical conditions. The supercritical liquid-gas transition is marked by maxima in response functions that define a line emanating from the critical point, referred to as Widom line. However, the structure of analogous state transitions in mixtures of supercritical fluids has not been determined, and it is not clear whether a Widom line can be identified for binary mixtures. Here, we present first evidence for the existence of multiple Widom lines in binary mixtures from molecular dynamics simulations. By considering mixtures of noble gases, we show that, depending on the phase behavior, mixtures transition from a liquid-like to a gas-like regime via distinctly different pathways, leading to phase relationships of surprising complexity and variety. Specifically, we show that miscible binary mixtures have behavior analogous to a pure fluid and the supercritical state space is characterized by a single liquid-gas transition. In contrast, immiscible binary mixture undergo a phase separation in which the clusters transition separately at different temperatures, resulting in multiple distinct Widom lines. The presence of this unique transition behavior emphasizes the complexity of the supercritical state to be expected in high-order mixtures of practical relevance.

New Measurement for Correlation of Co-evolution Relationship of Subsequences in Protein.

PubMed

Gao, Hongyun; Yu, Xiaoqing; Dou, Yongchao; Wang, Jun

2015-12-01

Many computational tools have been developed to measure the protein residues co-evolution. Most of them only focus on co-evolution for pairwise residues in a protein sequence. However, number of residues participate in co-evolution might be multiple. And some co-evolved residues are clustered in several distinct regions in primary structure. Therefore, the co-evolution among the adjacent residues and the correlation between the distinct regions offer insights into function and evolution of the protein and residues. Subsequence is used to represent the adjacent multiple residues in one distinct region. In the paper, co-evolution relationship in each subsequence is represented by mutual information matrix (MIM). Then, Pearson's correlation coefficient: R value is developed to measure the similarity correlation of two MIMs. MSAs from Catalytic Data Base (Catalytic Site Atlas, CSA) are used for testing. R value characterizes a specific class of residues. In contrast to individual pairwise co-evolved residues, adjacent residues without high individual MI values are found since the co-evolved relationship among them is similar to that among another set of adjacent residues. These subsequences possess some flexibility in the composition of side chains, such as the catalyzed environment.

Delineating ecological regions in marine systems: Integrating physical structure and community composition to inform spatial management in the eastern Bering Sea

NASA Astrophysics Data System (ADS)

Baker, Matthew R.; Hollowed, Anne B.

2014-11-01

Characterizing spatial structure and delineating meaningful spatial boundaries have useful applications to understanding regional dynamics in marine systems, and are integral to ecosystem approaches to fisheries management. Physical structure and drivers combine with biological responses and interactions to organize marine systems in unique ways at multiple scales. We apply multivariate statistical methods to define spatially coherent ecological units or ecoregions in the eastern Bering Sea. We also illustrate a practical approach to integrate data on species distribution, habitat structure and physical forcing mechanisms to distinguish areas with distinct biogeography as one means to define management units in large marine ecosystems. We use random forests to quantify the relative importance of habitat and environmental variables to the distribution of individual species, and to quantify shifts in multispecies assemblages or community composition along environmental gradients. Threshold shifts in community composition are used to identify regions with distinct physical and biological attributes, and to evaluate the relative importance of predictor variables to determining regional boundaries. Depth, bottom temperature and frontal boundaries were dominant factors delineating distinct biological communities in this system, with a latitudinal divide at approximately 60°N. Our results indicate that distinct climatic periods will shift habitat gradients and that dynamic physical variables such as temperature and stratification are important to understanding temporal stability of ecoregion boundaries. We note distinct distribution patterns among functional guilds and also evidence for resource partitioning among individual species within each guild. By integrating physical and biological data to determine spatial patterns in community composition, we partition ecosystems along ecologically significant gradients. This may provide a basis for defining spatial management units or serve as a baseline index for analyses of structural shifts in the physical environment, species abundance and distribution, and community dynamics over time.

Function does not follow form in gene regulatory circuits.

PubMed

Payne, Joshua L; Wagner, Andreas

2015-08-20

Gene regulatory circuits are to the cell what arithmetic logic units are to the chip: fundamental components of information processing that map an input onto an output. Gene regulatory circuits come in many different forms, distinct structural configurations that determine who regulates whom. Studies that have focused on the gene expression patterns (functions) of circuits with a given structure (form) have examined just a few structures or gene expression patterns. Here, we use a computational model to exhaustively characterize the gene expression patterns of nearly 17 million three-gene circuits in order to systematically explore the relationship between circuit form and function. Three main conclusions emerge. First, function does not follow form. A circuit of any one structure can have between twelve and nearly thirty thousand distinct gene expression patterns. Second, and conversely, form does not follow function. Most gene expression patterns can be realized by more than one circuit structure. And third, multifunctionality severely constrains circuit form. The number of circuit structures able to drive multiple gene expression patterns decreases rapidly with the number of these patterns. These results indicate that it is generally not possible to infer circuit function from circuit form, or vice versa.

Structural controls on the megathrust segmentation of the Middle America Trench from multiple geophysical observations

NASA Astrophysics Data System (ADS)

Naif, S.; Bassett, D.

2016-12-01

Subduction zone megathrusts display complex seismogenic behaviors that vary at intra- and inter-margin scales. Many different physical properties have been proposed to be primarily responsible for this behavior, such as the composition of subducted sediments, the hydration state of the incoming oceanic plate, and the pore-fluid pressure at the plate interface. Here, we focus on the northern Middle America Trench and show that subducting plate structures control megathrust segmentation. We analyze multiple types of seafloor geophysical observations and compare them to the distinct behavioral and spatial characteristics of the 1992 Nicaragua (Mw7.6), 2012 El Salvador (Mw7.3), 2012 Guatemala (Mw7.4), and 2012 Costa Rica (Mw7.6) events. The residual topography, residual gravity, and magnetic anomaly structure of the incoming oceanic plate and forearc seafloor are correlated. The forearc is composed of multiple unique segments that are bounded by subducting fracture zones. These boundaries correlate with foreshock and aftershock seismicity and also coincide with the hypocenter of all four earthquakes. The relationship between observed structures, earthquake slip inversions, and radiated energy of the four large events will be discussed.

Hamming and Accumulator Codes Concatenated with MPSK or QAM

NASA Technical Reports Server (NTRS)

Divsalar, Dariush; Dolinar, Samuel

2009-01-01

In a proposed coding-and-modulation scheme, a high-rate binary data stream would be processed as follows: 1. The input bit stream would be demultiplexed into multiple bit streams. 2. The multiple bit streams would be processed simultaneously into a high-rate outer Hamming code that would comprise multiple short constituent Hamming codes a distinct constituent Hamming code for each stream. 3. The streams would be interleaved. The interleaver would have a block structure that would facilitate parallelization for high-speed decoding. 4. The interleaved streams would be further processed simultaneously into an inner two-state, rate-1 accumulator code that would comprise multiple constituent accumulator codes - a distinct accumulator code for each stream. 5. The resulting bit streams would be mapped into symbols to be transmitted by use of a higher-order modulation - for example, M-ary phase-shift keying (MPSK) or quadrature amplitude modulation (QAM). The novelty of the scheme lies in the concatenation of the multiple-constituent Hamming and accumulator codes and the corresponding parallel architectures of the encoder and decoder circuitry (see figure) needed to process the multiple bit streams simultaneously. As in the cases of other parallel-processing schemes, one advantage of this scheme is that the overall data rate could be much greater than the data rate of each encoder and decoder stream and, hence, the encoder and decoder could handle data at an overall rate beyond the capability of the individual encoder and decoder circuits.

Characterization of Cell Surface and EPS Remodeling of Azospirillum brasilense Chemotaxis-like 1 Signal Transduction Pathway mutants by Atomic Force Microscopy

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

Billings, Amanda N; Siuti, Piro; Bible, Amber

2011-01-01

To compete in complex microbial communities, bacteria must quickly sense environmental changes and adjust cellular functions for optimal growth. Chemotaxis-like signal transduction pathways are implicated in the modulation of multiple cellular responses, including motility, EPS production, and cell-to-cell interactions. Recently, the Che1 chemotaxis-like pathway from Azospirillum brasilense was shown to modulate flocculation. In A. brasilense, cell surface properties, including EPS production, are thought to play a direct role in promoting flocculation. Using atomic force microscopy (AFM), we have detected distinct changes in the surface morphology of flocculating A. brasilense Che1 mutant strains that are absent in the wild type strain.more » Whereas the wild type strain produces a smooth mucosal extracellular matrix, the flocculating Che1 mutant strains produce distinctive extracellular fibril structures. Further analyses using flocculation inhibition and lectin-binding assays suggest that the composition of EPS components in the extracellular matrix differs between the cheA1 and cheY1 mutants, despite an apparent similarity in the macroscopic floc structures. Collectively, these data indicate that mutations in the Che1 pathway that result in increased flocculation are correlated with distinctive changes in the extracellular matrix structure produced by the mutants, including likely changes in the EPS structure and/or composition.« less

Phospho-selective mechanisms of arrestin conformations and functions revealed by unnatural amino acid incorporation and 19F-NMR

PubMed Central

Yang, Fan; Yu, Xiao; Liu, Chuan; Qu, Chang-Xiu; Gong, Zheng; Liu, Hong-Da; Li, Fa-Hui; Wang, Hong-Mei; He, Dong-Fang; Yi, Fan; Song, Chen; Tian, Chang-Lin; Xiao, Kun-Hong; Wang, Jiang-Yun; Sun, Jin-Peng

2015-01-01

Specific arrestin conformations are coupled to distinct downstream effectors, which underlie the functions of many G-protein-coupled receptors (GPCRs). Here, using unnatural amino acid incorporation and fluorine-19 nuclear magnetic resonance (19F-NMR) spectroscopy, we demonstrate that distinct receptor phospho-barcodes are translated to specific β-arrestin-1 conformations and direct selective signalling. With its phosphate-binding concave surface, β-arrestin-1 ‘reads' the message in the receptor phospho-C-tails and distinct phospho-interaction patterns are revealed by 19F-NMR. Whereas all functional phosphopeptides interact with a common phosphate binding site and induce the movements of finger and middle loops, different phospho-interaction patterns induce distinct structural states of β-arrestin-1 that are coupled to distinct arrestin functions. Only clathrin recognizes and stabilizes GRK2-specific β-arrestin-1 conformations. The identified receptor-phospho-selective mechanism for arrestin conformation and the spacing of the multiple phosphate-binding sites in the arrestin enable arrestin to recognize plethora phosphorylation states of numerous GPCRs, contributing to the functional diversity of receptors. PMID:26347956

Structural basis for the antifolding activity of a molecular chaperone

NASA Astrophysics Data System (ADS)

Huang, Chengdong; Rossi, Paolo; Saio, Tomohide; Kalodimos, Charalampos G.

2016-09-01

Molecular chaperones act on non-native proteins in the cell to prevent their aggregation, premature folding or misfolding. Different chaperones often exert distinct effects, such as acceleration or delay of folding, on client proteins via mechanisms that are poorly understood. Here we report the solution structure of SecB, a chaperone that exhibits strong antifolding activity, in complex with alkaline phosphatase and maltose-binding protein captured in their unfolded states. SecB uses long hydrophobic grooves that run around its disk-like shape to recognize and bind to multiple hydrophobic segments across the length of non-native proteins. The multivalent binding mode results in proteins wrapping around SecB. This unique complex architecture alters the kinetics of protein binding to SecB and confers strong antifolding activity on the chaperone. The data show how the different architectures of chaperones result in distinct binding modes with non-native proteins that ultimately define the activity of the chaperone.

4-Nitro styrylquinoline is an antimalarial inhibiting multiple stages of Plasmodium falciparum asexual life cycle.

PubMed

Roberts, Bracken F; Zheng, Yongsheng; Cleaveleand, Jacob; Lee, Sukjun; Lee, Eunyoung; Ayong, Lawrence; Yuan, Yu; Chakrabarti, Debopam

2017-04-01

Drugs against malaria are losing their effectiveness because of emerging drug resistance. This underscores the need for novel therapeutic options for malaria with mechanism of actions distinct from current antimalarials. To identify novel pharmacophores against malaria we have screened compounds containing structural features of natural products that are pharmacologically relevant. This screening has identified a 4-nitro styrylquinoline (SQ) compound with submicromolar antiplasmodial activity and excellent selectivity. SQ exhibits a cellular action distinct from current antimalarials, acting early on malaria parasite's intraerythrocytic life cycle including merozoite invasion. The compound is a fast-acting parasitocidal agent and also exhibits curative property in the rodent malaria model when administered orally. In this report, we describe the synthesis, preliminary structure-function analysis, and the parasite developmental stage specific action of the SQ scaffold. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Phylogeographic and population genetic analyses reveal multiple species of Boa and independent origins of insular dwarfism.

PubMed

Card, Daren C; Schield, Drew R; Adams, Richard H; Corbin, Andrew B; Perry, Blair W; Andrew, Audra L; Pasquesi, Giulia I M; Smith, Eric N; Jezkova, Tereza; Boback, Scott M; Booth, Warren; Castoe, Todd A

2016-09-01

Boa is a Neotropical genus of snakes historically recognized as monotypic despite its expansive distribution. The distinct morphological traits and color patterns exhibited by these snakes, together with the wide diversity of ecosystems they inhabit, collectively suggest that the genus may represent multiple species. Morphological variation within Boa also includes instances of dwarfism observed in multiple offshore island populations. Despite this substantial diversity, the systematics of the genus Boa has received little attention until very recently. In this study we examined the genetic structure and phylogenetic relationships of Boa populations using mitochondrial sequences and genome-wide SNP data obtained from RADseq. We analyzed these data at multiple geographic scales using a combination of phylogenetic inference (including coalescent-based species delimitation) and population genetic analyses. We identified extensive population structure across the range of the genus Boa and multiple lines of evidence for three widely-distributed clades roughly corresponding with the three primary land masses of the Western Hemisphere. We also find both mitochondrial and nuclear support for independent origins and parallel evolution of dwarfism on offshore island clusters in Belize and Cayos Cochinos Menor, Honduras. Copyright © 2016 Elsevier Inc. All rights reserved.

Hsp40 function in yeast prion propagation: Amyloid diversity necessitates chaperone functional complexity.

PubMed

Sporn, Zachary A; Hines, Justin K

2015-01-01

Yeast prions are heritable protein-based elements, most of which are formed of amyloid aggregates that rely on the action of molecular chaperones for transmission to progeny. Prions can form distinct amyloid structures, known as 'strains' in mammalian systems, that dictate both pathological progression and cross-species infection barriers. In yeast these same amyloid structural polymorphisms, called 'variants', dictate the intensity of prion-associated phenotypes and stability in mitosis. We recently reported that [PSI(+)] prion variants differ in the fundamental domain requirements for one chaperone, the Hsp40/J-protein Sis1, which are mutually exclusive between 2 different yeast prions, demonstrating a functional plurality for Sis1. Here we extend that analysis to incorporate additional data that collectively support the hypothesis that Sis1 has multiple functional roles that can be accomplished by distinct sets of domains. These functions are differentially required by distinct prions and prion variants. We also present new data regarding Hsp104-mediated prion elimination and show that some Sis1 functions, but not all, are conserved in the human homolog Hdj1/DNAJB1. Importantly, of the 10 amyloid-based prions indentified to date in Saccharomyces cerevisiae, the chaperone requirements of only 4 are known, leaving a great diversity of amyloid structures, and likely modes of amyloid-chaperone interaction, largely unexplored.

Hierarchical mixture of experts and diagnostic modeling approach to reduce hydrologic model structural uncertainty: STRUCTURAL UNCERTAINTY DIAGNOSTICS

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

Moges, Edom; Demissie, Yonas; Li, Hong-Yi

2016-04-01

In most water resources applications, a single model structure might be inadequate to capture the dynamic multi-scale interactions among different hydrological processes. Calibrating single models for dynamic catchments, where multiple dominant processes exist, can result in displacement of errors from structure to parameters, which in turn leads to over-correction and biased predictions. An alternative to a single model structure is to develop local expert structures that are effective in representing the dominant components of the hydrologic process and adaptively integrate them based on an indicator variable. In this study, the Hierarchical Mixture of Experts (HME) framework is applied to integratemore » expert model structures representing the different components of the hydrologic process. Various signature diagnostic analyses are used to assess the presence of multiple dominant processes and the adequacy of a single model, as well as to identify the structures of the expert models. The approaches are applied for two distinct catchments, the Guadalupe River (Texas) and the French Broad River (North Carolina) from the Model Parameter Estimation Experiment (MOPEX), using different structures of the HBV model. The results show that the HME approach has a better performance over the single model for the Guadalupe catchment, where multiple dominant processes are witnessed through diagnostic measures. Whereas, the diagnostics and aggregated performance measures prove that French Broad has a homogeneous catchment response, making the single model adequate to capture the response.« less

IR-IR Conformation Specific Spectroscopy of Na+(Glucose) Adducts

NASA Astrophysics Data System (ADS)

Voss, Jonathan M.; Kregel, Steven J.; Fischer, Kaitlyn C.; Garand, Etienne

2018-01-01

We report an IR-IR double resonance study of the structural landscape present in the Na+(glucose) complex. Our experimental approach involves minimal modifications to a typical IR predissociation setup, and can be carried out via ion-dip or isomer-burning methods, providing additional flexibility to suit different experimental needs. In the current study, the single-laser IR predissociation spectrum of Na+(glucose), which clearly indicates contributions from multiple structures, was experimentally disentangled to reveal the presence of three α-conformers and five β-conformers. Comparisons with calculations show that these eight conformations correspond to the lowest energy gas-phase structures with distinctive Na+ coordination. [Figure not available: see fulltext.

C. elegans Major Fats Are Stored in Vesicles Distinct from Lysosome-Related Organelles

PubMed Central

O’Rourke, Eyleen J.; Soukas, Alexander A.; Carr, Christopher E.; Ruvkun, Gary

2010-01-01

SUMMARY Genetic conservation allows ancient features of fat storage endocrine pathways to be explored in C. elegans. Multiple studies have used Nile red or BODIPY-labeled fatty acids to identify regulators of fat mass. When mixed with their food, E. coli bacteria, Nile red, and BODIPY-labeled fatty acids stain multiple spherical cellular structures in the C. elegans major fat storage organ, the intestine. However, here we demonstrate that, in the conditions previously reported, the lysosome-related organelles stained by Nile red and BODIPY-labeled fatty acids are not the C. elegans major fat storage compartment. We show that the major fat stores are contained in a distinct cellular compartment that is not stained by Nile red. Using biochemical assays, we validate oil red O staining as a method to assess major fat stores in C. elegans, allowing for efficient and accurate genetic and functional genomic screens for genes that control fat accumulation at the organismal level. PMID:19883620

Sensitivity to Heavy-Metal Ions of Unfolded Fullerene Quantum Dots

PubMed Central

Ciotta, Erica; Paoloni, Stefano; Richetta, Maria; Tagliatesta, Pietro; Lorecchio, Chiara; Casciardi, Stefano

2017-01-01

A novel type of graphene-like quantum dots, synthesized by oxidation and cage-opening of C60 buckminsterfullerene, has been studied as a fluorescent and absorptive probe for heavy-metal ions. The lattice structure of such unfolded fullerene quantum dots (UFQDs) is distinct from that of graphene since it includes both carbon hexagons and pentagons. The basic optical properties, however, are similar to those of regular graphene oxide quantum dots. On the other hand, UFQDs behave quite differently in the presence of heavy-metal ions, in that multiple sensitivity to Cu2+, Pb2+ and As(III) was observed through comparable quenching of the fluorescent emission and different variations of the transmittance spectrum. By dynamic light scattering measurements and transmission electron microscope (TEM) images we confirmed, for the first time in metal sensing, that this response is due to multiple complexation and subsequent aggregation of UFQDs. Nonetheless, the explanation of the distinct behaviour of transmittance in the presence of As(III) and the formation of precipitate with Pb2+ require further studies. These differences, however, also make it possible to discriminate between the three metal ions in view of the implementation of a selective multiple sensor. PMID:29135946

Multi-scale temporal and spatial variation in genotypic composition of Cladophora-borne Escherichia coli populations in Lake Michigan.

PubMed

Badgley, Brian D; Ferguson, John; Vanden Heuvel, Amy; Kleinheinz, Gregory T; McDermott, Colleen M; Sandrin, Todd R; Kinzelman, Julie; Junion, Emily A; Byappanahalli, Muruleedhara N; Whitman, Richard L; Sadowsky, Michael J

2011-01-01

High concentrations of Escherichia coli in mats of Cladophora in the Great Lakes have raised concern over the continued use of this bacterium as an indicator of microbial water quality. Determining the impacts of these environmentally abundant E. coli, however, necessitates a better understanding of their ecology. In this study, the population structure of 4285 Cladophora-borne E. coli isolates, obtained over multiple three day periods from Lake Michigan Cladophora mats in 2007-2009, was examined by using DNA fingerprint analyses. In contrast to previous studies that have been done using isolates from attached Cladophora obtained over large time scales and distances, the extensive sampling done here on free-floating mats over successive days at multiple sites provided a large dataset that allowed for a detailed examination of changes in population structure over a wide range of spatial and temporal scales. While Cladophora-borne E. coli populations were highly diverse and consisted of many unique isolates, multiple clonal groups were also present and accounted for approximately 33% of all isolates examined. Patterns in population structure were also evident. At the broadest scales, E. coli populations showed some temporal clustering when examined by year, but did not show good spatial distinction among sites. E. coli population structure also showed significant patterns at much finer temporal scales. Populations were distinct on an individual mat basis at a given site, and on individual days within a single mat. Results of these studies indicate that Cladophora-borne E. coli populations consist of a mixture of stable, and possibly naturalized, strains that persist during the life of the mat, and more unique, transient strains that can change over rapid time scales. It is clear that further study of microbial processes at fine spatial and temporal scales is needed, and that caution must be taken when interpolating short term microbial dynamics from results obtained from weekly or monthly samples. Copyright © 2010 Elsevier Ltd. All rights reserved.

Multi-scale temporal and spatial variation in genotypic composition of Cladophora-borne Escherichia coli populations in Lake Michigan

USGS Publications Warehouse

Badgley, B.D.; Ferguson, J.; Heuvel, A.V.; Kleinheinz, G.T.; McDermott, C.M.; Sandrin, T.R.; Kinzelman, J.; Junion, E.A.; Byappanahalli, M.N.; Whitman, R.L.; Sadowsky, M.J.

2011-01-01

High concentrations of Escherichia coli in mats of Cladophora in the Great Lakes have raised concern over the continued use of this bacterium as an indicator of microbial water quality. Determining the impacts of these environmentally abundant E. coli, however, necessitates a better understanding of their ecology. In this study, the population structure of 4285 Cladophora-borne E. coli isolates, obtained over multiple three day periods from Lake Michigan Cladophora mats in 2007-2009, was examined by using DNA fingerprint analyses. In contrast to previous studies that have been done using isolates from attached Cladophora obtained over large time scales and distances, the extensive sampling done here on free-floating mats over successive days at multiple sites provided a large dataset that allowed for a detailed examination of changes in population structure over a wide range of spatial and temporal scales. While Cladophora-borne E. coli populations were highly diverse and consisted of many unique isolates, multiple clonal groups were also present and accounted for approximately 33% of all isolates examined. Patterns in population structure were also evident. At the broadest scales, E. coli populations showed some temporal clustering when examined by year, but did not show good spatial distinction among sites. E. coli population structure also showed significant patterns at much finer temporal scales. Populations were distinct on an individual mat basis at a given site, and on individual days within a single mat. Results of these studies indicate that Cladophora-borne E. coli populations consist of a mixture of stable, and possibly naturalized, strains that persist during the life of the mat, and more unique, transient strains that can change over rapid time scales. It is clear that further study of microbial processes at fine spatial and temporal scales is needed, and that caution must be taken when interpolating short term microbial dynamics from results obtained from weekly or monthly samples.

Ultra-high aggregate bandwidth two-dimensional multiple-wavelength diode laser arrays

NASA Astrophysics Data System (ADS)

Chang-Hasnain, Connie

1994-04-01

Two-dimensional (2D) multi-wavelength vertical cavity surface emitting laser (VCSEL) arrays is promising for ultrahigh aggregate capacity optical networks. A 2D VCSEL array emitting 140 distinct wavelengths was reported by implementing a spatially graded layer in the VCSEL structure, which in turn creates a wavelength spread. In this program, we concentrated on novel epitaxial growth techniques to make reproducible and repeatable multi-wavelength VCSEL arrays.

Evolution at ‘Sutures’ and ‘Centers’: Recombination Can Aid Adaptation of Spatially Structured Populations on Rugged Fitness Landscapes

PubMed Central

Cooper, Jacob D.; Kerr, Benjamin

2016-01-01

Epistatic interactions among genes can give rise to rugged fitness landscapes, in which multiple “peaks” of high-fitness allele combinations are separated by “valleys” of low-fitness genotypes. How populations traverse rugged fitness landscapes is a long-standing question in evolutionary biology. Sexual reproduction may affect how a population moves within a rugged fitness landscape. Sex may generate new high-fitness genotypes by recombination, but it may also destroy high-fitness genotypes by shuffling the genes of a fit parent with a genetically distinct mate, creating low-fitness offspring. Either of these opposing aspects of sex require genotypic diversity in the population. Spatially structured populations may harbor more diversity than well-mixed populations, potentially amplifying both positive and negative effects of sex. On the other hand, spatial structure leads to clumping in which mating is more likely to occur between like types, diminishing the effects of recombination. In this study, we use computer simulations to investigate the combined effects of recombination and spatial structure on adaptation in rugged fitness landscapes. We find that spatially restricted mating and offspring dispersal may allow multiple genotypes inhabiting suboptimal peaks to coexist, and recombination at the “sutures” between the clusters of these genotypes can create genetically novel offspring. Sometimes such an offspring genotype inhabits a new peak on the fitness landscape. In such a case, spatially restricted mating allows this fledgling subpopulation to avoid recombination with distinct genotypes, as mates are more likely to be the same genotype. Such population “centers” can allow nascent peaks to establish despite recombination. Spatial structure may therefore allow an evolving population to enjoy the creative side of sexual recombination while avoiding its destructive side. PMID:27973606

Epigenomics and the concept of degeneracy in biological systems

PubMed Central

Mason, Paul H.; Barron, Andrew B.

2014-01-01

Researchers in the field of epigenomics are developing more nuanced understandings of biological complexity, and exploring the multiple pathways that lead to phenotypic expression. The concept of degeneracy—referring to the multiple pathways that a system recruits to achieve functional plasticity—is an important conceptual accompaniment to the growing body of knowledge in epigenomics. Distinct from degradation, redundancy and dilapidation; degeneracy refers to the plasticity of traits whose function overlaps in some environments, but diverges in others. While a redundant system is composed of repeated identical elements performing the same function, a degenerate system is composed of different elements performing similar or overlapping functions. Here, we describe the degenerate structure of gene regulatory systems from the basic genetic code to flexible epigenomic modifications, and discuss how these structural features have contributed to organism complexity, robustness, plasticity and evolvability. PMID:24335757

Evidence for multiple, distinct representations of the human body.

PubMed

Schwoebel, John; Coslett, H Branch

2005-04-01

Previous data from single-case and small group studies have suggested distinctions among structural, conceptual, and online sensorimotor representations of the human body. We developed a battery of tasks to further examine the prevalence and anatomic substrates of these body representations. The battery was administered to 70 stroke patients. Fifty-one percent of the patients were impaired relative to controls on at least one body representation measure. Further, principal components analysis of the patient data as well as direct comparisons of patient and control performance suggested a triple dissociation between measures of the 3 putative body representations. Consistent with previous distinctions between the "what" and "how" pathways, lesions of the left temporal lobe were most consistently associated with impaired performance on tasks assessing knowledge of the shape or lexical-semantic information about the body, whereas lesions of the dorsolateral frontal and parietal regions resulted in impaired performance on tasks requiring on-line coding of body posture.

The multiple subfunctions of attention: differential developmental gateways to literacy and numeracy.

PubMed

Steele, Ann; Karmiloff-Smith, Annette; Cornish, Kim; Scerif, Gaia

2012-11-01

Attention is construed as multicomponential, but the roles of its distinct subfunctions in shaping the broader developing cognitive landscape are poorly understood. The current study assessed 3- to 6-year-olds (N=83) to: (a) trace developmental trajectories of attentional processes and their structure in early childhood and (b) measure the impact of distinct attention subfunctions on concurrent and longitudinal abilities related to literacy and numeracy. Distinct trajectories across attention measures revealed the emergence of 2 attentional factors, encompassing "executive" and "sustained-selective" processes. Executive attention predicted concurrent abilities across domains at Time 1, whereas sustained-selective attention predicted basic numeracy 1 year later. These concurrent and longitudinal constraints cast a broader light on the unfolding relations between domain-general and domain-specific processes over early childhood. © 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.

Simple method for the generation of multiple homogeneous field volumes inside the bore of superconducting magnets.

PubMed

Chou, Ching-Yu; Ferrage, Fabien; Aubert, Guy; Sakellariou, Dimitris

2015-07-17

Standard Magnetic Resonance magnets produce a single homogeneous field volume, where the analysis is performed. Nonetheless, several modern applications could benefit from the generation of multiple homogeneous field volumes along the axis and inside the bore of the magnet. In this communication, we propose a straightforward method using a combination of ring structures of permanent magnets in order to cancel the gradient of the stray field in a series of distinct volumes. These concepts were demonstrated numerically on an experimentally measured magnetic field profile. We discuss advantages and limitations of our method and present the key steps required for an experimental validation.

Restricted amide rotation with steric hindrance induced multiple conformations

NASA Astrophysics Data System (ADS)

Krishnan, V. V.; Vazquez, Salvador; Maitra, Kalyani; Maitra, Santanu

2017-12-01

The Csbnd N bond character is dependent directly upon the resonance-contributor structure population driven by the delocalized nitrogen lone-pair of electrons. In the case of N, N-dibenzyl-ortho-toluamide (o-DBET), the molecule adopts subpopulations of conformers with distinct NMR spectral features, particularly at low temperatures. This conformational adaptation is unique to o-DBET, while the corresponding meta- and para- forms do not show such behavior. Variable-temperature (VT) NMR, two-dimensional exchange spectroscopy (EXSY), and qualitative molecular modeling studies are used to demonstrate how multiple competing interactions such as restricted amide rotation and steric hindrance effects can lead to versatile molecular adaptations in the solution state.

Molecular basis of the polydispersity of mucins: implications for the generation of saccharide diversity.

PubMed

Bhavanandan, V P; Gupta, D; Woitach, J; Guo, X; Jiang, W

1999-06-01

Secreted epithelial mucins are large macromolecules which exhibit extreme polydispersity, the molecular basis of which is not fully understood. We have obtained partial sequences of two genes (BSM1 and BSM2) coding for two distinct molecules. This is the first time that such closely-related genes have been identified for any mucin from an animal. We propose that a combination of multiple homologous genes, alternative splicing, differential glycosylation, and additional post-translational processing all contribute to the extreme polydispersity of mucins. The multiple domain structure and non-identical tandem repeats are also very important for the generation of the saccharide diversities of mucins.

A Recipe for Soft Fluidic Elastomer Robots

PubMed Central

Marchese, Andrew D.; Katzschmann, Robert K.

2015-01-01

Abstract This work provides approaches to designing and fabricating soft fluidic elastomer robots. That is, three viable actuator morphologies composed entirely from soft silicone rubber are explored, and these morphologies are differentiated by their internal channel structure, namely, ribbed, cylindrical, and pleated. Additionally, three distinct casting-based fabrication processes are explored: lamination-based casting, retractable-pin-based casting, and lost-wax-based casting. Furthermore, two ways of fabricating a multiple DOF robot are explored: casting the complete robot as a whole and casting single degree of freedom (DOF) segments with subsequent concatenation. We experimentally validate each soft actuator morphology and fabrication process by creating multiple physical soft robot prototypes. PMID:27625913

A Recipe for Soft Fluidic Elastomer Robots.

PubMed

Marchese, Andrew D; Katzschmann, Robert K; Rus, Daniela

2015-03-01

This work provides approaches to designing and fabricating soft fluidic elastomer robots. That is, three viable actuator morphologies composed entirely from soft silicone rubber are explored, and these morphologies are differentiated by their internal channel structure, namely, ribbed, cylindrical, and pleated. Additionally, three distinct casting-based fabrication processes are explored: lamination-based casting, retractable-pin-based casting, and lost-wax-based casting. Furthermore, two ways of fabricating a multiple DOF robot are explored: casting the complete robot as a whole and casting single degree of freedom (DOF) segments with subsequent concatenation. We experimentally validate each soft actuator morphology and fabrication process by creating multiple physical soft robot prototypes.

A convergent functional architecture of the insula emerges across imaging modalities.

PubMed

Kelly, Clare; Toro, Roberto; Di Martino, Adriana; Cox, Christine L; Bellec, Pierre; Castellanos, F Xavier; Milham, Michael P

2012-07-16

Empirical evidence increasingly supports the hypothesis that patterns of intrinsic functional connectivity (iFC) are sculpted by a history of evoked coactivation within distinct neuronal networks. This, together with evidence of strong correspondence among the networks defined by iFC and those delineated using a variety of other neuroimaging techniques, suggests a fundamental brain architecture detectable across multiple functional and structural imaging modalities. Here, we leverage this insight to examine the functional organization of the human insula. We parcellated the insula on the basis of three distinct neuroimaging modalities - task-evoked coactivation, intrinsic (i.e., task-independent) functional connectivity, and gray matter structural covariance. Clustering of these three different covariance-based measures revealed a convergent elemental organization of the insula that likely reflects a fundamental brain architecture governing both brain structure and function at multiple spatial scales. While not constrained to be hierarchical, our parcellation revealed a pseudo-hierarchical, multiscale organization that was consistent with previous clustering and meta-analytic studies of the insula. Finally, meta-analytic examination of the cognitive and behavioral domains associated with each of the insular clusters obtained elucidated the broad functional dissociations likely underlying the topography observed. To facilitate future investigations of insula function across healthy and pathological states, the insular parcels have been made freely available for download via http://fcon_1000.projects.nitrc.org, along with the analytic scripts used to perform the parcellations. Copyright © 2012 Elsevier Inc. All rights reserved.

Development of the Distinct Multiple Intelligences in Primary Students through Interest Centers

ERIC Educational Resources Information Center

Dueñas Macías, Fredy Alonso

2013-01-01

This article reports on an action research study that focused on developing the distinct multiple intelligences of an English class of fifth graders through interest centers at a Colombian school. A multiple intelligences questionnaire, an open-ended observation form, and a student mini-report sheet were used to collect data. Findings revealed…

Six-band terahertz metamaterial absorber based on the combination of multiple-order responses of metallic patches in a dual-layer stacked resonance structure.

PubMed

Wang, Ben-Xin; Wang, Gui-Zhen; Sang, Tian; Wang, Ling-Ling

2017-01-25

This paper reports on a numerical study of the six-band metamaterial absorber composed of two alternating stack of metallic-dielectric layers on top of a continuous metallic plane. Six obvious resonance peaks with high absorption performance (average larger than 99.37%) are realized. The first, third, fifth, and the second, fourth, sixth resonance absorption bands are attributed to the multiple-order responses (i.e., the 1-, 3- and 5-order responses) of the bottom- and top-layer of the structure, respectively, and thus the absorption mechanism of six-band absorber is due to the combination of two sets of the multiple-order resonances of these two layers. Besides, the size changes of the metallic layers have the ability to tune the frequencies of the six-band absorber. Employing the results, we also present a six-band polarization tunable absorber through varying the sizes of the structure in two orthogonal polarization directions. Moreover, nine-band terahertz absorber can be achieved by using a three-layer stacked structure. Simulation results indicate that the absorber possesses nine distinct resonance bands, and average absorptivities of them are larger than 94.03%. The six-band or nine-band absorbers obtained here have potential applications in many optoelectronic and engineering technology areas.

Structuring of Hydrogels across Multiple Length Scales for Biomedical Applications.

PubMed

Cooke, Megan E; Jones, Simon W; Ter Horst, Britt; Moiemen, Naiem; Snow, Martyn; Chouhan, Gurpreet; Hill, Lisa J; Esmaeli, Maryam; Moakes, Richard J A; Holton, James; Nandra, Rajpal; Williams, Richard L; Smith, Alan M; Grover, Liam M

2018-04-01

The development of new materials for clinical use is limited by an onerous regulatory framework, which means that taking a completely new material into the clinic can make translation economically unfeasible. One way to get around this issue is to structure materials that are already approved by the regulator, such that they exhibit very distinct physical properties and can be used in a broader range of clinical applications. Here, the focus is on the structuring of soft materials at multiple length scales by modifying processing conditions. By applying shear to newly forming materials, it is possible to trigger molecular reorganization of polymer chains, such that they aggregate to form particles and ribbon-like structures. These structures then weakly interact at zero shear forming a solid-like material. The resulting self-healing network is of particular use for a range of different biomedical applications. How these materials are used to allow the delivery of therapeutic entities (cells and proteins) and as a support for additive layer manufacturing of larger-scale tissue constructs is discussed. This technology enables the development of a range of novel materials and structures for tissue augmentation and regeneration. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ultra-Thin Multi-Band Polarization-Insensitive Microwave Metamaterial Absorber Based on Multiple-Order Responses Using a Single Resonator Structure

PubMed Central

Cheng, Zheng Ze; Mao, Xue Song; Gong, Rong Zhou

2017-01-01

We design an ultra-thin multi-band polarization-insensitive metamaterial absorber (MMA) using a single circular sector resonator (CSR) structure in the microwave region. Simulated results show that the proposed MMA has three distinctive absorption peaks at 3.35 GHz, 8.65 GHz, and 12.44 GHz, with absorbance of 98.8%, 99.7%, and 98.3%, respectively, which agree well with an experiment. Simulated surface current distributions of the unit-cell structure reveal that the triple-band absorption mainly originates from multiple-harmonic magnetic resonance. The proposed triple-band MMA can remain at a high absorption level for all polarization of both transverse-electric (TE) and transverse-magnetic (TM) modes under normal incidence. Moreover, by further optimizing the geometric parameters of the CSRs, four-band and five-band MMAs can also be obtained. Thus, our design will have potential application in detection, sensing, and stealth technology. PMID:29077036

Elucidating structural and molecular mechanisms of β-arrestin-biased agonism at GPCRs via MS-based proteomics.

PubMed

Xiao, Kunhong; Sun, Jinpeng

2018-01-01

The discovery of β-arrestin-dependent GPCR signaling has led to an exciting new field in GPCR pharmacology: to develop "biased agonists" that can selectively target a specific downstream signaling pathway that elicits beneficial therapeutic effects without activating other pathways that elicit negative side effects. This new trend in GPCR drug discovery requires us to understand the structural and molecular mechanisms of β-arrestin-biased agonism, which largely remain unclear. We have used cutting-edge mass spectrometry (MS)-based proteomics, combined with systems, chemical and structural biology to study protein function, macromolecular interaction, protein expression and posttranslational modifications in the β-arrestin-dependent GPCR signaling. These high-throughput proteomic studies have provided a systems view of β-arrestin-biased agonism from several perspectives: distinct receptor phosphorylation barcode, multiple receptor conformations, distinct β-arrestin conformations, and ligand-specific signaling. The information obtained from these studies offers new insights into the molecular basis of GPCR regulation by β-arrestin and provides a potential platform for developing novel therapeutic interventions through GPCRs. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Distinct bacterial assemblages reside at different depths in Arctic multiyear sea ice.

PubMed

Hatam, Ido; Charchuk, Rhianna; Lange, Benjamin; Beckers, Justin; Haas, Christian; Lanoil, Brian

2014-10-01

Bacterial communities in Arctic sea ice play an important role in the regulation of nutrient and energy dynamics in the Arctic Ocean. Sea ice has vertical gradients in temperature, brine salinity and volume, and light and UV levels. Multiyear ice (MYI) has at least two distinct ice layers: old fresh ice with limited permeability, and new saline ice, and may also include a surface melt pond layer. Here, we determine whether bacterial communities (1) differ with ice depth due to strong physical and chemical gradients, (2) are relatively homogenous within a layer, but differ between layers, or (3) do not vary with ice depth. Cores of MYI off northern Ellesmere Island, NU, Canada, were subsectioned in 30-cm intervals, and the bacterial assemblage structure was characterized using 16S rRNA gene pyrotag sequencing. Assemblages clustered into three distinct groups: top (0-30 cm); middle (30-150 cm); and bottom (150-236 cm). These layers correspond to the occurrence of refrozen melt pond ice, at least 2-year-old ice, and newly grown first-year ice at the bottom of the ice sheet, respectively. Thus, MYI houses multiple distinct bacterial assemblages, and in situ conditions appear to play a less important role in structuring microbial assemblages than the age or conditions of the ice at the time of formation. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

A distinct regulatory region of the Bmp5 locus activates gene expression following adult bone fracture or soft tissue injury.

PubMed

Guenther, Catherine A; Wang, Zhen; Li, Emma; Tran, Misha C; Logan, Catriona Y; Nusse, Roel; Pantalena-Filho, Luiz; Yang, George P; Kingsley, David M

2015-08-01

Bone morphogenetic proteins (BMPs) are key signaling molecules required for normal development of bones and other tissues. Previous studies have shown that null mutations in the mouse Bmp5 gene alter the size, shape and number of multiple bone and cartilage structures during development. Bmp5 mutations also delay healing of rib fractures in adult mutants, suggesting that the same signals used to pattern embryonic bone and cartilage are also reused during skeletal regeneration and repair. Despite intense interest in BMPs as agents for stimulating bone formation in clinical applications, little is known about the regulatory elements that control developmental or injury-induced BMP expression. To compare the DNA sequences that activate gene expression during embryonic bone formation and following acute injuries in adult animals, we assayed regions surrounding the Bmp5 gene for their ability to stimulate lacZ reporter gene expression in transgenic mice. Multiple genomic fragments, distributed across the Bmp5 locus, collectively coordinate expression in discrete anatomic domains during normal development, including in embryonic ribs. In contrast, a distinct regulatory region activated expression following rib fracture in adult animals. The same injury control region triggered gene expression in mesenchymal cells following tibia fracture, in migrating keratinocytes following dorsal skin wounding, and in regenerating epithelial cells following lung injury. The Bmp5 gene thus contains an "injury response" control region that is distinct from embryonic enhancers, and that is activated by multiple types of injury in adult animals. Copyright © 2015 Elsevier Inc. All rights reserved.

Identification of treatment responders based on multiple longitudinal outcomes with applications to multiple sclerosis patients.

PubMed

Kondo, Yumi; Zhao, Yinshan; Petkau, John

2017-05-30

Identification of treatment responders is a challenge in comparative studies where treatment efficacy is measured by multiple longitudinally collected continuous and count outcomes. Existing procedures often identify responders on the basis of only a single outcome. We propose a novel multiple longitudinal outcome mixture model that assumes that, conditionally on a cluster label, each longitudinal outcome is from a generalized linear mixed effect model. We utilize a Monte Carlo expectation-maximization algorithm to obtain the maximum likelihood estimates of our high-dimensional model and classify patients according to their estimated posterior probability of being a responder. We demonstrate the flexibility of our novel procedure on two multiple sclerosis clinical trial datasets with distinct data structures. Our simulation study shows that incorporating multiple outcomes improves the responder identification performance; this can occur even if some of the outcomes are ineffective. Our general procedure facilitates the identification of responders who are comprehensively defined by multiple outcomes from various distributions. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Mirror instability and origin of morningside auroral structure

NASA Technical Reports Server (NTRS)

Chiu, Y. T.; Schulz, M.; Fennell, J. F.; Kishi, A. M.

1983-01-01

Auroral optical imagery shows marked differences between auroral features of the evening and morning sectors: the separation between diffuse and discrete auroras in the evening sector is not distinct in the morning sector, which is dominated by auroral patches and multiple banded structures aligned along some direction. Plasma distribution function signatures also show marked differences: downward electron beams and inverted-V signatures prefer the evening sector, while the electron spectra on the morning sector are similar to the diffuse aurora. A theory of morningside auroras consistent with these features was constructed. The theory is based on modulation of the growth rates of electron cyclotron waves by the mirror instability, which is in turn driven by inward-convected ions that have become anisotropic. This modulation produces alternating bands of enhanced and reduced electron precipitation which approximate the observed multiple auroral bands and patches of the morning sector.

Computational and Statistical Analyses of Amino Acid Usage and Physico-Chemical Properties of the Twelve Late Embryogenesis Abundant Protein Classes

PubMed Central

Jaspard, Emmanuel; Macherel, David; Hunault, Gilles

2012-01-01

Late Embryogenesis Abundant Proteins (LEAPs) are ubiquitous proteins expected to play major roles in desiccation tolerance. Little is known about their structure - function relationships because of the scarcity of 3-D structures for LEAPs. The previous building of LEAPdb, a database dedicated to LEAPs from plants and other organisms, led to the classification of 710 LEAPs into 12 non-overlapping classes with distinct properties. Using this resource, numerous physico-chemical properties of LEAPs and amino acid usage by LEAPs have been computed and statistically analyzed, revealing distinctive features for each class. This unprecedented analysis allowed a rigorous characterization of the 12 LEAP classes, which differed also in multiple structural and physico-chemical features. Although most LEAPs can be predicted as intrinsically disordered proteins, the analysis indicates that LEAP class 7 (PF03168) and probably LEAP class 11 (PF04927) are natively folded proteins. This study thus provides a detailed description of the structural properties of this protein family opening the path toward further LEAP structure - function analysis. Finally, since each LEAP class can be clearly characterized by a unique set of physico-chemical properties, this will allow development of software to predict proteins as LEAPs. PMID:22615859

Point process models for localization and interdependence of punctate cellular structures.

PubMed

Li, Ying; Majarian, Timothy D; Naik, Armaghan W; Johnson, Gregory R; Murphy, Robert F

2016-07-01

Accurate representations of cellular organization for multiple eukaryotic cell types are required for creating predictive models of dynamic cellular function. To this end, we have previously developed the CellOrganizer platform, an open source system for generative modeling of cellular components from microscopy images. CellOrganizer models capture the inherent heterogeneity in the spatial distribution, size, and quantity of different components among a cell population. Furthermore, CellOrganizer can generate quantitatively realistic synthetic images that reflect the underlying cell population. A current focus of the project is to model the complex, interdependent nature of organelle localization. We built upon previous work on developing multiple non-parametric models of organelles or structures that show punctate patterns. The previous models described the relationships between the subcellular localization of puncta and the positions of cell and nuclear membranes and microtubules. We extend these models to consider the relationship to the endoplasmic reticulum (ER), and to consider the relationship between the positions of different puncta of the same type. Our results do not suggest that the punctate patterns we examined are dependent on ER position or inter- and intra-class proximity. With these results, we built classifiers to update previous assignments of proteins to one of 11 patterns in three distinct cell lines. Our generative models demonstrate the ability to construct statistically accurate representations of puncta localization from simple cellular markers in distinct cell types, capturing the complex phenomena of cellular structure interaction with little human input. This protocol represents a novel approach to vesicular protein annotation, a field that is often neglected in high-throughput microscopy. These results suggest that spatial point process models provide useful insight with respect to the spatial dependence between cellular structures. © 2016 International Society for Advancement of Cytometry. © 2016 International Society for Advancement of Cytometry.

Multiple intensity distributions from a single optical element

NASA Astrophysics Data System (ADS)

Berens, Michael; Bruneton, Adrien; Bäuerle, Axel; Traub, Martin; Wester, Rolf; Stollenwerk, Jochen; Loosen, Peter

2013-09-01

We report on an extension of the previously published two-step freeform optics tailoring algorithm using a Monge-Kantorovich mass transportation framework. The algorithm's ability to design multiple freeform surfaces allows for the inclusion of multiple distinct light paths and hence the implementation of multiple lighting functions in a single optical element. We demonstrate the procedure in the context of automotive lighting, in which a fog lamp and a daytime running lamp are integrated in a single optical element illuminated by two distinct groups of LEDs.

Genome-wide mapping of the RNA targets of the Pseudomonas aeruginosa riboregulatory protein RsmN.

PubMed

Romero, Manuel; Silistre, Hazel; Lovelock, Laura; Wright, Victoria J; Chan, Kok-Gan; Hong, Kar-Wai; Williams, Paul; Cámara, Miguel; Heeb, Stephan

2018-04-30

Pseudomonads typically carry multiple non-identical alleles of the post-transcriptional regulator rsmA. In Pseudomonas aeruginosa, RsmN is notable in that its structural rearrangement confers distinct and overlapping functions with RsmA. However, little is known about the specificities of RsmN for its target RNAs and overall impact on the biology of this pathogen. We purified and mapped 503 transcripts directly bound by RsmN in P. aeruginosa. About 200 of the mRNAs identified encode proteins of demonstrated function including some determining acute and chronic virulence traits. For example, RsmN reduces biofilm development both directly and indirectly via multiple pathways, involving control of Pel exopolysaccharide biosynthesis and c-di-GMP levels. The RsmN targets identified are also shared with RsmA, although deletion of rsmN generally results in less pronounced phenotypes than those observed for ΔrsmA or ΔrsmArsmNind mutants, probably as a consequence of different binding affinities. Targets newly identified for the Rsm system include the small non-coding RNA CrcZ involved in carbon catabolite repression, for which differential binding of RsmN and RsmA to specific CrcZ regions is demonstrated. The results presented here provide new insights into the intricacy of riboregulatory networks involving multiple but distinct RsmA homologues.

Programming Hierarchical Self-Assembly of Patchy Particles into Colloidal Crystals via Colloidal Molecules.

PubMed

Morphew, Daniel; Shaw, James; Avins, Christopher; Chakrabarti, Dwaipayan

2018-03-27

Colloidal self-assembly is a promising bottom-up route to a wide variety of three-dimensional structures, from clusters to crystals. Programming hierarchical self-assembly of colloidal building blocks, which can give rise to structures ordered at multiple levels to rival biological complexity, poses a multiscale design problem. Here we explore a generic design principle that exploits a hierarchy of interaction strengths and employ this design principle in computer simulations to demonstrate the hierarchical self-assembly of triblock patchy colloidal particles into two distinct colloidal crystals. We obtain cubic diamond and body-centered cubic crystals via distinct clusters of uniform size and shape, namely, tetrahedra and octahedra, respectively. Such a conceptual design framework has the potential to reliably encode hierarchical self-assembly of colloidal particles into a high level of sophistication. Moreover, the design framework underpins a bottom-up route to cubic diamond colloidal crystals, which have remained elusive despite being much sought after for their attractive photonic applications.

Simple method for the generation of multiple homogeneous field volumes inside the bore of superconducting magnets

PubMed Central

Chou, Ching-Yu; Ferrage, Fabien; Aubert, Guy; Sakellariou, Dimitris

2015-01-01

Standard Magnetic Resonance magnets produce a single homogeneous field volume, where the analysis is performed. Nonetheless, several modern applications could benefit from the generation of multiple homogeneous field volumes along the axis and inside the bore of the magnet. In this communication, we propose a straightforward method using a combination of ring structures of permanent magnets in order to cancel the gradient of the stray field in a series of distinct volumes. These concepts were demonstrated numerically on an experimentally measured magnetic field profile. We discuss advantages and limitations of our method and present the key steps required for an experimental validation. PMID:26182891

Abnormal resting-state connectivity of motor and cognitive networks in early manifest Huntington's disease.

PubMed

Wolf, R C; Sambataro, F; Vasic, N; Depping, M S; Thomann, P A; Landwehrmeyer, G B; Süssmuth, S D; Orth, M

2014-11-01

Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's 'resting state' could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients. Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and 'biological parametric mapping' analyses to investigate the impact of atrophy on neural activity. Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition. This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.

Genomic insights into the metabolic potential and interactions between marine methanotrophic ANME archaea and associated bacteria

NASA Astrophysics Data System (ADS)

Orphan, V. J.; Skennerton, C.; Chadwick, G.; Haroon, F.; Tyson, G. W.; Leu, A.; Hatzenpichler, R.; Woyke, T.; Malmstrom, R.; Yu, H.; Scheller, S.

2015-12-01

Cooperative metabolic interactions between multiple groups of methanotrophic 'ANME' archaea and sulfate-reducing bacteria represent the primary sink for methane within continental margin sediments. These syntrophic associations are frequently observed as structured multi-celled consortia in methane seeps, often comprising a substantial proportion of the microbial biomass within near seafloor seep sediments. Since their discovery nearly 15 years ago, a number of distinct ANME groups and multiple sulfate-reducing bacterial partners have been described from seep environments worldwide. Attempts to reconstruct the genomes of some ANME organisms have been reported, however the ecological physiology and metabolic interactions of distinct ANME lineages and their bacterial partners remains poorly understood. Here, we used a fluorescence azide-alkyne click chemistry technique known as BONCAT combined with FAC sorting to examine patterns in microbial membership and the genomes of single, metabolically active ANME-bacterial consortia recovered from methane seep sediments. This targeted consortia-level sequencing approach revealed significant diversity in the ANME-bacterial associations in situ as well as insights into the potential syntrophic mechanisms underpinning these enigmatic methane-fueled partnerships.

Multiple pore conformations driven by asynchronous movements of voltage sensors in a eukaryotic sodium channel

PubMed Central

Goldschen-Ohm, Marcel P.; Capes, Deborah L.; Oelstrom, Kevin M.; Chanda, Baron

2013-01-01

Voltage-dependent Na+ channels are crucial for electrical signalling in excitable cells. Membrane depolarization initiates asynchronous movements in four non-identical voltage-sensing domains of the Na+ channel. It remains unclear to what extent this structural asymmetry influences pore gating as compared with outwardly rectifying K+ channels, where channel opening results from a final concerted transition of symmetric pore gates. Here we combine single channel recordings, cysteine accessibility and voltage clamp fluorimetry to probe the relationships between voltage sensors and pore conformations in an inactivation deficient Nav1.4 channel. We observe three distinct conductance levels such that DI-III voltage sensor activation is kinetically correlated with formation of a fully open pore, whereas DIV voltage sensor movement underlies formation of a distinct subconducting pore conformation preceding inactivation in wild-type channels. Our experiments reveal that pore gating in sodium channels involves multiple transitions driven by asynchronous movements of voltage sensors. These findings shed new light on the mechanism of coupling between activation and fast inactivation in voltage-gated sodium channels. PMID:23322038

Architecture and High-Resolution Structure of Bacillus thuringiensis and Bacillus cereus Spore Coat Surfaces

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

Plomp, M; Leighton, T; Wheeler, K

2005-02-18

We have utilized atomic force microscopy (AFM) to visualize the native surface topology and ultrastructure of Bacillus thuringiensis and Bacillus cereus spores in water and in air. AFM was able to resolve the nanostructure of the exosporium and three distinctive classes of appendages. Removal of the exosporium exposed either a hexagonal honeycomb layer (B. thuringiensis) or a rodlet outer spore coat layer (B. cereus). Removal of the rodlet structure from B. cereus spores revealed an underlying honeycomb layer similar to that observed with B. thuringiensis spores. The periodicity of the rodlet structure on the outer spore coat of B. cereusmore » was {approx}8 nm, and the length of the rodlets was limited to the cross-patched domain structure of this layer to {approx}200 nm. The lattice constant of the honeycomb structures was {approx}9 nm for both B. cereus and B. thuringiensis spores. Both honeycomb structures were composed of multiple, disoriented domains with distinct boundaries. Our results demonstrate that variations in storage and preparation procedures result in architectural changes in individual spore surfaces, which establish AFM as a useful tool for evaluation of preparation and processing ''fingerprints'' of bacterial spores. These results establish that high-resolution AFM has the capacity to reveal species-specific assembly and nanometer scale structure of spore surfaces. These species-specific spore surface structural variations are correlated with sequence divergences in a spore core structural protein SspE.« less

Multiple regimes of robust patterns between network structure and biodiversity

NASA Astrophysics Data System (ADS)

Jover, Luis F.; Flores, Cesar O.; Cortez, Michael H.; Weitz, Joshua S.

2015-12-01

Ecological networks such as plant-pollinator and host-parasite networks have structured interactions that define who interacts with whom. The structure of interactions also shapes ecological and evolutionary dynamics. Yet, there is significant ongoing debate as to whether certain structures, e.g., nestedness, contribute positively, negatively or not at all to biodiversity. We contend that examining variation in life history traits is key to disentangling the potential relationship between network structure and biodiversity. Here, we do so by analyzing a dynamic model of virus-bacteria interactions across a spectrum of network structures. Consistent with prior studies, we find plausible parameter domains exhibiting strong, positive relationships between nestedness and biodiversity. Yet, the same model can exhibit negative relationships between nestedness and biodiversity when examined in a distinct, plausible region of parameter space. We discuss steps towards identifying when network structure could, on its own, drive the resilience, sustainability, and even conservation of ecological communities.

Multiple regimes of robust patterns between network structure and biodiversity

PubMed Central

Jover, Luis F.; Flores, Cesar O.; Cortez, Michael H.; Weitz, Joshua S.

2015-01-01

Ecological networks such as plant-pollinator and host-parasite networks have structured interactions that define who interacts with whom. The structure of interactions also shapes ecological and evolutionary dynamics. Yet, there is significant ongoing debate as to whether certain structures, e.g., nestedness, contribute positively, negatively or not at all to biodiversity. We contend that examining variation in life history traits is key to disentangling the potential relationship between network structure and biodiversity. Here, we do so by analyzing a dynamic model of virus-bacteria interactions across a spectrum of network structures. Consistent with prior studies, we find plausible parameter domains exhibiting strong, positive relationships between nestedness and biodiversity. Yet, the same model can exhibit negative relationships between nestedness and biodiversity when examined in a distinct, plausible region of parameter space. We discuss steps towards identifying when network structure could, on its own, drive the resilience, sustainability, and even conservation of ecological communities. PMID:26632996

Amoxicillin and Clavulanate Form Chemically and Immunologically Distinct Multiple Haptenic Structures in Patients.

PubMed

Meng, Xiaoli; Earnshaw, Caroline J; Tailor, Arun; Jenkins, Rosalind E; Waddington, James C; Whitaker, Paul; French, Neil S; Naisbitt, Dean J; Park, B Kevin

2016-10-17

Amoxicillin-clavulanate (AC) is one of the most common causes of drug induced liver injury (DILI). The association between AC-DILI and HLA alleles and the detection of drug-specific T cells in patients with AC-DILI indicate that the adaptive immune system is involved in the disease pathogenesis. In this study, mass spectrometric methods were employed to characterize the antigen formed by AC in exposed patients and the antigenic determinants that stimulate T cells. Amoxicillin formed penicilloyl adducts with lysine residues on human serum albumin (HSA) in vitro, with K190 and K199 being the most reactive sites. Amoxicillin-modified K190 and K199 have also been detected in all patients, and more extensive modification was observed in patients exposed to higher doses of amoxicillin. In contrast, the binding of clavulanic acid to HSA was more complicated. Multiple adducts were identified at high concentrations in vitro, including those formed by direct binding of clavulanic acid to lysine residues, novel pyrazine adducts derived from binding to the degradation products of clavulanic acid, and a cross-linking adduct. Stable adducts derived from formylacetic acid were detected in all patients exposed to the drug. Importantly, analysis of hapten-protein adducts formed in the cell culture medium revealed that the highly drug-specific T-cell responses were likely driven by the markedly different haptenic structures formed by these two drugs. In this study, the unique haptenic structures on albumin in patients formed by amoxicillin and clavulanic acid have been characterized and shown to function as chemically distinct antigens which can stimulate separate, specific T-cell clones.

A feature-based developmental model of the infant brain in structural MRI.

PubMed

Toews, Matthew; Wells, William M; Zöllei, Lilla

2012-01-01

In this paper, anatomical development is modeled as a collection of distinctive image patterns localized in space and time. A Bayesian posterior probability is defined over a random variable of subject age, conditioned on data in the form of scale-invariant image features. The model is automatically learned from a large set of images exhibiting significant variation, used to discover anatomical structure related to age and development, and fit to new images to predict age. The model is applied to a set of 230 infant structural MRIs of 92 subjects acquired at multiple sites over an age range of 8-590 days. Experiments demonstrate that the model can be used to identify age-related anatomical structure, and to predict the age of new subjects with an average error of 72 days.

Shapes, scents and sounds: quantifying the full multi-sensory basis of conceptual knowledge.

PubMed

Hoffman, Paul; Lambon Ralph, Matthew A

2013-01-01

Contemporary neuroscience theories assume that concepts are formed through experience in multiple sensory-motor modalities. Quantifying the contribution of each modality to different object categories is critical to understanding the structure of the conceptual system and to explaining category-specific knowledge deficits. Verbal feature listing is typically used to elicit this information but has a number of drawbacks: sensory knowledge often cannot easily be translated into verbal features and many features are experienced in multiple modalities. Here, we employed a more direct approach in which subjects rated their knowledge of objects in each sensory-motor modality separately. Compared with these ratings, feature listing over-estimated the importance of visual form and functional knowledge and under-estimated the contributions of other sensory channels. An item's sensory rating proved to be a better predictor of lexical-semantic processing speed than the number of features it possessed, suggesting that ratings better capture the overall quantity of sensory information associated with a concept. Finally, the richer, multi-modal rating data not only replicated the sensory-functional distinction between animals and non-living things but also revealed novel distinctions between different types of artefact. Hierarchical cluster analyses indicated that mechanical devices (e.g., vehicles) were distinct from other non-living objects because they had strong sound and motion characteristics, making them more similar to animals in this respect. Taken together, the ratings align with neuroscience evidence in suggesting that a number of distinct sensory processing channels make important contributions to object knowledge. Multi-modal ratings for 160 objects are provided as supplementary materials. Copyright © 2012 Elsevier Ltd. All rights reserved.

On the universal structure of human lexical semantics

PubMed Central

Sutton, Logan; Smith, Eric; Moore, Cristopher; Wilkins, Jon F.; Maddieson, Ian; Croft, William

2016-01-01

How universal is human conceptual structure? The way concepts are organized in the human brain may reflect distinct features of cultural, historical, and environmental background in addition to properties universal to human cognition. Semantics, or meaning expressed through language, provides indirect access to the underlying conceptual structure, but meaning is notoriously difficult to measure, let alone parameterize. Here, we provide an empirical measure of semantic proximity between concepts using cross-linguistic dictionaries to translate words to and from languages carefully selected to be representative of worldwide diversity. These translations reveal cases where a particular language uses a single “polysemous” word to express multiple concepts that another language represents using distinct words. We use the frequency of such polysemies linking two concepts as a measure of their semantic proximity and represent the pattern of these linkages by a weighted network. This network is highly structured: Certain concepts are far more prone to polysemy than others, and naturally interpretable clusters of closely related concepts emerge. Statistical analysis of the polysemies observed in a subset of the basic vocabulary shows that these structural properties are consistent across different language groups, and largely independent of geography, environment, and the presence or absence of a literary tradition. The methods developed here can be applied to any semantic domain to reveal the extent to which its conceptual structure is, similarly, a universal attribute of human cognition and language use. PMID:26831113

Raman and infrared spectroscopic study of the anhydrous carbonate minerals shortite and barytocalcite.

PubMed

Frost, Ray L; Dickfos, Marilla J

2008-11-01

The Raman spectra of shortite and barytocalcite complimented with infrared spectra have been used to characterise the structure of these carbonate minerals. The Raman spectrum of barytocalcite shows a single band at 1086 cm(-1) attributed to the (CO3)(2-) symmetric stretching mode, in contrast to shortite where two bands are observed. The observation of two bands for shortite confirms the concept of more than one crystallographically distinct carbonate unit in the unit cell. Multiple bands are observed for the antisymmetric stretching and bending region for these minerals proving that the carbonate unit is distorted in the structure of both shortite and barytocalcite.

Multitask TSK fuzzy system modeling by mining intertask common hidden structure.

PubMed

Jiang, Yizhang; Chung, Fu-Lai; Ishibuchi, Hisao; Deng, Zhaohong; Wang, Shitong

2015-03-01

The classical fuzzy system modeling methods implicitly assume data generated from a single task, which is essentially not in accordance with many practical scenarios where data can be acquired from the perspective of multiple tasks. Although one can build an individual fuzzy system model for each task, the result indeed tells us that the individual modeling approach will get poor generalization ability due to ignoring the intertask hidden correlation. In order to circumvent this shortcoming, we consider a general framework for preserving the independent information among different tasks and mining hidden correlation information among all tasks in multitask fuzzy modeling. In this framework, a low-dimensional subspace (structure) is assumed to be shared among all tasks and hence be the hidden correlation information among all tasks. Under this framework, a multitask Takagi-Sugeno-Kang (TSK) fuzzy system model called MTCS-TSK-FS (TSK-FS for multiple tasks with common hidden structure), based on the classical L2-norm TSK fuzzy system, is proposed in this paper. The proposed model can not only take advantage of independent sample information from the original space for each task, but also effectively use the intertask common hidden structure among multiple tasks to enhance the generalization performance of the built fuzzy systems. Experiments on synthetic and real-world datasets demonstrate the applicability and distinctive performance of the proposed multitask fuzzy system model in multitask regression learning scenarios.

Morphological, structural, and spectral characteristics of amorphous iron sulfates

PubMed Central

Sklute, E. C.; Jensen, H. B.; Rogers, A. D.; Reeder, R. J.

2018-01-01

Current or past brine hydrologic activity on Mars may provide suitable conditions for the formation of amorphous ferric sulfates. Once formed, these phases would likely be stable under current Martian conditions, particularly at low- to mid-latitudes. Therefore, we consider amorphous iron sulfates (AIS) as possible components of Martian surface materials. Laboratory AIS were created through multiple synthesis routes and characterized with total X-ray scattering, thermogravimetric analysis, scanning electron microscopy, visible/near-infrared (VNIR), thermal infrared (TIR), and Mössbauer techniques. We synthesized amorphous ferric sulfates (Fe(III)2(SO4)3 · ~ 6–8H2O) from sulfate-saturated fluids via vacuum dehydration or exposure to low relative humidity (<11%). Amorphous ferrous sulfate (Fe(II)SO4 · ~1H2O) was synthesized via vacuum dehydration of melanterite. All AIS lack structural order beyond 11 Å. The short-range (<5 Å) structural characteristics of amorphous ferric sulfates resemble all crystalline reference compounds; structural characteristics for the amorphous ferrous sulfate are similar to but distinct from both rozenite and szomolnokite. VNIR and TIR spectral data for all AIS display broad, muted features consistent with structural disorder and are spectrally distinct from all crystalline sulfates considered for comparison. Mössbauer spectra are also distinct from crystalline phase spectra available for comparison. AIS should be distinguishable from crystalline sulfates based on the position of their Fe-related absorptions in the visible range and their spectral characteristics in the TIR. In the NIR, bands associated with hydration at ~1.4 and 1.9 μm are significantly broadened, which greatly reduces their detectability in soil mixtures. AIS may contribute to the amorphous fraction of soils measured by the Curiosity rover. PMID:29675340

Microfocus diffraction from different regions of a protein crystal: structural variations and unit-cell polymorphism

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

Thompson, Michael C.; Cascio, Duilio; Yeates, Todd O.

Real macromolecular crystals can be non-ideal in a myriad of ways. This often creates challenges for structure determination, while also offering opportunities for greater insight into the crystalline state and the dynamic behavior of macromolecules. To evaluate whether different parts of a single crystal of a dynamic protein, EutL, might be informative about crystal and protein polymorphism, a microfocus X-ray synchrotron beam was used to collect a series of 18 separate data sets from non-overlapping regions of the same crystal specimen. A principal component analysis (PCA) approach was employed to compare the structure factors and unit cells across the datamore » sets, and it was found that the 18 data sets separated into two distinct groups, with largeRvalues (in the 40% range) and significant unit-cell variations between the members of the two groups. This categorization mapped the different data-set types to distinct regions of the crystal specimen. Atomic models of EutL were then refined against two different data sets obtained by separately merging data from the two distinct groups. A comparison of the two resulting models revealed minor but discernable differences in certain segments of the protein structure, and regions of higher deviation were found to correlate with regions where larger dynamic motions were predicted to occur by normal-mode molecular-dynamics simulations. The findings emphasize that large spatially dependent variations may be present across individual macromolecular crystals. This information can be uncovered by simultaneous analysis of multiple partial data sets and can be exploited to reveal new insights about protein dynamics, while also improving the accuracy of the structure-factor data ultimately obtained in X-ray diffraction experiments.« less

The Rock Elm meteorite impact structure, Wisconsin: Geology and shock-metamorphic effects in quartz

USGS Publications Warehouse

French, B.M.; Cordua, W.S.; Plescia, J.B.

2004-01-01

The Rock Elm structure in southwest Wisconsin is an anomalous circular area of highly deformed rocks, ???6.5 km in diameter, located in a region of virtually horizontal undeformed sedimentary rocks. Shock-produced planar microstructures (PMs) have been identified in quartz grains in several lithologies associated with the structure: sandstones, quartzite pebbles, and breccia. Two distinct types of PMs are present: P1 features, which appear identical to planar fractures (PFs or cleavage), and P2 features, which are interpreted as possible incipient planar deformation features (PDFs). The latter are uniquely produced by the shock waves associated with meteorite impact events. Both types of PMs are oriented parallel to specific crystallographic planes in the quartz, most commonly to c(0001), ??112??2, and r/z101??1. The association of unusual, structurally deformed strata with distinct shock-produced microdeformation features in their quartz-bearing rocks establishes Rock Elm as a meteorite impact structure and supports the view that the presence of multiple parallel cleavages in quartz may be used independently as a criterion for meteorite impact. Preliminary paleontological studies indicate a minimum age of Middle Ordovician for the Rock Elm structure. A similar age estimate (450-400 Ma) is obtained independently by combining the results of studies of the general morphology of complex impact structures with estimated rates of sedimentation for the region. Such methods may be applicable to dating other old and deeply eroded impact structures formed in sedimentary target rocks.

Reusable EGaIn-Injected Substrate-Integrated-Waveguide Resonator for Wireless Sensor Applications

PubMed Central

Memon, Muhammad Usman; Lim, Sungjoon

2015-01-01

The proposed structure in this research is constructed on substrate integrated waveguide (SIW) technology and has a mechanism that produces 16 different and distinct resonant frequencies between 2.45 and 3.05 GHz by perturbing a fundamental TE10 mode. It is a unique method for producing multiple resonances in a radio frequency planar structure without any extra circuitry or passive elements is developed. The proposed SIW structure has four vertical fluidic holes (channels); injecting eutectic gallium indium (EGaIn), also known commonly as liquid metal (LM), into these vertical channels produces different resonant frequencies. Either a channel is empty, or it is filled with LM. In total, the combination of different frequencies produced from four vertical channels is 16. PMID:26569257

The same pocket in menin binds both MLL and JUND but has opposite effects on transcription

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

Huang, Jing; Gurung, Buddha; Wan, Bingbing

2013-04-08

Menin is a tumour suppressor protein whose loss or inactivation causes multiple endocrine neoplasia 1 (MEN1), a hereditary autosomal dominant tumour syndrome that is characterized by tumorigenesis in multiple endocrine organs. Menin interacts with many proteins and is involved in a variety of cellular processes. Menin binds the JUN family transcription factor JUND and inhibits its transcriptional activity. Several MEN1 missense mutations disrupt the menin-JUND interaction, suggesting a correlation between the tumour-suppressor function of menin and its suppression of JUND-activated transcription. Menin also interacts with mixed lineage leukaemia protein 1 (MLL1), a histone H3 lysine 4 methyltransferase, and functions asmore » an oncogenic cofactor to upregulate gene transcription and promote MLL1-fusion-protein-induced leukaemogenesis. A recent report on the tethering of MLL1 to chromatin binding factor lens epithelium-derived growth factor (LEDGF) by menin indicates that menin is a molecular adaptor coordinating the functions of multiple proteins. Despite its importance, how menin interacts with many distinct partners and regulates their functions remains poorly understood. Here we present the crystal structures of human menin in its free form and in complexes with MLL1 or with JUND, or with an MLL1-LEDGF heterodimer. These structures show that menin contains a deep pocket that binds short peptides of MLL1 or JUND in the same manner, but that it can have opposite effects on transcription. The menin-JUND interaction blocks JUN N-terminal kinase (JNK)-mediated JUND phosphorylation and suppresses JUND-induced transcription. In contrast, menin promotes gene transcription by binding the transcription activator MLL1 through the peptide pocket while still interacting with the chromatin-anchoring protein LEDGF at a distinct surface formed by both menin and MLL1.« less

Transposition of foliations and superposition of lineations during polyphase deformation in the Nevado-Filabride complex: tectonic implications

NASA Astrophysics Data System (ADS)

Ruiz-Fuentes, Alejandro; Aerden, Domingo G. A. M.

2018-01-01

Detailed structural analysis in a ca. 80 km2 area of the western Nevado-Filabride complex (Betic Cordillera) reveals a heterogeneous internal structure characterized by multiple cross-cutting foliations and lineations that locally transpose earlier ones. The large-scale geometry of these fabrics conflicts with continuous westward to south-westward tectonic transport related to thrusting or crustal extension, and mismatches a previously inferred extensional detachment in the area. Multiple crenulation lineations can be distinguished in the field and correlated with five foliation intersection axes (FIA1-5) preserved in garnet and plagioclase porphyroblasts of the western Sierra Nevada. These indicate crustal shortening in different directions associated with vertical foliation development and intermitted stages of gravitational collapse producing horizontal foliations. The large spread of lineation- and fold-axes trends in the Nevado-Filabride complex results from the mixed presence of multiple generations of these structures whose distinction is critical for tectonic models. The five principal FIA trends remarkably match successive vectors of relative Africa-Iberia plate motion since the Eocene, suggesting that deformation of the Nevado-Filabride took place during this period, although peak metamorphism in at least some of its parts was reached as late as the Middle Miocene.

Morphological and ontogenetic stratification of abyssal and hadal Eurythenes gryllus sensu lato (Amphipoda: Lysianassoidea) from the Peru-Chile Trench

NASA Astrophysics Data System (ADS)

Eustace, Ryan M.; Ritchie, Heather; Kilgallen, Niamh M.; Piertney, Stuart B.; Jamieson, Alan J.

2016-03-01

The globally ubiquitous lysianassoid amphipod, Eurythenes gryllus, has been shown to consist of multiple genetically distinct cryptic taxa, with depth considered a major driver of speciation and morphological divergence. Here we examine morphological variation of E. gryllus sensu lato through a continuous depth distribution that spans from abyssal (3000-6000 m) into hadal depths (>6000 m) in the Peru-Chile Trench (SE Pacific Ocean). Three distinct morphospecies were identified: one was confirmed as being E. magellanicus (4602-5329 m) based on DNA sequence and morphological similarity. The other two morphologically distinct species were named based upon depth of occurrence; Abyssal (4602-6173 m) and Hadal (6173-8074 m). The three Eurythenes morphospecies showed vertical ontogenetic stratification across their bathymetric range, where juveniles were found shallower in their depth range and mature females deeper. Potential ecological and evolutionary drivers that explain the observed patterns of intra and inter-specific structure, such as hydrostatic pressure and topographical isolation, are discussed.

A review of current evidence regarding the ICD-11 proposals for diagnosing PTSD and complex PTSD.

PubMed

Brewin, Chris R; Cloitre, Marylène; Hyland, Philip; Shevlin, Mark; Maercker, Andreas; Bryant, Richard A; Humayun, Asma; Jones, Lynne M; Kagee, Ashraf; Rousseau, Cécile; Somasundaram, Daya; Suzuki, Yuriko; Wessely, Simon; van Ommeren, Mark; Reed, Geoffrey M

2017-12-01

The World Health Organization's proposals for posttraumatic stress disorder (PTSD) in the 11th edition of the International Classification of Diseases, scheduled for release in 2018, involve a very brief set of symptoms and a distinction between two sibling disorders, PTSD and Complex PTSD. This review of studies conducted to test the validity and implications of the diagnostic proposals generally supports the proposed 3-factor structure of PTSD symptoms, the 6-factor structure of Complex PTSD symptoms, and the distinction between PTSD and Complex PTSD. Estimates derived from DSM-based items suggest the likely prevalence of ICD-11 PTSD in adults is lower than ICD-10 PTSD and lower than DSM-IV or DSM-5 PTSD, but this may change with the development of items that directly measure the ICD-11 re-experiencing requirement. Preliminary evidence suggests the prevalence of ICD-11 PTSD in community samples of children and adolescents is similar to DSM-IV and DSM-5. ICD-11 PTSD detects some individuals with significant impairment who would not receive a diagnosis under DSM-IV or DSM-5. ICD-11 CPTSD identifies a distinct group who have more often experienced multiple and sustained traumas and have greater functional impairment than those with PTSD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Defined types of cortical interneurone structure space and spike timing in the hippocampus

PubMed Central

Somogyi, Peter; Klausberger, Thomas

2005-01-01

The cerebral cortex encodes, stores and combines information about the internal and external environment in rhythmic activity of multiple frequency ranges. Neurones of the cortex can be defined, recognized and compared on the comprehensive application of the following measures: (i) brain area- and cell domain-specific distribution of input and output synapses, (ii) expression of molecules involved in cell signalling, (iii) membrane and synaptic properties reflecting the expression of membrane proteins, (iv) temporal structure of firing in vivo, resulting from (i)–(iii). Spatial and temporal measures of neurones in the network reflect an indivisible unity of evolutionary design, i.e. neurones do not have separate structure or function. The blueprint of this design is most easily accessible in the CA1 area of the hippocampus, where a relatively uniform population of pyramidal cells and their inputs follow an instantly recognizable laminated pattern and act within stereotyped network activity patterns. Reviewing the cell types and their spatio-temporal interactions, we suggest that CA1 pyramidal cells are supported by at least 16 distinct types of GABAergic neurone. During a given behaviour-contingent network oscillation, interneurones of a given type exhibit similar firing patterns. During different network oscillations representing two distinct brain states, interneurones of the same class show different firing patterns modulating their postsynaptic target-domain in a brain-state-dependent manner. These results suggest roles for specific interneurone types in structuring the activity of pyramidal cells via their respective target domains, and accurately timing and synchronizing pyramidal cell discharge, rather than providing generalized inhibition. Finally, interneurones belonging to different classes may fire preferentially at distinct time points during a given oscillation. As different interneurones innervate distinct domains of the pyramidal cells, the different compartments will receive GABAergic input differentiated in time. Such a dynamic, spatio-temporal, GABAergic control, which evolves distinct patterns during different brain states, is ideally suited to regulating the input integration of individual pyramidal cells contributing to the formation of cell assemblies and representations in the hippocampus and, probably, throughout the cerebral cortex. PMID:15539390

Amino acid sequence analysis of the annexin super-gene family of proteins.

PubMed

Barton, G J; Newman, R H; Freemont, P S; Crumpton, M J

1991-06-15

The annexins are a widespread family of calcium-dependent membrane-binding proteins. No common function has been identified for the family and, until recently, no crystallographic data existed for an annexin. In this paper we draw together 22 available annexin sequences consisting of 88 similar repeat units, and apply the techniques of multiple sequence alignment, pattern matching, secondary structure prediction and conservation analysis to the characterisation of the molecules. The analysis clearly shows that the repeats cluster into four distinct families and that greatest variation occurs within the repeat 3 units. Multiple alignment of the 88 repeats shows amino acids with conserved physicochemical properties at 22 positions, with only Gly at position 23 being absolutely conserved in all repeats. Secondary structure prediction techniques identify five conserved helices in each repeat unit and patterns of conserved hydrophobic amino acids are consistent with one face of a helix packing against the protein core in predicted helices a, c, d, e. Helix b is generally hydrophobic in all repeats, but contains a striking pattern of repeat-specific residue conservation at position 31, with Arg in repeats 4 and Glu in repeats 2, but unconserved amino acids in repeats 1 and 3. This suggests repeats 2 and 4 may interact via a buried saltbridge. The loop between predicted helices a and b of repeat 3 shows features distinct from the equivalent loop in repeats 1, 2 and 4, suggesting an important structural and/or functional role for this region. No compelling evidence emerges from this study for uteroglobin and the annexins sharing similar tertiary structures, or for uteroglobin representing a derivative of a primordial one-repeat structure that underwent duplication to give the present day annexins. The analyses performed in this paper are re-evaluated in the Appendix, in the light of the recently published X-ray structure for human annexin V. The structure confirms most of the predictions and shows the power of techniques for the determination of tertiary structural information from the amino acid sequences of an aligned protein family.

An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues.

PubMed

Corces, M Ryan; Trevino, Alexandro E; Hamilton, Emily G; Greenside, Peyton G; Sinnott-Armstrong, Nicholas A; Vesuna, Sam; Satpathy, Ansuman T; Rubin, Adam J; Montine, Kathleen S; Wu, Beijing; Kathiria, Arwa; Cho, Seung Woo; Mumbach, Maxwell R; Carter, Ava C; Kasowski, Maya; Orloff, Lisa A; Risca, Viviana I; Kundaje, Anshul; Khavari, Paul A; Montine, Thomas J; Greenleaf, William J; Chang, Howard Y

2017-10-01

We present Omni-ATAC, an improved ATAC-seq protocol for chromatin accessibility profiling that works across multiple applications with substantial improvement of signal-to-background ratio and information content. The Omni-ATAC protocol generates chromatin accessibility profiles from archival frozen tissue samples and 50-μm sections, revealing the activities of disease-associated DNA elements in distinct human brain structures. The Omni-ATAC protocol enables the interrogation of personal regulomes in tissue context and translational studies.

Multiple chiral topological states in liquid crystals from unstructured light beams

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

Loussert, Charles; Brasselet, Etienne, E-mail: e.brasselet@loma.u-bordeaux1.fr

2014-02-03

It is shown experimentally that unstructured light beams can generate a wealth of distinct metastable defect structures in thin films of chiral liquid crystals. Various kinds of individual chiral topological states are obtained as well as dimers and trimers, which correspond to the entanglement of several topological unit cells. Self-assembled nested assemblies of several metastable particle-like topological states can also be formed. Finally, we propose and experimentally demonstrate an opto-electrical approach to generate tailor-made architectures.

Age-related differences in the structural complexity of subcortical and ventricular structures.

PubMed

Madan, Christopher R; Kensinger, Elizabeth A

2017-02-01

It has been well established that the volume of several subcortical structures decreases in relation to age. Different metrics of cortical structure (e.g., volume, thickness, surface area, and gyrification) have been shown to index distinct characteristics of interindividual differences; thus, it is important to consider the relation of age to multiple structural measures. Here, we compare age-related differences in subcortical and ventricular volume to those differences revealed with a measure of structural complexity, quantified as fractal dimensionality. Across 3 large data sets, totaling nearly 900 individuals across the adult lifespan (aged 18-94 years), we found greater age-related differences in complexity than volume for the subcortical structures, particularly in the caudate and thalamus. The structural complexity of ventricular structures was not more strongly related to age than volume. These results demonstrate that considering shape-related characteristics improves sensitivity to detect age-related differences in subcortical structures. Copyright © 2016 Elsevier Inc. All rights reserved.

Structural basis for specific recognition of multiple mRNA targets by a PUF regulatory protein

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

Wang, Yeming; Opperman, Laura; Wickens, Marvin

2011-11-02

Caenorhabditis elegans fem-3 binding factor (FBF) is a founding member of the PUMILIO/FBF (PUF) family of mRNA regulatory proteins. It regulates multiple mRNAs critical for stem cell maintenance and germline development. Here, we report crystal structures of FBF in complex with 6 different 9-nt RNA sequences, including elements from 4 natural mRNAs. These structures reveal that FBF binds to conserved bases at positions 1-3 and 7-8. The key specificity determinant of FBF vs. other PUF proteins lies in positions 4-6. In FBF/RNA complexes, these bases stack directly with one another and turn away from the RNA-binding surface. A short regionmore » of FBF is sufficient to impart its unique specificity and lies directly opposite the flipped bases. We suggest that this region imposes a flattened curvature on the protein; hence, the requirement for the additional nucleotide. The principles of FBF/RNA recognition suggest a general mechanism by which PUF proteins recognize distinct families of RNAs yet exploit very nearly identical atomic contacts in doing so.« less

Structural basis for specific recognition of multiple mRNA targets by a PUF regulatory protein

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

Wang, Yeming; Opperman, Laura; Wickens, Marvin

2010-08-19

Caenorhabditis elegans fem-3 binding factor (FBF) is a founding member of the PUMILIO/FBF (PUF) family of mRNA regulatory proteins. It regulates multiple mRNAs critical for stem cell maintenance and germline development. Here, we report crystal structures of FBF in complex with 6 different 9-nt RNA sequences, including elements from 4 natural mRNAs. These structures reveal that FBF binds to conserved bases at positions 1-3 and 7-8. The key specificity determinant of FBF vs. other PUF proteins lies in positions 4-6. In FBF/RNA complexes, these bases stack directly with one another and turn away from the RNA-binding surface. A short regionmore » of FBF is sufficient to impart its unique specificity and lies directly opposite the flipped bases. We suggest that this region imposes a flattened curvature on the protein; hence, the requirement for the additional nucleotide. The principles of FBF/RNA recognition suggest a general mechanism by which PUF proteins recognize distinct families of RNAs yet exploit very nearly identical atomic contacts in doing so.« less

Characterization of cell surface and extracellular matrix remodeling of Azospirillum brasilense chemotaxis-like 1 signal transduction pathway mutants by atomic force microscopy.

PubMed

Edwards, Amanda Nicole; Siuti, Piro; Bible, Amber N; Alexandre, Gladys; Retterer, Scott T; Doktycz, Mitchel J; Morrell-Falvey, Jennifer L

2011-01-01

To compete in complex microbial communities, bacteria must sense environmental changes and adjust cellular functions for optimal growth. Chemotaxis-like signal transduction pathways are implicated in the regulation of multiple behaviors in response to changes in the environment, including motility patterns, exopolysaccharide production, and cell-to-cell interactions. In Azospirillum brasilense, cell surface properties, including exopolysaccharide production, are thought to play a direct role in promoting flocculation. Recently, the Che1 chemotaxis-like pathway from A. brasilense was shown to modulate flocculation, suggesting an associated modulation of cell surface properties. Using atomic force microscopy, distinct changes in the surface morphology of flocculating A. brasilense Che1 mutant strains were detected. Whereas the wild-type strain produces a smooth mucosal extracellular matrix after 24 h, the flocculating Che1 mutant strains produce distinctive extracellular fibril structures. Further analyses using flocculation inhibition, lectin-binding assays, and comparison of lipopolysaccharides profiles suggest that the extracellular matrix differs between the cheA1 and the cheY1 mutants, despite an apparent similarity in the macroscopic floc structures. Collectively, these data indicate that disruption of the Che1 pathway is correlated with distinctive changes in the extracellular matrix, which likely result from changes in surface polysaccharides structure and/or composition. FEMS Microbiology Letters © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. No claim to original US government works.

Cellulose synthase complexes act in a concerted fashion to synthesize highly aggregated cellulose in secondary cell walls of plants

PubMed Central

Li, Shundai; Bashline, Logan; Zheng, Yunzhen; Xin, Xiaoran; Huang, Shixin; Kong, Zhaosheng; Kim, Seong H.; Cosgrove, Daniel J.; Gu, Ying

2016-01-01

Cellulose, often touted as the most abundant biopolymer on Earth, is a critical component of the plant cell wall and is synthesized by plasma membrane-spanning cellulose synthase (CESA) enzymes, which in plants are organized into rosette-like CESA complexes (CSCs). Plants construct two types of cell walls, primary cell walls (PCWs) and secondary cell walls (SCWs), which differ in composition, structure, and purpose. Cellulose in PCWs and SCWs is chemically identical but has different physical characteristics. During PCW synthesis, multiple dispersed CSCs move along a shared linear track in opposing directions while synthesizing cellulose microfibrils with low aggregation. In contrast, during SCW synthesis, we observed swaths of densely arranged CSCs that moved in the same direction along tracks while synthesizing cellulose microfibrils that became highly aggregated. Our data support a model in which distinct spatiotemporal features of active CSCs during PCW and SCW synthesis contribute to the formation of cellulose with distinct structure and organization in PCWs and SCWs of Arabidopsis thaliana. This study provides a foundation for understanding differences in the formation, structure, and organization of cellulose in PCWs and SCWs. PMID:27647923

Cellulose synthase complexes act in a concerted fashion to synthesize highly aggregated cellulose in secondary cell walls of plants.

PubMed

Li, Shundai; Bashline, Logan; Zheng, Yunzhen; Xin, Xiaoran; Huang, Shixin; Kong, Zhaosheng; Kim, Seong H; Cosgrove, Daniel J; Gu, Ying

2016-10-04

Cellulose, often touted as the most abundant biopolymer on Earth, is a critical component of the plant cell wall and is synthesized by plasma membrane-spanning cellulose synthase (CESA) enzymes, which in plants are organized into rosette-like CESA complexes (CSCs). Plants construct two types of cell walls, primary cell walls (PCWs) and secondary cell walls (SCWs), which differ in composition, structure, and purpose. Cellulose in PCWs and SCWs is chemically identical but has different physical characteristics. During PCW synthesis, multiple dispersed CSCs move along a shared linear track in opposing directions while synthesizing cellulose microfibrils with low aggregation. In contrast, during SCW synthesis, we observed swaths of densely arranged CSCs that moved in the same direction along tracks while synthesizing cellulose microfibrils that became highly aggregated. Our data support a model in which distinct spatiotemporal features of active CSCs during PCW and SCW synthesis contribute to the formation of cellulose with distinct structure and organization in PCWs and SCWs of Arabidopsis thaliana This study provides a foundation for understanding differences in the formation, structure, and organization of cellulose in PCWs and SCWs.

Process signatures in glatiramer acetate synthesis: structural and functional relationships.

PubMed

Campos-García, Víctor R; Herrera-Fernández, Daniel; Espinosa-de la Garza, Carlos E; González, German; Vallejo-Castillo, Luis; Avila, Sandra; Muñoz-García, Leslie; Medina-Rivero, Emilio; Pérez, Néstor O; Gracia-Mora, Isabel; Pérez-Tapia, Sonia Mayra; Salazar-Ceballos, Rodolfo; Pavón, Lenin; Flores-Ortiz, Luis F

2017-09-21

Glatiramer Acetate (GA) is an immunomodulatory medicine approved for the treatment of multiple sclerosis, whose mechanisms of action are yet to be fully elucidated. GA is comprised of a complex mixture of polypeptides with different amino acid sequences and structures. The lack of sensible information about physicochemical characteristics of GA has contributed to its comprehensiveness complexity. Consequently, an unambiguous determination of distinctive attributes that define GA is of highest relevance towards dissecting its identity. Herein we conducted a study of characteristic GA heterogeneities throughout its manufacturing process (process signatures), revealing a strong impact of critical process parameters (CPPs) on the reactivity of amino acid precursors; reaction initiation and polymerization velocities; and peptide solubility, susceptibility to hydrolysis, and size-exclusion properties. Further, distinctive GA heterogeneities were correlated to defined immunological and toxicological profiles, revealing that GA possesses a unique repertoire of active constituents (epitopes) responsible of its immunological responses, whose modification lead to altered profiles. This novel approach established CPPs influence on intact GA peptide mixture, whose physicochemical identity cannot longer rely on reduced properties (based on complete or partial GA degradation), providing advanced knowledge on GA structural and functional relationships to ensure a consistent manufacturing of safe and effective products.

Proteomics of Dense Core Secretory Vesicles Reveal Distinct Protein Categories for Secretion of Neuroeffectors for Cell-Cell Communication

PubMed Central

Wegrzyn, Jill L.; Bark, Steven J.; Funkelstein, Lydiane; Mosier, Charles; Yap, Angel; Kazemi-Esfarjani, Parasa; La Spada, Albert; Sigurdson, Christina; O’Connor, Daniel T.; Hook, Vivian

2010-01-01

Regulated secretion of neurotransmitters and neurohumoural factors from dense core secretory vesicles provides essential neuroeffectors for cell-cell communication in the nervous and endocrine systems. This study provides comprehensive proteomic characterization of the categories of proteins in chromaffin dense core secretory vesicles that participate in cell-cell communication from the adrenal medulla. Proteomic studies were conducted by nano-HPLC Chip MS/MS tandem mass spectrometry. Results demonstrate that these secretory vesicles contain proteins of distinct functional categories consisting of neuropeptides and neurohumoural factors, protease systems, neurotransmitter enzymes and transporters, receptors, enzymes for biochemical processes, reduction/oxidation regulation, ATPases, protein folding, lipid biochemistry, signal transduction, exocytosis, calcium regulation, as well as structural and cell adhesion proteins. The secretory vesicle proteomic data identified 371 distinct proteins in the soluble fraction and 384 distinct membrane proteins, for a total of 686 distinct secretory vesicle proteins. Notably, these proteomic analyses illustrate the presence of several neurological disease-related proteins in these secretory vesicles, including huntingtin interacting protein, cystatin C, ataxin 7, and prion protein. Overall, these findings demonstrate that multiple protein categories participate in dense core secretory vesicles for production, storage, and secretion of bioactive neuroeffectors for cell-cell communication in health and disease. PMID:20695487

Sequential Superresolution Imaging of Multiple Targets Using a Single Fluorophore

PubMed Central

Lidke, Diane S.; Lidke, Keith A.

2015-01-01

Fluorescence superresolution (SR) microscopy, or fluorescence nanoscopy, provides nanometer scale detail of cellular structures and allows for imaging of biological processes at the molecular level. Specific SR imaging methods, such as localization-based imaging, rely on stochastic transitions between on (fluorescent) and off (dark) states of fluorophores. Imaging multiple cellular structures using multi-color imaging is complicated and limited by the differing properties of various organic dyes including their fluorescent state duty cycle, photons per switching event, number of fluorescent cycles before irreversible photobleaching, and overall sensitivity to buffer conditions. In addition, multiple color imaging requires consideration of multiple optical paths or chromatic aberration that can lead to differential aberrations that are important at the nanometer scale. Here, we report a method for sequential labeling and imaging that allows for SR imaging of multiple targets using a single fluorophore with negligible cross-talk between images. Using brightfield image correlation to register and overlay multiple image acquisitions with ~10 nm overlay precision in the x-y imaging plane, we have exploited the optimal properties of AlexaFluor647 for dSTORM to image four distinct cellular proteins. We also visualize the changes in co-localization of the epidermal growth factor (EGF) receptor and clathrin upon EGF addition that are consistent with clathrin-mediated endocytosis. These results are the first to demonstrate sequential SR (s-SR) imaging using direct stochastic reconstruction microscopy (dSTORM), and this method for sequential imaging can be applied to any superresolution technique. PMID:25860558

Versatile protein recognition by the encoded display of multiple chemical elements on a constant macrocyclic scaffold

NASA Astrophysics Data System (ADS)

Li, Yizhou; De Luca, Roberto; Cazzamalli, Samuele; Pretto, Francesca; Bajic, Davor; Scheuermann, Jörg; Neri, Dario

2018-03-01

In nature, specific antibodies can be generated as a result of an adaptive selection and expansion of lymphocytes with suitable protein binding properties. We attempted to mimic antibody-antigen recognition by displaying multiple chemical diversity elements on a defined macrocyclic scaffold. Encoding of the displayed combinations was achieved using distinctive DNA tags, resulting in a library size of 35,393,112. Specific binders could be isolated against a variety of proteins, including carbonic anhydrase IX, horseradish peroxidase, tankyrase 1, human serum albumin, alpha-1 acid glycoprotein, calmodulin, prostate-specific antigen and tumour necrosis factor. Similar to antibodies, the encoded display of multiple chemical elements on a constant scaffold enabled practical applications, such as fluorescence microscopy procedures or the selective in vivo delivery of payloads to tumours. Furthermore, the versatile structure of the scaffold facilitated the generation of protein-specific chemical probes, as illustrated by photo-crosslinking.

Distinct pattern of lesion distribution in multiple sclerosis is associated with different circulating T-helper and helper-like innate lymphoid cell subsets.

PubMed

Gross, Catharina C; Schulte-Mecklenbeck, Andreas; Hanning, Uta; Posevitz-Fejfár, Anita; Korsukewitz, Catharina; Schwab, Nicholas; Meuth, Sven G; Wiendl, Heinz; Klotz, Luisa

2017-06-01

Distinct lesion topography in relapsing-remitting multiple sclerosis (RRMS) might be due to different antigen presentation and/or trafficking routes of immune cells into the central nervous system (CNS). To investigate whether distinct lesion patterns in multiple sclerosis (MS) might be associated with a predominance of distinct circulating T-helper cell subset as well as their innate counterparts. Flow cytometric analysis of lymphocytes derived from the peripheral blood of patients with exclusively cerebral (n = 20) or predominantly spinal (n = 12) disease manifestation. Patients with exclusively cerebral or preferential spinal lesion manifestation were associated with increased proportions of circulating granulocyte-macrophage colony-stimulating factor (GM-CSF) producing T H 1 cells or interleukin (IL)-17-producing T H 17 cells, respectively. In contrast, proportions of peripheral IL-17/IL-22-producing lymphoid tissue inducer (LTi), the innate counterpart of T H 17 cells, were enhanced in RRMS patients with exclusively cerebral lesion topography. Distinct T-helper and T-helper-like innate lymphoid cell (ILC) subsets are associated with different lesion topography in RRMS.

A Feature-based Developmental Model of the Infant Brain in Structural MRI

PubMed Central

Toews, Matthew; Wells, William M.; Zöllei, Lilla

2014-01-01

In this paper, anatomical development is modeled as a collection of distinctive image patterns localized in space and time. A Bayesian posterior probability is defined over a random variable of subject age, conditioned on data in the form of scale-invariant image features. The model is automatically learned from a large set of images exhibiting significant variation, used to discover anatomical structure related to age and development, and fit to new images to predict age. The model is applied to a set of 230 infant structural MRIs of 92 subjects acquired at multiple sites over an age range of 8-590 days. Experiments demonstrate that the model can be used to identify age-related anatomical structure, and to predict the age of new subjects with an average error of 72 days. PMID:23286050

Emerging structural insights into the function of ionotropic glutamate receptors

PubMed Central

Karakas, Erkan; Regan, Michael C.; Furukawa, Hiro

2015-01-01

Summary Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate excitatory neurotransmission crucial for brain development and function including learning and memory formation. Recently a wealth of structural studies on iGluRs, including AMPA receptors (AMPARs), kainate receptors, and NMDA receptors (NMDARs) became available.. These studies showed structures of non-NMDARs including AMPAR and kainate receptor in various functional states, thereby providing the first visual sense of how non-NMDAR iGluRs may function in the context of homotetramers. Furthermore, they provided the first view of heterotetrameric NMDAR ion channels, which illuminated the similarities with and differences from non-NMDARs, thus raising a mechanistic distinction between the two groups of iGluRs. Here we review mechanistic insights into iGluR functions gained through structural studies of multiple groups. PMID:25941168

The impact of aging on epithelial barriers.

PubMed

Parrish, Alan R

2017-10-02

The epithelium has many critical roles in homeostasis, including an essential responsibility in establishing tissue barriers. In addition to the fundamental role in separating internal from external environment, epithelial barriers maintain nutrient, fluid, electrolyte and metabolic waste balance in multiple organs. While, by definition, barrier function is conserved, the structure of the epithelium varies across organs. For example, the skin barrier is a squamous layer of cells with distinct structural features, while the lung barrier is composed of a very thin single cell to minimize diffusion space. With the increased focus on age-dependent alterations in organ structure and function, there is an emerging interest in the impact of age on epithelial barriers. This review will focus on the impact of aging on the epithelial barrier of several organs, including the skin, lung, gastrointestinal tract and the kidney, at a structural and functional level.

3D-printing and mechanics of bio-inspired articulated and multi-material structures.

PubMed

Porter, Michael M; Ravikumar, Nakul; Barthelat, Francois; Martini, Roberto

2017-09-01

3D-printing technologies allow researchers to build simplified physical models of complex biological systems to more easily investigate their mechanics. In recent years, a number of 3D-printed structures inspired by the dermal armors of various fishes have been developed to study their multiple mechanical functionalities, including flexible protection, improved hydrodynamics, body support, or tail prehensility. Natural fish armors are generally classified according to their shape, material and structural properties as elasmoid scales, ganoid scales, placoid scales, carapace scutes, or bony plates. Each type of dermal armor forms distinct articulation patterns that facilitate different functional advantages. In this paper, we highlight recent studies that developed 3D-printed structures not only to inform the design and application of some articulated and multi-material structures, but also to explain the mechanics of the natural biological systems they mimic. Copyright © 2017 Elsevier Ltd. All rights reserved.

Structuralism, Post-Structuralism, and Neo-Liberalism: Assessing Foucault's Legacy.

ERIC Educational Resources Information Center

Olssen, Mark

2003-01-01

Traces Foucault's distinctive commitment to "post-structuralism." Argues that under the influence of Nietzsche, Foucault's approach marks a distinct break with structuralism in several crucial aspects. What results is a materialist post-structuralism that is also distinctively different from the post-structuralism of Derrida, Lyotard,…

Multiple origins of interdependent endosymbiotic complexes in a genus of cicadas.

PubMed

Łukasik, Piotr; Nazario, Katherine; Van Leuven, James T; Campbell, Matthew A; Meyer, Mariah; Michalik, Anna; Pessacq, Pablo; Simon, Chris; Veloso, Claudio; McCutcheon, John P

2018-01-09

Bacterial endosymbionts that provide nutrients to hosts often have genomes that are extremely stable in structure and gene content. In contrast, the genome of the endosymbiont Hodgkinia cicadicola has fractured into multiple distinct lineages in some species of the cicada genus Tettigades To better understand the frequency, timing, and outcomes of Hodgkinia lineage splitting throughout this cicada genus, we sampled cicadas over three field seasons in Chile and performed genomics and microscopy on representative samples. We found that a single ancestral Hodgkinia lineage has split at least six independent times in Tettigades over the last 4 million years, resulting in complexes of between two and six distinct Hodgkinia lineages per host. Individual genomes in these symbiotic complexes differ dramatically in relative abundance, genome size, organization, and gene content. Each Hodgkinia lineage retains a small set of core genes involved in genetic information processing, but the high level of gene loss experienced by all genomes suggests that extensive sharing of gene products among symbiont cells must occur. In total, Hodgkinia complexes that consist of multiple lineages encode nearly complete sets of genes present on the ancestral single lineage and presumably perform the same functions as symbionts that have not undergone splitting. However, differences in the timing of the splits, along with dissimilar gene loss patterns on the resulting genomes, have led to very different outcomes of lineage splitting in extant cicadas.

Yeast ribonuclease III uses a network of multiple hydrogen bonds for RNA binding and cleavage.

PubMed

Lavoie, Mathieu; Abou Elela, Sherif

2008-08-19

Members of the bacterial RNase III family recognize a variety of short structured RNAs with few common features. It is not clear how this group of enzymes supports high cleavage fidelity while maintaining a broad base of substrates. Here we show that the yeast orthologue of RNase III (Rnt1p) uses a network of 2'-OH-dependent interactions to recognize substrates with different structures. We designed a series of bipartite substrates permitting the distinction between binding and cleavage defects. Each substrate was engineered to carry a single or multiple 2'- O-methyl or 2'-fluoro ribonucleotide substitutions to prevent the formation of hydrogen bonds with a specific nucleotide or group of nucleotides. Interestingly, introduction of 2'- O-methyl ribonucleotides near the cleavage site increased the rate of catalysis, indicating that 2'-OH are not required for cleavage. Substitution of nucleotides in known Rnt1p binding site with 2'- O-methyl ribonucleotides inhibited cleavage while single 2'-fluoro ribonucleotide substitutions did not. This indicates that while no single 2'-OH is essential for Rnt1p cleavage, small changes in the substrate structure are not tolerated. Strikingly, several nucleotide substitutions greatly increased the substrate dissociation constant with little or no effect on the Michaelis-Menten constant or rate of catalysis. Together, the results indicate that Rnt1p uses a network of nucleotide interactions to identify its substrate and support two distinct modes of binding. One mode is primarily mediated by the dsRNA binding domain and leads to the formation of stable RNA/protein complex, while the other requires the presence of the nuclease and N-terminal domains and leads to RNA cleavage.

Structural and functional connectivity between the lateral posterior-pulvinar complex and primary visual cortex in the ferret.

PubMed

Yu, Chunxiu; Sellers, Kristin K; Radtke-Schuller, Susanne; Lu, Jinghao; Xing, Lei; Ghukasyan, Vladimir; Li, Yuhui; Shih, Yen-Yu I; Murrow, Richard; Fröhlich, Flavio

2016-01-01

The role of higher-order thalamic structures in sensory processing remains poorly understood. Here, we used the ferret (Mustela putorius furo) as a novel model species for the study of the lateral posterior (LP)-pulvinar complex and its structural and functional connectivity with area 17 [primary visual cortex (V1)]. We found reciprocal anatomical connections between the lateral part of the LP nucleus of the LP-pulvinar complex (LPl) and V1. In order to investigate the role of this feedback loop between LPl and V1 in shaping network activity, we determined the functional interactions between LPl and the supragranular, granular and infragranular layers of V1 by recording multiunit activity and local field potentials. Coherence was strongest between LPl and the supragranular V1, with the most distinct peaks in the delta and alpha frequency bands. Inter-area interaction measured by spike-phase coupling identified the delta frequency band being dominated by the infragranular V1 and multiple frequency bands that were most pronounced in the supragranular V1. This inter-area coupling was differentially modulated by full-field synthetic and naturalistic visual stimulation. We also found that visual responses in LPl were distinct from those in V1 in terms of their reliability. Together, our data support a model of multiple communication channels between LPl and the layers of V1 that are enabled by oscillations in different frequency bands. This demonstration of anatomical and functional connectivity between LPl and V1 in ferrets provides a roadmap for studying the interaction dynamics during behaviour, and a template for identifying the activity dynamics of other thalamo-cortical feedback loops. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Mathematical analysis of a multiple strain, multi-locus-allele system for antigenically variable infectious diseases revisited.

PubMed

Cherif, Alhaji

2015-09-01

Many important pathogens such as HIV/AIDS, influenza, malaria, dengue and meningitis generally exist in phenotypically distinct serotypes that compete for hosts. Models used to study these diseases appear as meta-population systems. Herein, we revisit one of the multiple strain models that have been used to investigate the dynamics of infectious diseases with co-circulating serotypes or strains, and provide analytical results underlying the numerical investigations. In particular, we establish the necessary conditions for the local asymptotic stability of the steady states and for the existence of oscillatory behaviors via Hopf bifurcation. In addition, we show that the existence of discrete antigenic forms among pathogens can either fully or partially self-organize, where (i) strains exhibit no strain structures and coexist or (ii) antigenic variants sort into non-overlapping or minimally overlapping clusters that either undergo the principle of competitive exclusion exhibiting discrete strain structures, or co-exist cyclically. Copyright © 2015. Published by Elsevier Inc.

The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: The second clinical candidate having a shorter and favorable human half-life

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

Wang, Jane L.; Limburg, David; Graneto, Matthew J.

2012-05-29

In this Letter, we provide the structure-activity relationships, optimization of design, testing criteria, and human half-life data for a series of selective COX-2 inhibitors. During the course of our structure-based drug design efforts, we discovered two distinct binding modes within the COX-2 active site for differently substituted members of this class. The challenge of a undesirably long human half-life for the first clinical candidate 1t{sub 1/2} = 360 h was addressed by multiple strategies, leading to the discovery of 29b-(S) (SC-75416) with t{sub 1/2} = 34 h.

Social phobia: further evidence of dimensional structure.

PubMed

Crome, Erica; Baillie, Andrew; Slade, Tim; Ruscio, Ayelet Meron

2010-11-01

Social phobia is a common mental disorder associated with significant impairment. Current research and treatment models of social phobia rely on categorical diagnostic conceptualizations lacking empirical support. This study aims to further research exploring whether social phobia is best conceptualized as a dimension or a discrete categorical disorder. This study used three distinct taxometric techniques (mean above minus below a cut, maximum Eigen value and latent mode) to explore the latent structure of social phobia in two large epidemiological samples, using indicators derived from diagnostic criteria and associated avoidant personality traits. Overall, outcomes from multiple taxometric analyses supported dimensional structure. This is consistent with conceptualizations of social phobia as lying on a continuum with avoidant personality traits. Support for the dimensionality of social phobia has important implications for future research, assessment, treatment, and public policy.

Structurally complex and highly active RNA ligases derived from random RNA sequences

NASA Technical Reports Server (NTRS)

Ekland, E. H.; Szostak, J. W.; Bartel, D. P.

1995-01-01

Seven families of RNA ligases, previously isolated from random RNA sequences, fall into three classes on the basis of secondary structure and regiospecificity of ligation. Two of the three classes of ribozymes have been engineered to act as true enzymes, catalyzing the multiple-turnover transformation of substrates into products. The most complex of these ribozymes has a minimal catalytic domain of 93 nucleotides. An optimized version of this ribozyme has a kcat exceeding one per second, a value far greater than that of most natural RNA catalysts and approaching that of comparable protein enzymes. The fact that such a large and complex ligase emerged from a very limited sampling of sequence space implies the existence of a large number of distinct RNA structures of equivalent complexity and activity.

Bioactivities, isolation and purification methods of polysaccharides from natural products: A review.

PubMed

Shi, Lei

2016-11-01

Polysaccharides play multiple roles and have extensive bioactivities in life process and an immense potential in healthcare, food and cosmetic industries, due to their therapeutic effects and relatively low toxicity. This review describes their major functions involved in antitumor, anti-virus, and anti-inflammatory bioactivities. Due to their enormous structural heterogeneity, the approaches for isolation and purification of polysaccharides are distinct from that of the other macromolecules such as proteins, etc. Yet, to achieve the homogeneity is the initial step for studies of polysaccharide structure, pharmacology, and its structure-activity relationships. According to the experiences accumulated by our lab and the published literatures, this review also introduces the methods widely used in isolation and purification of polysaccharides. Copyright © 2016 Elsevier B.V. All rights reserved.

On the universal structure of human lexical semantics

DOE PAGES

Youn, Hyejin; Sutton, Logan; Smith, Eric; ...

2016-02-01

How universal is human conceptual structure? The way concepts are organized in the human brain may reflect distinct features of cultural, historical, and environmental background in addition to properties universal to human cognition. Semantics, or meaning expressed through language, provides indirect access to the underlying conceptual structure, but meaning is notoriously difficult to measure, let alone parameterize. Here, we provide an empirical measure of semantic proximity between concepts using cross-linguistic dictionaries to translate words to and from languages carefully selected to be representative of worldwide diversity. These translations reveal cases where a particular language uses a single “polysemous” word tomore » express multiple concepts that another language represents using distinct words. We use the frequency of such polysemies linking two concepts as a measure of their semantic proximity and represent the pattern of these linkages by a weighted network. This network is highly structured: Certain concepts are far more prone to polysemy than others, and naturally interpretable clusters of closely related concepts emerge. Statistical analysis of the polysemies observed in a subset of the basic vocabulary shows that these structural properties are consistent across different language groups, and largely independent of geography, environment, and the presence or absence of a literary tradition. As a result, the methods developed here can be applied to any semantic domain to reveal the extent to which its conceptual structure is, similarly, a universal attribute of human cognition and language use.« less

On the universal structure of human lexical semantics

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

Youn, Hyejin; Sutton, Logan; Smith, Eric

How universal is human conceptual structure? The way concepts are organized in the human brain may reflect distinct features of cultural, historical, and environmental background in addition to properties universal to human cognition. Semantics, or meaning expressed through language, provides indirect access to the underlying conceptual structure, but meaning is notoriously difficult to measure, let alone parameterize. Here, we provide an empirical measure of semantic proximity between concepts using cross-linguistic dictionaries to translate words to and from languages carefully selected to be representative of worldwide diversity. These translations reveal cases where a particular language uses a single “polysemous” word tomore » express multiple concepts that another language represents using distinct words. We use the frequency of such polysemies linking two concepts as a measure of their semantic proximity and represent the pattern of these linkages by a weighted network. This network is highly structured: Certain concepts are far more prone to polysemy than others, and naturally interpretable clusters of closely related concepts emerge. Statistical analysis of the polysemies observed in a subset of the basic vocabulary shows that these structural properties are consistent across different language groups, and largely independent of geography, environment, and the presence or absence of a literary tradition. As a result, the methods developed here can be applied to any semantic domain to reveal the extent to which its conceptual structure is, similarly, a universal attribute of human cognition and language use.« less

Separation and identification of structural isomers by quadrupole collision-induced dissociation-hydrogen/deuterium exchange-infrared multiphoton dissociation (QCID-HDX-IRMPD).

PubMed

Gucinski, Ashley C; Somogyi, Arpád; Chamot-Rooke, Julia; Wysocki, Vicki H

2010-08-01

A new approach that uses a hybrid Q-FTICR instrument and combines quadrupole collision-induced dissociation, hydrogen-deuterium exchange, and infrared multiphoton dissociation (QCID-HDX-IRMPD) has been shown to effectively separate and differentiate isomeric fragment ion structures present at the same m/z. This method was used to study protonated YAGFL-OH (free acid), YAGFL-NH(2) (amide), cyclic YAGFL, and YAGFL-OCH(3) (methyl ester). QCID-HDX of m/z 552.28 (C(29)H(38)N(5)O(6)) from YAGFL-OH reveals at least two distributions of ions corresponding to the b(5) ion and a non-C-terminal water loss ion structure. Subsequent IRMPD fragmentation of each population shows distinct fragmentation patterns, reflecting the different structures from which they arise. This contrasts with data for YAGFL-NH(2) and YAGFL-OCH(3), which do not show two distinct H/D exchange populations for the C(29)H(38)N(5)O(6) structure formed by NH(3) and HOCH(3) loss, respectively. Relative extents of exchange for C(29)H(38)N(5)O(6) ions from six sequence isomers (YAGFL, AGFLY, GFLYA, FLYAG, LYAGF, and LFGAY) show a sequence dependence of relative isomer abundance. Supporting action IRMPD spectroscopy data are also presented herein and also show that multiple structures are present for the C(29)H(38)N(5)O(6) species from YAGFL-OH. Copyright 2010. Published by Elsevier Inc.

Unified thalamic model generates multiple distinct oscillations with state-dependent entrainment by stimulation

PubMed Central

2017-01-01

The thalamus plays a critical role in the genesis of thalamocortical oscillations, yet the underlying mechanisms remain elusive. To understand whether the isolated thalamus can generate multiple distinct oscillations, we developed a biophysical thalamic model to test the hypothesis that generation of and transition between distinct thalamic oscillations can be explained as a function of neuromodulation by acetylcholine (ACh) and norepinephrine (NE) and afferent synaptic excitation. Indeed, the model exhibited four distinct thalamic rhythms (delta, sleep spindle, alpha and gamma oscillations) that span the physiological states corresponding to different arousal levels from deep sleep to focused attention. Our simulation results indicate that generation of these distinct thalamic oscillations is a result of both intrinsic oscillatory cellular properties and specific network connectivity patterns. We then systematically varied the ACh/NE and input levels to generate a complete map of the different oscillatory states and their transitions. Lastly, we applied periodic stimulation to the thalamic network and found that entrainment of thalamic oscillations is highly state-dependent. Our results support the hypothesis that ACh/NE modulation and afferent excitation define thalamic oscillatory states and their response to brain stimulation. Our model proposes a broader and more central role of the thalamus in the genesis of multiple distinct thalamo-cortical rhythms than previously assumed. PMID:29073146

R3D-2-MSA: the RNA 3D structure-to-multiple sequence alignment server

PubMed Central

Cannone, Jamie J.; Sweeney, Blake A.; Petrov, Anton I.; Gutell, Robin R.; Zirbel, Craig L.; Leontis, Neocles

2015-01-01

The RNA 3D Structure-to-Multiple Sequence Alignment Server (R3D-2-MSA) is a new web service that seamlessly links RNA three-dimensional (3D) structures to high-quality RNA multiple sequence alignments (MSAs) from diverse biological sources. In this first release, R3D-2-MSA provides manual and programmatic access to curated, representative ribosomal RNA sequence alignments from bacterial, archaeal, eukaryal and organellar ribosomes, using nucleotide numbers from representative atomic-resolution 3D structures. A web-based front end is available for manual entry and an Application Program Interface for programmatic access. Users can specify up to five ranges of nucleotides and 50 nucleotide positions per range. The R3D-2-MSA server maps these ranges to the appropriate columns of the corresponding MSA and returns the contents of the columns, either for display in a web browser or in JSON format for subsequent programmatic use. The browser output page provides a 3D interactive display of the query, a full list of sequence variants with taxonomic information and a statistical summary of distinct sequence variants found. The output can be filtered and sorted in the browser. Previous user queries can be viewed at any time by resubmitting the output URL, which encodes the search and re-generates the results. The service is freely available with no login requirement at http://rna.bgsu.edu/r3d-2-msa. PMID:26048960

The Embryonic Septum and Ventral Pallium, New Sources of Olfactory Cortex Cells

PubMed Central

de Carlos, Juan A.

2012-01-01

The mammalian olfactory cortex is a complex structure located along the rostro-caudal extension of the ventrolateral prosencephalon, which is divided into several anatomically and functionally distinct areas: the anterior olfactory nucleus, piriform cortex, olfactory tubercle, amygdaloid olfactory nuclei, and the more caudal entorhinal cortex. Multiple forebrain progenitor domains contribute to the cellular diversity of the olfactory cortex, which is invaded simultaneously by cells originating in distinct germinal areas in the dorsal and ventral forebrain. Using a combination of dye labeling techniques, we identified two novel areas that contribute cells to the developing olfactory cortices, the septum and the ventral pallium, from which cells migrate along a radial and then a tangential path. We characterized these cell populations by comparing their expression of calretinin, calbindin, reelin and Tbr1 with that of other olfactory cell populations. PMID:22984546

Framing life and death on YouTube: the strategic communication of organ donation messages by organ procurement organizations.

PubMed

VanderKnyff, Jeremy; Friedman, Daniela B; Tanner, Andrea

2015-01-01

Using a sample of YouTube videos posted on the YouTube channels of organ procurement organizations, a content analysis was conducted to identify the frames used to strategically communicate prodonation messages. A total of 377 videos were coded for general characteristics, format, speaker characteristics, organs discussed, structure, problem definition, and treatment. Principal components analysis identified message frames, and k-means cluster analysis established distinct groupings of videos on the basis of the strength of their relationship to message frames. Analysis of these frames and clusters found that organ procurement organizations present multiple, and sometimes competing, video types and message frames on YouTube. This study serves as important formative research that will inform future studies to measure the effectiveness of the distinct message frames and clusters identified.

Differential expression and activation of a family of murine peroxisome proliferator-activated receptors.

PubMed Central

Kliewer, S A; Forman, B M; Blumberg, B; Ong, E S; Borgmeyer, U; Mangelsdorf, D J; Umesono, K; Evans, R M

1994-01-01

To gain insight into the function of peroxisome proliferator-activated receptor (PPAR) isoforms in mammals, we have cloned and characterized two PPAR alpha-related cDNAs (designated PPAR gamma and -delta, respectively) from mouse. The three PPAR isoforms display widely divergent patterns of expression during embryogenesis and in the adult. Surprisingly, PPAR gamma and -delta are not activated by pirinixic acid (Wy 14,643), a potent peroxisome proliferator and activator of PPAR alpha. However, PPAR gamma and -delta are activated by the structurally distinct peroxisome proliferator LY-171883 and linoleic acid, respectively, indicating that each of the isoforms can act as a regulated activator of transcription. These data suggest that tissue-specific responsiveness to peroxisome proliferators, including certain fatty acids, is in part a consequence of differential expression of multiple, pharmacologically distinct PPAR isoforms. Images PMID:8041794

Region-Urbanicity Differences in Locus of Control: Social Disadvantage, Structure, or Cultural Exceptionalism?

PubMed

Shifrer, Dara; Sutton, April

2014-11-01

People with internal rather than external locus of control experience better outcomes in multiple domains. Previous studies on spatial differences in control within America only focused on the South, relied on aggregate level data or historical evidence, or did not account for other confounding regional distinctions (such as variation in urbanicity). Using data from the National Education Longitudinal Study, we find differences in adolescents' loci of control depending on their region and urbanicity are largely attributable to differences in their social background, and only minimally to structural differences (i.e., differences in the qualities of adolescents' schools). Differences that persist net of differences across adolescents and their schools suggest the less internal control of rural Southern adolescents, and the more internal control of rural and urban Northeastern adolescents, may be due to cultural distinctions in those areas. Results indicate region is more closely associated than urbanicity with differences in locus of control, with Western and Northeastern cultures seemingly fostering more internal control than Midwestern and Southern cultures. These findings contribute to research on spatial variation in a variety of psychological traits.

Region-Urbanicity Differences in Locus of Control: Social Disadvantage, Structure, or Cultural Exceptionalism?

PubMed Central

Shifrer, Dara; Sutton, April

2014-01-01

People with internal rather than external locus of control experience better outcomes in multiple domains. Previous studies on spatial differences in control within America only focused on the South, relied on aggregate level data or historical evidence, or did not account for other confounding regional distinctions (such as variation in urbanicity). Using data from the National Education Longitudinal Study, we find differences in adolescents' loci of control depending on their region and urbanicity are largely attributable to differences in their social background, and only minimally to structural differences (i.e., differences in the qualities of adolescents' schools). Differences that persist net of differences across adolescents and their schools suggest the less internal control of rural Southern adolescents, and the more internal control of rural and urban Northeastern adolescents, may be due to cultural distinctions in those areas. Results indicate region is more closely associated than urbanicity with differences in locus of control, with Western and Northeastern cultures seemingly fostering more internal control than Midwestern and Southern cultures. These findings contribute to research on spatial variation in a variety of psychological traits. PMID:25382875

Multiple structure-intrinsic disorder interactions regulate and coordinate Hox protein function

NASA Astrophysics Data System (ADS)

Bondos, Sarah

During animal development, Hox transcription factors determine fate of developing tissues to generate diverse organs and appendages. Hox proteins are famous for their bizarre mutant phenotypes, such as replacing antennae with legs. Clearly, the functions of individual Hox proteins must be distinct and reliable in vivo, or the organism risks malformation or death. However, within the Hox protein family, the DNA-binding homeodomains are highly conserved and the amino acids that contact DNA are nearly invariant. These observations raise the question: How do different Hox proteins correctly identify their distinct target genes using a common DNA binding domain? One possible means to modulate DNA binding is through the influence of the non-homeodomain protein regions, which differ significantly among Hox proteins. However genetic approaches never detected intra-protein interactions, and early biochemical attempts were hindered because the special features of ``intrinsically disordered'' sequences were not appreciated. We propose the first-ever structural model of a Hox protein to explain how specific contacts between distant, intrinsically disordered regions of the protein and the homeodomain regulate DNA binding and coordinate this activity with other Hox molecular functions.

TanCAR: A Novel Bispecific Chimeric Antigen Receptor for Cancer Immunotherapy

PubMed Central

Grada, Zakaria; Hegde, Meenakshi; Byrd, Tiara; Shaffer, Donald R; Ghazi, Alexia; Brawley, Vita S; Corder, Amanda; Schönfeld, Kurt; Koch, Joachim; Dotti, Gianpietro; Heslop, Helen E; Gottschalk, Stephen; Wels, Winfried S; Baker, Matthew L; Ahmed, Nabil

2013-01-01

Targeted T cells are emerging as effective non-toxic therapies for cancer. Multiple elements, however, contribute to the overall pathogenesis of cancer through both distinct and redundant mechanisms. Hence, targeting multiple cancer-specific markers simultaneously could result in better therapeutic efficacy. We created a functional chimeric antigen receptor—the TanCAR, a novel artificial molecule that mediates bispecific activation and targeting of T cells. We demonstrate the feasibility of cumulative integration of structure and docking simulation data using computational tools to interrogate the design and predict the functionality of such a complex bispecific molecule. Our prototype TanCAR induced distinct T cell reactivity against each of two tumor restricted antigens, and produced synergistic enhancement of effector functions when both antigens were simultaneously encountered. Furthermore, the TanCAR preserved the cytolytic ability of T cells upon loss of one of the target molecules and better controlled established experimental tumors by recognition of both targets in an animal disease model. This proof-of-concept approach can be used to increase the specificity of effector cells for malignant versus normal target cells, to offset antigen escape or to allow for targeting the tumor and its microenvironment. PMID:23839099

Risk factors for fecal colonization with multiple distinct strains of Escherichia coli among long-term care facility residents.

PubMed

Lautenbach, Ebbing; Tolomeo, Pam; Black, Nicole; Maslow, Joel N

2009-05-01

Of 49 long-term care facility residents, 21 (43%) were colonized with 2 or more distinct strains of Escherichia coli. There were no significant risk factors for colonization with multiple strains of E. coli. These results suggest that future efforts to efficiently identify the diversity of colonizing strains will be challenging.

Risk Factors for Fecal Colonization with Multiple Distinct Strains of Escherichia coli Among Long-Term Care Facility Residents

PubMed Central

Lautenbach, Ebbing; Tolomeo, Pam; Black, Nicole; Maslow, Joel N.

2009-01-01

Of 49 long-term care facility residents, 21 (43%) were colonized with two or more distinct strains of Escherichia coli. There were no significant risk factors for colonization with multiple strains of E. coli. These results suggest future efforts to efficiently identify diversity of colonizing strains will be challenging. PMID:19292660

Enhanced protective role in materials with gradient structural orientations: Lessons from Nature.

PubMed

Liu, Zengqian; Zhu, Yankun; Jiao, Da; Weng, Zhaoyong; Zhang, Zhefeng; Ritchie, Robert O

2016-10-15

Living organisms are adept at resisting contact deformation and damage by assembling protective surfaces with spatially varied mechanical properties, i.e., by creating functionally graded materials. Such gradients, together with multiple length-scale hierarchical structures, represent the two prime characteristics of many biological materials to be translated into engineering design. Here, we examine one design motif from a variety of biological tissues and materials where site-specific mechanical properties are generated for enhanced protection by adopting gradients in structural orientation over multiple length-scales, without manipulation of composition or microstructural dimension. Quantitative correlations are established between the structural orientations and local mechanical properties, such as stiffness, strength and fracture resistance; based on such gradients, the underlying mechanisms for the enhanced protective role of these materials are clarified. Theoretical analysis is presented and corroborated through numerical simulations of the indentation behavior of composites with distinct orientations. The design strategy of such bioinspired gradients is outlined in terms of the geometry of constituents. This study may offer a feasible approach towards generating functionally graded mechanical properties in synthetic materials for improved contact damage resistance. Living organisms are adept at resisting contact damage by assembling protective surfaces with spatially varied mechanical properties, i.e., by creating functionally-graded materials. Such gradients, together with multiple length-scale hierarchical structures, represent the prime characteristics of many biological materials. Here, we examine one design motif from a variety of biological tissues where site-specific mechanical properties are generated for enhanced protection by adopting gradients in structural orientation at multiple length-scales, without changes in composition or microstructural dimension. The design strategy of such bioinspired gradients is outlined in terms of the geometry of constituents. This study may offer a feasible approach towards generating functionally-graded mechanical properties in synthetic materials for improved damage resistance. Published by Elsevier Ltd.

Intrinsic hierarchical structural imperfections in a natural ceramic of bivalve shell with distinctly graded properties

PubMed Central

Jiao, Da; Liu, Zengqian; Zhang, Zhenjun; Zhang, Zhefeng

2015-01-01

Despite the extensive investigation on the structure of natural biological materials, insufficient attention has been paid to the structural imperfections by which the mechanical properties of synthetic materials are dominated. In this study, the structure of bivalve Saxidomus purpuratus shell has been systematically characterized quantitatively on multiple length scales from millimeter to sub-nanometer. It is revealed that hierarchical imperfections are intrinsically involved in the crossed-lamellar structure of the shell despite its periodically packed platelets. In particular, various favorable characters which are always pursued in synthetic materials, e.g. nanotwins and low-angle misorientations, have been incorporated herein. The possible contributions of these imperfections to mechanical properties are further discussed. It is suggested that the imperfections may serve as structural adaptations, rather than detrimental defects in the real sense, to help improve the mechanical properties of natural biological materials. This study may aid in understanding the optimizing strategies of structure and properties designed by nature, and accordingly, provide inspiration for the design of synthetic materials. PMID:26198844

Intrinsic hierarchical structural imperfections in a natural ceramic of bivalve shell with distinctly graded properties.

PubMed

Jiao, Da; Liu, Zengqian; Zhang, Zhenjun; Zhang, Zhefeng

2015-07-22

Despite the extensive investigation on the structure of natural biological materials, insufficient attention has been paid to the structural imperfections by which the mechanical properties of synthetic materials are dominated. In this study, the structure of bivalve Saxidomus purpuratus shell has been systematically characterized quantitatively on multiple length scales from millimeter to sub-nanometer. It is revealed that hierarchical imperfections are intrinsically involved in the crossed-lamellar structure of the shell despite its periodically packed platelets. In particular, various favorable characters which are always pursued in synthetic materials, e.g. nanotwins and low-angle misorientations, have been incorporated herein. The possible contributions of these imperfections to mechanical properties are further discussed. It is suggested that the imperfections may serve as structural adaptations, rather than detrimental defects in the real sense, to help improve the mechanical properties of natural biological materials. This study may aid in understanding the optimizing strategies of structure and properties designed by nature, and accordingly, provide inspiration for the design of synthetic materials.

Stress Effects on Multiple Memory System Interactions

PubMed Central

Ness, Deborah; Calabrese, Pasquale

2016-01-01

Extensive behavioural, pharmacological, and neurological research reports stress effects on mammalian memory processes. While stress effects on memory quantity have been known for decades, the influence of stress on multiple memory systems and their distinct contributions to the learning process have only recently been described. In this paper, after summarizing the fundamental biological aspects of stress/emotional arousal and recapitulating functionally and anatomically distinct memory systems, we review recent animal and human studies exploring the effects of stress on multiple memory systems. Apart from discussing the interaction between distinct memory systems in stressful situations, we will also outline the fundamental role of the amygdala in mediating such stress effects. Additionally, based on the methods applied in the herein discussed studies, we will discuss how memory translates into behaviour. PMID:27034845

Resolving the Chemically Discrete Structure of Synthetic Borophene Polymorphs.

PubMed

Campbell, Gavin P; Mannix, Andrew J; Emery, Jonathan D; Lee, Tien-Lin; Guisinger, Nathan P; Hersam, Mark C; Bedzyk, Michael J

2018-05-09

Atomically thin two-dimensional (2D) materials exhibit superlative properties dictated by their intralayer atomic structure, which is typically derived from a limited number of thermodynamically stable bulk layered crystals (e.g., graphene from graphite). The growth of entirely synthetic 2D crystals, those with no corresponding bulk allotrope, would circumvent this dependence upon bulk thermodynamics and substantially expand the phase space available for structure-property engineering of 2D materials. However, it remains unclear if synthetic 2D materials can exist as structurally and chemically distinct layers anchored by van der Waals (vdW) forces, as opposed to strongly bound adlayers. Here, we show that atomically thin sheets of boron (i.e., borophene) grown on the Ag(111) surface exhibit a vdW-like structure without a corresponding bulk allotrope. Using X-ray standing wave-excited X-ray photoelectron spectroscopy, the positions of boron in multiple chemical states are resolved with sub-angström spatial resolution, revealing that the borophene forms a single planar layer that is 2.4 Å above the unreconstructed Ag surface. Moreover, our results reveal that multiple borophene phases exhibit these characteristics, denoting a unique form of polymorphism consistent with recent predictions. This observation of synthetic borophene as chemically discrete from the growth substrate suggests that it is possible to engineer a much wider variety of 2D materials than those accessible through bulk layered crystal structures.

Inquiry in conversation: Exploring the multiple solution pathway (MSP) lesson structure as a means to progressive discourse in the science classroom

NASA Astrophysics Data System (ADS)

Criswell, Brett A.

This exploratory, descriptive study examined the way five chemistry teachers from four different schools enacted their visions of an activity labeled as the multiple solution pathway (MSP) lesson structure -- one in which students were given a relevant problem to solve and the opportunity to propose and explore several solutions to the problem. A theoretical and analytical framework for characterizing what transpired within these enactments was developed mainly out of Bereiter's principle of progressive discourse and its accompanying commitments, but also by drawing on Peirce's fallibilist epistemology, Gal'perin's notion of the orienting basis of an action, and Davydov's distinction between empirical and theoretical generalizations. Data from utterance-level discourse analysis of the videotaped lessons, supplemented by pre- and post-lesson interviews with both students and teachers was used to answer the research question: What is the nature of the interactions that occur during Multiple Solution Pathway (MSP) lessons and how are those interactions related to the structure of activity and the way in which ideas are explored within those lessons? The data showed that there were two general structures of activity utilized by the five teachers and that these different structures impacted the extent to which two of the progressive discourse commitments (expansion and openness) were supported. It also indicated that the teachers likely operated off a 'teacher as evaluator' metaphor and a discrepant event vision of the way the lesson should unfold, both features of which limited the extent to which progressive discourse was maintained in these lessons. Pedagogical implications for more fully realizing the potential of the MSP structure are presented.

Multiscale Feature Analysis of Salivary Gland Branching Morphogenesis

PubMed Central

Baydil, Banu; Daley, William P.; Larsen, Melinda; Yener, Bülent

2012-01-01

Pattern formation in developing tissues involves dynamic spatio-temporal changes in cellular organization and subsequent evolution of functional adult structures. Branching morphogenesis is a developmental mechanism by which patterns are generated in many developing organs, which is controlled by underlying molecular pathways. Understanding the relationship between molecular signaling, cellular behavior and resulting morphological change requires quantification and categorization of the cellular behavior. In this study, tissue-level and cellular changes in developing salivary gland in response to disruption of ROCK-mediated signaling by are modeled by building cell-graphs to compute mathematical features capturing structural properties at multiple scales. These features were used to generate multiscale cell-graph signatures of untreated and ROCK signaling disrupted salivary gland organ explants. From confocal images of mouse submandibular salivary gland organ explants in which epithelial and mesenchymal nuclei were marked, a multiscale feature set capturing global structural properties, local structural properties, spectral, and morphological properties of the tissues was derived. Six feature selection algorithms and multiway modeling of the data was performed to identify distinct subsets of cell graph features that can uniquely classify and differentiate between different cell populations. Multiscale cell-graph analysis was most effective in classification of the tissue state. Cellular and tissue organization, as defined by a multiscale subset of cell-graph features, are both quantitatively distinct in epithelial and mesenchymal cell types both in the presence and absence of ROCK inhibitors. Whereas tensor analysis demonstrate that epithelial tissue was affected the most by inhibition of ROCK signaling, significant multiscale changes in mesenchymal tissue organization were identified with this analysis that were not identified in previous biological studies. We here show how to define and calculate a multiscale feature set as an effective computational approach to identify and quantify changes at multiple biological scales and to distinguish between different states in developing tissues. PMID:22403724

Emerging structural insights into the function of ionotropic glutamate receptors.

PubMed

Karakas, Erkan; Regan, Michael C; Furukawa, Hiro

2015-06-01

Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate excitatory neurotransmission crucial for brain development and function, including learning and memory formation. Recently a wealth of structural studies on iGluRs including AMPA receptors (AMPARs), kainate receptors, and NMDA receptors (NMDARs) became available. These studies showed structures of non-NMDARs including AMPAR and kainate receptor in various functional states, thereby providing the first visual sense of how non-NMDAR iGluRs may function in the context of homotetramers. Furthermore, they provided the first view of heterotetrameric NMDAR ion channels, and this illuminated the similarities with and differences from non-NMDARs, thus raising a mechanistic distinction between the two groups of iGluRs. We review mechanistic insights into iGluR functions gained through structural studies of multiple groups. Copyright © 2015 Elsevier Ltd. All rights reserved.

Toddlers Default to Canonical Surface-to-Meaning Mapping When Learning Verbs

PubMed Central

Dautriche, Isabelle; Cristia, Alejandrina; Brusini, Perrine; Yuan, Sylvia; Fisher, Cynthia; Christophe, Anne

2013-01-01

Previous work has shown that toddlers readily encode each noun in the sentence as a distinct argument of the verb. However, languages allow multiple mappings between form and meaning which do not fit this canonical format. Two experiments examined French 28-month-olds’ interpretation of right-dislocated sentences (nouni-verb, nouni) where the presence of clear, language-specific cues should block such a canonical mapping. Toddlers (N = 96) interpreted novel verbs embedded in these sentences as transitive, disregarding prosodic cues to dislocation (Experiment 1) but correctly interpreted right-dislocated sentences containing well-known verbs (Experiment 2). These results suggest that toddlers can integrate multiple cues in ideal conditions, but default to canonical surface-to-meaning mapping when extracting structural information about novel verbs in semantically impoverished conditions. PMID:24117408

Passive band-gap reconfiguration born from bifurcation asymmetry.

PubMed

Bernard, Brian P; Mann, Brian P

2013-11-01

Current periodic structures are constrained to have fixed energy transmission behavior unless active control or component replacement is used to alter their wave propagation characteristics. The introduction of nonlinearity to generate multiple stable equilibria is an alternative strategy for realizing distinct energy propagation behaviors. We investigate the creation of a reconfigurable band-gap system by implementing passive switching between multiple stable states of equilibrium, to alter the level of energy attenuation in response to environmental stimuli. The ability to avoid potentially catastrophic loads is demonstrated by tailoring the bandpass and band-gap regions to coalesce for two stable equilibria and varying an external load parameter to trigger a bifurcation. The proposed phenomenon could be utilized in remote or autonomous applications where component modifications and active control are impractical.

Basic level category structure emerges gradually across human ventral visual cortex.

PubMed

Iordan, Marius Cătălin; Greene, Michelle R; Beck, Diane M; Fei-Fei, Li

2015-07-01

Objects can be simultaneously categorized at multiple levels of specificity ranging from very broad ("natural object") to very distinct ("Mr. Woof"), with a mid-level of generality (basic level: "dog") often providing the most cognitively useful distinction between categories. It is unknown, however, how this hierarchical representation is achieved in the brain. Using multivoxel pattern analyses, we examined how well each taxonomic level (superordinate, basic, and subordinate) of real-world object categories is represented across occipitotemporal cortex. We found that, although in early visual cortex objects are best represented at the subordinate level (an effect mostly driven by low-level feature overlap between objects in the same category), this advantage diminishes compared to the basic level as we move up the visual hierarchy, disappearing in object-selective regions of occipitotemporal cortex. This pattern stems from a combined increase in within-category similarity (category cohesion) and between-category dissimilarity (category distinctiveness) of neural activity patterns at the basic level, relative to both subordinate and superordinate levels, suggesting that successive visual areas may be optimizing basic level representations.

Clustering of disulfide-rich peptides provides scaffolds for hit discovery by phage display: application to interleukin-23.

PubMed

Barkan, David T; Cheng, Xiao-Li; Celino, Herodion; Tran, Tran T; Bhandari, Ashok; Craik, Charles S; Sali, Andrej; Smythe, Mark L

2016-11-23

Disulfide-rich peptides (DRPs) are found throughout nature. They are suitable scaffolds for drug development due to their small cores, whose disulfide bonds impart extraordinary chemical and biological stability. A challenge in developing a DRP therapeutic is to engineer binding to a specific target. This challenge can be overcome by (i) sampling the large sequence space of a given scaffold through a phage display library and by (ii) panning multiple libraries encoding structurally distinct scaffolds. Here, we implement a protocol for defining these diverse scaffolds, based on clustering structurally defined DRPs according to their conformational similarity. We developed and applied a hierarchical clustering protocol based on DRP structural similarity, followed by two post-processing steps, to classify 806 unique DRP structures into 81 clusters. The 20 most populated clusters comprised 85% of all DRPs. Representative scaffolds were selected from each of these clusters; the representatives were structurally distinct from one another, but similar to other DRPs in their respective clusters. To demonstrate the utility of the clusters, phage libraries were constructed for three of the representative scaffolds and panned against interleukin-23. One library produced a peptide that bound to this target with an IC 50 of 3.3 μM. Most DRP clusters contained members that were diverse in sequence, host organism, and interacting proteins, indicating that cluster members were functionally diverse despite having similar structure. Only 20 peptide scaffolds accounted for most of the natural DRP structural diversity, providing suitable starting points for seeding phage display experiments. Through selection of the scaffold surface to vary in phage display, libraries can be designed that present sequence diversity in architecturally distinct, biologically relevant combinations of secondary structures. We supported this hypothesis with a proof-of-concept experiment in which three phage libraries were constructed and panned against the IL-23 target, resulting in a single-digit μM hit and suggesting that a collection of libraries based on the full set of 20 scaffolds increases the potential to identify efficiently peptide binders to a protein target in a drug discovery program.

Antecedents of Coping with the Disease in Patients with Multiple Sclerosis: A Qualitative Content Analysis

PubMed Central

Dehghani, Ali; Dehghan Nayeri, Nahid; Ebadi, Abbas

2017-01-01

ABSTRACT Background: Due to many physical and mental disorders that occur in multiple sclerosis patients, identifying the factors affecting coping based on the experiences of patients using qualitative study is essential to improve their quality of life. This study was conducted to explore the antecedents of coping with the disease in patients with multiple sclerosis. Methods: This is a qualitative study conducted on 11 patients with multiple sclerosis in 2015 in Tehran, Iran. These patients were selected based on purposive sampling. Data were collected using semi-structured and in-depth interviews and coded. These data were analyzed using the conventional content analysis. The rigor of qualitative data using the criteria proposed by Guba and Lincoln were assessed. Results: Five main categories were revealed: (1) social support, (2) lenience, (3) reliance on faith, (4) knowledge of multiple sclerosis and modeling, and (5) economic and environmental situation. Each category had several distinct sub-categories. Conclusions: The results of this study showed that coping with multiple sclerosis is a complex, multidimensional and contextual concept that is affected by various factors in relation to the context of Iran. The findings of the study can provide the healthcare professionals with deeper recognition and understanding of these antecedents to improve successful coping in Iranian patients suffering from multiple sclerosis. PMID:28097178

Metagenomic mining for thermostable esterolytic enzymes uncovers a new family of bacterial esterases.

PubMed

Zarafeta, Dimitra; Moschidi, Danai; Ladoukakis, Efthymios; Gavrilov, Sergey; Chrysina, Evangelia D; Chatziioannou, Aristotelis; Kublanov, Ilya; Skretas, Georgios; Kolisis, Fragiskos N

2016-12-19

Biocatalysts exerting activity against ester bonds have a broad range of applications in modern biotechnology. Here, we have identified a new esterolytic enzyme by screening a metagenomic sample collected from a hot spring in Kamchatka, Russia. Biochemical characterization of the new esterase, termed EstDZ2, revealed that it is highly active against medium chain fatty acid esters at temperatures between 25 and 60 °C and at pH values 7-8. The new enzyme is moderately thermostable with a half-life of more than six hours at 60 °C, but exhibits exquisite stability against high concentrations of organic solvents. Phylogenetic analysis indicated that EstDZ2 is likely an Acetothermia enzyme that belongs to a new family of bacterial esterases, for which we propose the index XV. One distinctive feature of this new family, is the presence of a conserved GHSAG catalytic motif. Multiple sequence alignment, coupled with computational modelling of the three-dimensional structure of EstDZ2, revealed that the enzyme lacks the largest part of the "cap" domain, whose extended structure is characteristic for the closely related Family IV esterases. Thus, EstDZ2 appears to be distinct from known related esterolytic enzymes, both in terms of sequence characteristics, as well as in terms of three-dimensional structure.

GRP94/gp96 in Cancer: Biology, Structure, Immunology, and Drug Development.

PubMed

Wu, Bill X; Hong, Feng; Zhang, Yongliang; Ansa-Addo, Ephraim; Li, Zihai

2016-01-01

As an endoplasmic reticulum heat-shock protein 90 (HSP90) paralog, GRP94 (glucose-regulated protein 94)/gp96 (hereafter referred to as GRP94) has been shown to be an essential master chaperone for multiple receptors including Toll-like receptors, Wnt coreceptors, and integrins. Clinically, expression of GRP94 correlates with advanced stage and poor survival in a variety of cancers. Recent preclinical studies have also revealed that GRP94 expression is closely linked to cancer growth and metastasis in melanoma, ovarian cancer, multiple myeloma, lung cancer, and inflammation-associated colon cancer. Thus, GRP94 is an attractive therapeutic target in a number of malignancies. The chaperone function of GRP94 depends on its ATPase domain, which is structurally distinct from HSP90, allowing design of highly selective GRP94-targeted inhibitors. In this chapter, we discuss the biology and structure-function relationship of GRP94. We also summarize the immunological roles of GRP94 based on the studies documented over the last two decades, as these pertain to tumorigenesis and cancer progression. Finally, the structure-based rationale for the design of selective small-molecule inhibitors of GRP94 and their potential application in the treatment of cancer are highlighted. © 2016 Elsevier Inc. All rights reserved.

SEM, EDS and vibrational spectroscopic study of dawsonite NaAl(CO3)(OH)2.

PubMed

Frost, Ray L; López, Andrés; Scholz, Ricardo; Sampaio, Ney Pinheiro; de Oliveira, Fernando A N

2015-02-05

In this work we have studied the mineral dawsonite by using a combination of scanning electron microscopy with EDS and vibrational spectroscopy. Single crystals show an acicular habitus forming aggregates with a rosette shape. The chemical analysis shows a phase composed of C, Al, and Na. Two distinct Raman bands at 1091 and 1068 cm(-1) are assigned to the CO3(2-) ν1 symmetric stretching mode. Multiple bands are observed in both the Raman and infrared spectra in the antisymmetric stretching and bending regions showing that the symmetry of the carbonate anion is reduced and in all probability the carbonate anions are not equivalent in the dawsonite structure. Multiple OH deformation vibrations centred upon 950 cm(-1) in both the Raman and infrared spectra show that the OH units in the dawsonite structure are non-equivalent. Raman bands observed at 3250, 3283 and 3295 cm(-1) are assigned to OH stretching vibrations. The position of these bands indicates strong hydrogen bonding of the OH units in the dawsonite structure. The formation of the mineral dawsonite has the potential to offer a mechanism for the geosequestration of greenhouse gases. Copyright © 2014 Elsevier B.V. All rights reserved.

SEM, EDS and vibrational spectroscopic study of dawsonite NaAl(CO3)(OH)2

NASA Astrophysics Data System (ADS)

Frost, Ray L.; López, Andrés; Scholz, Ricardo; Sampaio, Ney Pinheiro; de Oliveira, Fernando A. N.

2015-02-01

In this work we have studied the mineral dawsonite by using a combination of scanning electron microscopy with EDS and vibrational spectroscopy. Single crystals show an acicular habitus forming aggregates with a rosette shape. The chemical analysis shows a phase composed of C, Al, and Na. Two distinct Raman bands at 1091 and 1068 cm-1 are assigned to the CO32- ν1 symmetric stretching mode. Multiple bands are observed in both the Raman and infrared spectra in the antisymmetric stretching and bending regions showing that the symmetry of the carbonate anion is reduced and in all probability the carbonate anions are not equivalent in the dawsonite structure. Multiple OH deformation vibrations centred upon 950 cm-1 in both the Raman and infrared spectra show that the OH units in the dawsonite structure are non-equivalent. Raman bands observed at 3250, 3283 and 3295 cm-1 are assigned to OH stretching vibrations. The position of these bands indicates strong hydrogen bonding of the OH units in the dawsonite structure. The formation of the mineral dawsonite has the potential to offer a mechanism for the geosequestration of greenhouse gases.

Creating Reconfigurable Materials Using ``Colonies'' of Oscillating Polymer Gels

NASA Astrophysics Data System (ADS)

Deb, Debabrata; Dayal, Pratyush; Kuksenok, Olga; Balazs, Anna

2013-03-01

Species ranging from single-cell organisms to social insects can undergo auto-chemotaxis, where the entities move towards a chemo-attractant that they themselves emit. This mode of signaling allows the organisms to form large-scale structures. Using computational modeling, we show that millimeter-sized polymer gels can display similar auto-chemotaxis. In particular, we demonstrate that gels undergoing the self-oscillating Belousov-Zhabotinsky (BZ) reaction not only respond to a chemical signal from the surrounding solution, but also emit this signal and thus, multiple gel pieces can spontaneously self-aggregate. We focus on the collective behavior of ``colonies'' of BZ gels and show that communication between the individual pieces critically depends on all the neighboring gels. We isolate the conditions at which the BZ gels can undergo a type of self-recombining: if a larger gel is cut into distinct pieces that are moved relatively far apart, then their auto-chemotactic behavior drives them to move and autonomously recombine into a structure resembling the original, uncut sample. These findings reveal that the BZ gels can be used as autonomously moving building blocks to construct multiple structures and thus, provide a new route for creating dynamically reconfigurable materials.

Egg structure and ultrastructure of Paterdecolyus yanbarensis (Insecta, Orthoptera, Anostostomatidae, Anabropsinae).

PubMed

Mashimo, Yuta; Fukui, Makiko; Machida, Ryuichiro

2016-11-01

The egg structure of Paterdecolyus yanbarensis was examined using light, scanning electron and transmission electron microscopy. The egg surface shows a distinct honeycomb pattern formed by exochorionic ridges. Several micropyles are clustered on the ventral side of the egg. The egg membrane is composed of an exochorion penetrated with numerous aeropyles, an endochorion, and an extremely thin vitelline membrane. The endochorion is thickened at the posterior egg pole, probably associated with water absorption. A comparison of egg structure among Orthoptera revealed that the micropylar distribution pattern is conserved in Ensifera and Caelifera and might be regarded as a groundplan feature for each group; in Ensifera, multiple micropyles are clustered on the ventral side of the egg, whereas in Caelifera, micropyles are arranged circularly around the posterior pole of the egg. Copyright © 2016 Elsevier Ltd. All rights reserved.

From screen to structure with a harvestable microfluidic device.

PubMed

Stojanoff, Vivian; Jakoncic, Jean; Oren, Deena A; Nagarajan, V; Poulsen, Jens-Christian Navarro; Adams-Cioaba, Melanie A; Bergfors, Terese; Sommer, Morten O A

2011-08-01

Advances in automation have facilitated the widespread adoption of high-throughput vapour-diffusion methods for initial crystallization screening. However, for many proteins, screening thousands of crystallization conditions fails to yield crystals of sufficient quality for structural characterization. Here, the rates of crystal identification for thaumatin, catalase and myoglobin using microfluidic Crystal Former devices and sitting-drop vapour-diffusion plates are compared. It is shown that the Crystal Former results in a greater number of identified initial crystallization conditions compared with vapour diffusion. Furthermore, crystals of thaumatin and lysozyme obtained in the Crystal Former were used directly for structure determination both in situ and upon harvesting and cryocooling. On the basis of these results, a crystallization strategy is proposed that uses multiple methods with distinct kinetic trajectories through the protein phase diagram to increase the output of crystallization pipelines.

Raman and infrared spectroscopic study of kamphaugite-(Y)

NASA Astrophysics Data System (ADS)

Frost, Ray L.; López, Andrés; Scholz, Ricardo

2015-05-01

We have studied the carbonate mineral kamphaugite-(Y)(CaY(CO3)2(OH)·H2O), a mineral which contains yttrium and specific rare earth elements. Chemical analysis shows the presence of Ca, Y and C. Back scattering SEM appears to indicate a single pure phase. The vibrational spectroscopy of kamphaugite-(Y) was obtained using a combination of Raman and infrared spectroscopy. Two distinct Raman bands observed at 1078 and 1088 cm-1 provide evidence for the non-equivalence of the carbonate anion in the kamphaugite-(Y) structure. Such a concept is supported by the number of bands assigned to the carbonate antisymmetric stretching mode. Multiple bands in the ν4 region offers further support for the non-equivalence of carbonate anions in the structure. Vibrational spectroscopy enables aspects of the structure of the mineral kamphaugite-(Y) to be assessed.

Machine-Learned Data Structures of Lipid Marker Serum Concentrations in Multiple Sclerosis Patients Differ from Those in Healthy Subjects.

PubMed

Lötsch, Jörn; Thrun, Michael; Lerch, Florian; Brunkhorst, Robert; Schiffmann, Susanne; Thomas, Dominique; Tegder, Irmgard; Geisslinger, Gerd; Ultsch, Alfred

2017-06-07

Lipid metabolism has been suggested to be a major pathophysiological mechanism of multiple sclerosis (MS). With the increasing knowledge about lipid signaling, acquired data become increasingly complex making bioinformatics necessary in lipid research. We used unsupervised machine-learning to analyze lipid marker serum concentrations, pursuing the hypothesis that for the most relevant markers the emerging data structures will coincide with the diagnosis of MS. Machine learning was implemented as emergent self-organizing feature maps (ESOM) combined with the U*-matrix visualization technique. The data space consisted of serum concentrations of three main classes of lipid markers comprising eicosanoids ( d = 11 markers), ceramides ( d = 10), and lyosophosphatidic acids ( d = 6). They were analyzed in cohorts of MS patients ( n = 102) and healthy subjects ( n = 301). Clear data structures in the high-dimensional data space were observed in eicosanoid and ceramides serum concentrations whereas no clear structure could be found in lysophosphatidic acid concentrations. With ceramide concentrations, the structures that had emerged from unsupervised machine-learning almost completely overlapped with the known grouping of MS patients versus healthy subjects. This was only partly provided by eicosanoid serum concentrations. Thus, unsupervised machine-learning identified distinct data structures of bioactive lipid serum concentrations. These structures could be superimposed with the known grouping of MS patients versus healthy subjects, which was almost completely possible with ceramides. Therefore, based on the present analysis, ceramides are first-line candidates for further exploration as drug-gable targets or biomarkers in MS.

Related B cell clones populate the meninges and parenchyma of patients with multiple sclerosis

PubMed Central

Lovato, Laura; Willis, Simon N.; Rodig, Scott J.; Caron, Tyler; Almendinger, Stefany E.; Howell, Owain W.; Reynolds, Richard; Hafler, David A.

2011-01-01

In the central nervous system of patients with multiple sclerosis, B cell aggregates populate the meninges, raising the central question as to whether these structures relate to the B cell infiltrates found in parenchymal lesions or instead, represent a separate central nervous system immune compartment. We characterized the repertoires derived from meningeal B cell aggregates and the corresponding parenchymal infiltrates from brain tissue derived primarily from patients with progressive multiple sclerosis. The majority of expanded antigen-experienced B cell clones derived from meningeal aggregates were also present in the parenchyma. We extended this investigation to include 20 grey matter specimens containing meninges, 26 inflammatory plaques, 19 areas of normal appearing white matter and cerebral spinal fluid. Analysis of 1833 B cell receptor heavy chain variable region sequences demonstrated that antigen-experienced clones were consistently shared among these distinct compartments. This study establishes a relationship between extraparenchymal lymphoid tissue and parenchymal infiltrates and defines the arrangement of B cell clones that populate the central nervous system of patients with multiple sclerosis. PMID:21216828

Related B cell clones populate the meninges and parenchyma of patients with multiple sclerosis.

PubMed

Lovato, Laura; Willis, Simon N; Rodig, Scott J; Caron, Tyler; Almendinger, Stefany E; Howell, Owain W; Reynolds, Richard; O'Connor, Kevin C; Hafler, David A

2011-02-01

In the central nervous system of patients with multiple sclerosis, B cell aggregates populate the meninges, raising the central question as to whether these structures relate to the B cell infiltrates found in parenchymal lesions or instead, represent a separate central nervous system immune compartment. We characterized the repertoires derived from meningeal B cell aggregates and the corresponding parenchymal infiltrates from brain tissue derived primarily from patients with progressive multiple sclerosis. The majority of expanded antigen-experienced B cell clones derived from meningeal aggregates were also present in the parenchyma. We extended this investigation to include 20 grey matter specimens containing meninges, 26 inflammatory plaques, 19 areas of normal appearing white matter and cerebral spinal fluid. Analysis of 1833 B cell receptor heavy chain variable region sequences demonstrated that antigen-experienced clones were consistently shared among these distinct compartments. This study establishes a relationship between extraparenchymal lymphoid tissue and parenchymal infiltrates and defines the arrangement of B cell clones that populate the central nervous system of patients with multiple sclerosis.

Clonal Evaluation of Prostate Cancer by ERG/SPINK1 Status to Improve Prognosis Prediction

DTIC Science & Technology

2017-12-01

meaning that most men with prostate cancer have multiple, genetically distinct cancers. Pathologists cannot assess clonality by routine microscopic...Hence, in this proposal we utilized dual ERG/SPINK1 immunohistochemistry (IHC)—as a readout of clonal, mutually exclusive molecular subtypes—to assess...multiclonal (also referred to as multifocal), meaning that more than 80% of men with prostate cancer actually have multiple, genetically distinct

Immersion in altered experience: An investigation of the relationship between absorption and psychopathology

PubMed Central

Rosen, Cherise; Jones, Nev; Chase, Kayla A.; Melbourne, Jennifer K.; Grossman, Linda S.; Sharma, Rajiv P.

2017-01-01

Understanding alterations in perceptual experiences as a component of the basic symptom structure of psychosis may improve early detection and the identification of subtle shifts that can precede symptom exacerbation. We explored the phenomenological construct of absorption and psychotic experiences in both clinical (bipolar psychosis and schizophrenia spectrum) and non-clinical participants. Participants with psychosis endorsed significantly higher absorption compared to the non-clinical group. Absorption was positively correlated with all types of hallucinations and multiple types of delusions. The analysis yielded two distinct cluster groups that demarcated a distinction along the continuum of self-disturbance: on characterized by attenuated ego boundaries and the other stable ego boundaries. The study suggests that absorption is a potentially important but under-researched component of psychosis that overlaps with, but is not identical to the more heavily theorized constructs of aberrant salience and hyperreflexivity. PMID:28219788

Cornelia de Lange syndrome: a case study.

PubMed

Kalal, Goud Iravathy; Raina, Vimarsh P; Nayak, Veerabhadra S; Teotia, Pooja; Gupta, Bhushan V

2009-02-01

Cornelia de Lange syndrome (CDLS) is a relatively common multiple congenital anomaly/mental retardation disorder with an unknown genetic and molecular pathogenesis. The essential features of this developmental malformation syndrome are retardation in growth, developmental delay, various structural limb abnormalities, and distinctive facial features. Most cases are sporadic and are thought to result from a new dominant mutation. Consequently, hypotheses regarding the pathogenetic mechanisms underlying the two distinct phenotypes, classic and mild, are purely speculative. The recent discovery of molecular techniques and identification of the NIPBL gene has allowed etiologic diagnosis of this disorder. In this article, we describe a patient with CDLS in whom conventional cytogenetics, fluorescence in situ hybridization, and NIPBL gene mutation analysis determined an etiologic diagnosis, providing precise genetic counseling and facilitated the family to make an evidence-based decision for conception and also alleviated the extreme degree of anxiety associated with the thought of having a second child in this set of circumstances.

Hedging Your Bets by Learning Reward Correlations in the Human Brain

PubMed Central

Wunderlich, Klaus; Symmonds, Mkael; Bossaerts, Peter; Dolan, Raymond J.

2011-01-01

Summary Human subjects are proficient at tracking the mean and variance of rewards and updating these via prediction errors. Here, we addressed whether humans can also learn about higher-order relationships between distinct environmental outcomes, a defining ecological feature of contexts where multiple sources of rewards are available. By manipulating the degree to which distinct outcomes are correlated, we show that subjects implemented an explicit model-based strategy to learn the associated outcome correlations and were adept in using that information to dynamically adjust their choices in a task that required a minimization of outcome variance. Importantly, the experimentally generated outcome correlations were explicitly represented neuronally in right midinsula with a learning prediction error signal expressed in rostral anterior cingulate cortex. Thus, our data show that the human brain represents higher-order correlation structures between rewards, a core adaptive ability whose immediate benefit is optimized sampling. PMID:21943609

Discrete but variable structure of animal societies leads to the false perception of a social continuum

PubMed Central

Rubenstein, Dustin R.; Botero, Carlos A.; Lacey, Eileen A.

2016-01-01

Animal societies are typically divided into those in which reproduction within a group is monopolized by a single female versus those in which it is shared among multiple females. It remains controversial, however, whether these two forms of social structure represent distinct evolutionary outcomes or endpoints along a continuum of reproductive options. To address this issue and to determine whether vertebrates and insects exhibit the same patterns of variation in social structure, we examined the demographic and reproductive structures of 293 species of wasps, ants, birds and mammals. Using phylogenetically informed comparative analyses, we found strong evidence indicating that not all reproductive arrangements within social groups are viable in nature and that in societies with multiple reproductives, selection favours instead taxon-specific patterns of decrease in the proportion of breeders as a function of group size. These outcomes suggest that the selective routes to sociality differ depending upon whether monopolization of reproduction by one individual is possible and that variation within and among taxonomic groups may lead to the false perception of a continuum of social structures. Thus, the occurrence of very large societies may require either complete reproductive monopolization (monogyny/singular breeding) or the maintenance of a taxon-specific range of values for the proportional decrease in the number of breeders within a group (polygyny/plural breeding), both of which may reduce reproductive conflict among females. PMID:27293796

Discrete but variable structure of animal societies leads to the false perception of a social continuum.

PubMed

Rubenstein, Dustin R; Botero, Carlos A; Lacey, Eileen A

2016-05-01

Animal societies are typically divided into those in which reproduction within a group is monopolized by a single female versus those in which it is shared among multiple females. It remains controversial, however, whether these two forms of social structure represent distinct evolutionary outcomes or endpoints along a continuum of reproductive options. To address this issue and to determine whether vertebrates and insects exhibit the same patterns of variation in social structure, we examined the demographic and reproductive structures of 293 species of wasps, ants, birds and mammals. Using phylogenetically informed comparative analyses, we found strong evidence indicating that not all reproductive arrangements within social groups are viable in nature and that in societies with multiple reproductives, selection favours instead taxon-specific patterns of decrease in the proportion of breeders as a function of group size. These outcomes suggest that the selective routes to sociality differ depending upon whether monopolization of reproduction by one individual is possible and that variation within and among taxonomic groups may lead to the false perception of a continuum of social structures. Thus, the occurrence of very large societies may require either complete reproductive monopolization (monogyny/singular breeding) or the maintenance of a taxon-specific range of values for the proportional decrease in the number of breeders within a group (polygyny/plural breeding), both of which may reduce reproductive conflict among females.

Representing Heterogeneity in Structural Relationships Among Multiple Choice Variables Using a Latent Segmentation Approach

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

Garikapati, Venu; Astroza, Sebastian; Pendyala, Ram M.

Travel model systems often adopt a single decision structure that links several activity-travel choices together. The single decision structure is then used to predict activity-travel choices, with those downstream in the decision-making chain influenced by those upstream in the sequence. The adoption of a singular sequential causal structure to depict relationships among activity-travel choices in travel demand model systems ignores the possibility that some choices are made jointly as a bundle as well as the possible presence of structural heterogeneity in the population with respect to decision-making processes. As different segments in the population may adopt and follow different causalmore » decision-making mechanisms when making selected choices jointly, it would be of value to develop simultaneous equations model systems relating multiple endogenous choice variables that are able to identify population subgroups following alternative causal decision structures. Because the segments are not known a priori, they are considered latent and determined endogenously within a joint modeling framework proposed in this paper. The methodology is applied to a national mobility survey data set to identify population segments that follow different causal structures relating residential location choice, vehicle ownership, and car-share and mobility service usage. It is found that the model revealing three distinct latent segments best describes the data, confirming the efficacy of the modeling approach and the existence of structural heterogeneity in decision-making in the population. Future versions of activity-travel model systems should strive to incorporate such structural heterogeneity to better reflect varying decision processes across population subgroups.« less

Tensor Analysis Reveals Distinct Population Structure that Parallels the Different Computational Roles of Areas M1 and V1

PubMed Central

Ryu, Stephen I.; Shenoy, Krishna V.; Cunningham, John P.; Churchland, Mark M.

2016-01-01

Cortical firing rates frequently display elaborate and heterogeneous temporal structure. One often wishes to compute quantitative summaries of such structure—a basic example is the frequency spectrum—and compare with model-based predictions. The advent of large-scale population recordings affords the opportunity to do so in new ways, with the hope of distinguishing between potential explanations for why responses vary with time. We introduce a method that assesses a basic but previously unexplored form of population-level structure: when data contain responses across multiple neurons, conditions, and times, they are naturally expressed as a third-order tensor. We examined tensor structure for multiple datasets from primary visual cortex (V1) and primary motor cortex (M1). All V1 datasets were ‘simplest’ (there were relatively few degrees of freedom) along the neuron mode, while all M1 datasets were simplest along the condition mode. These differences could not be inferred from surface-level response features. Formal considerations suggest why tensor structure might differ across modes. For idealized linear models, structure is simplest across the neuron mode when responses reflect external variables, and simplest across the condition mode when responses reflect population dynamics. This same pattern was present for existing models that seek to explain motor cortex responses. Critically, only dynamical models displayed tensor structure that agreed with the empirical M1 data. These results illustrate that tensor structure is a basic feature of the data. For M1 the tensor structure was compatible with only a subset of existing models. PMID:27814353

Population Structure of Two Rabies Hosts Relative to the Known Distribution of Rabies Virus Variants in Alaska

PubMed Central

Goldsmith, Elizabeth W.; Renshaw, Benjamin; Clement, Christopher J.; Himschoot, Elizabeth A.; Hundertmark, Kris J.; Hueffer, Karsten

2015-01-01

For pathogens that infect multiple species the distinction between reservoir hosts and spillover hosts is often difficult. In Alaska, three variants of the arctic rabies virus exist with distinct spatial distributions. We test the hypothesis that rabies virus variant distribution corresponds to the population structure of the primary rabies hosts in Alaska, arctic foxes (Vulpes lagopus) and red foxes (V. vulpes) in order to possibly distinguish reservoir and spill over hosts. We used mitochondrial DNA (mtDNA) sequence and nine microsatellites to assess population structure in those two species. mtDNA structure did not correspond to rabies virus variant structure in either species. Microsatellite analyses gave varying results. Bayesian clustering found 2 groups of arctic foxes in the coastal tundra region, but for red foxes it identified tundra and boreal types. Spatial Bayesian clustering and spatial principal components analysis identified 3 and 4 groups of arctic foxes, respectively, closely matching the distribution of rabies virus variants in the state. Red foxes, conversely, showed eight clusters comprising 2 regions (boreal and tundra) with much admixture. These results run contrary to previous beliefs that arctic fox show no fine-scale spatial population structure. While we cannot rule out that the red fox is part of the maintenance host community for rabies in Alaska, the distribution of virus variants appears to be driven primarily by the artic fox Therefore we show that host population genetics can be utilized to distinguish between maintenance and spillover hosts when used in conjunction with other approaches. PMID:26661691

Population structure of two rabies hosts relative to the known distribution of rabies virus variants in Alaska.

PubMed

Goldsmith, Elizabeth W; Renshaw, Benjamin; Clement, Christopher J; Himschoot, Elizabeth A; Hundertmark, Kris J; Hueffer, Karsten

2016-02-01

For pathogens that infect multiple species, the distinction between reservoir hosts and spillover hosts is often difficult. In Alaska, three variants of the arctic rabies virus exist with distinct spatial distributions. We tested the hypothesis that rabies virus variant distribution corresponds to the population structure of the primary rabies hosts in Alaska, arctic foxes (Vulpes lagopus) and red foxes (Vulpes vulpes) to possibly distinguish reservoir and spillover hosts. We used mitochondrial DNA (mtDNA) sequence and nine microsatellites to assess population structure in those two species. mtDNA structure did not correspond to rabies virus variant structure in either species. Microsatellite analyses gave varying results. Bayesian clustering found two groups of arctic foxes in the coastal tundra region, but for red foxes it identified tundra and boreal types. Spatial Bayesian clustering and spatial principal components analysis identified 3 and 4 groups of arctic foxes, respectively, closely matching the distribution of rabies virus variants in the state. Red foxes, conversely, showed eight clusters comprising two regions (boreal and tundra) with much admixture. These results run contrary to previous beliefs that arctic fox show no fine-scale spatial population structure. While we cannot rule out that the red fox is part of the maintenance host community for rabies in Alaska, the distribution of virus variants appears to be driven primarily by the arctic fox. Therefore, we show that host population genetics can be utilized to distinguish between maintenance and spillover hosts when used in conjunction with other approaches. © 2015 John Wiley & Sons Ltd.

Temporal Dependency and the Structure of Early Looking.

PubMed

Messinger, Daniel S; Mattson, Whitney I; Todd, James Torrence; Gangi, Devon N; Myers, Nicholas D; Bahrick, Lorraine E

2017-01-01

Although looking time is used to assess infant perceptual and cognitive processing, little is known about the temporal structure of infant looking. To shed light on this temporal structure, 127 three-month-olds were assessed in an infant-controlled habituation procedure and presented with a pre-recorded display of a woman addressing the infant using infant-directed speech. Previous individual look durations positively predicted subsequent look durations over a six look window, suggesting a temporal dependency between successive infant looks. The previous look duration continued to predict the subsequent look duration after accounting for habituation-linked declines in look duration, and when looks were separated by an inter-trial interval in which no stimulus was displayed. Individual differences in temporal dependency, the strength of associations between consecutive look durations, are distinct from individual differences in mean infant look duration. Nevertheless, infants with stronger temporal dependency had briefer mean look durations, a potential index of stimulus processing. Temporal dependency was evident not only between individual infant looks but between the durations of successive habituation trials (total looking within a trial). Finally, temporal dependency was evident in associations between the last look at the habituation stimulus and the first look at a novel test stimulus. Thus temporal dependency was evident across multiple timescales (individual looks and trials comprised of multiple individual looks) and persisted across conditions including brief periods of no stimulus presentation and changes from a familiar to novel stimulus. Associations between consecutive look durations over multiple timescales and stimuli suggest a temporal structure of infant attention that has been largely ignored in previous work on infant looking.

Temporal Dependency and the Structure of Early Looking

PubMed Central

Messinger, Daniel S.; Mattson, Whitney I.; Todd, James Torrence; Gangi, Devon N.; Myers, Nicholas D.; Bahrick, Lorraine E.

2017-01-01

Although looking time is used to assess infant perceptual and cognitive processing, little is known about the temporal structure of infant looking. To shed light on this temporal structure, 127 three-month-olds were assessed in an infant-controlled habituation procedure and presented with a pre-recorded display of a woman addressing the infant using infant-directed speech. Previous individual look durations positively predicted subsequent look durations over a six look window, suggesting a temporal dependency between successive infant looks. The previous look duration continued to predict the subsequent look duration after accounting for habituation-linked declines in look duration, and when looks were separated by an inter-trial interval in which no stimulus was displayed. Individual differences in temporal dependency, the strength of associations between consecutive look durations, are distinct from individual differences in mean infant look duration. Nevertheless, infants with stronger temporal dependency had briefer mean look durations, a potential index of stimulus processing. Temporal dependency was evident not only between individual infant looks but between the durations of successive habituation trials (total looking within a trial). Finally, temporal dependency was evident in associations between the last look at the habituation stimulus and the first look at a novel test stimulus. Thus temporal dependency was evident across multiple timescales (individual looks and trials comprised of multiple individual looks) and persisted across conditions including brief periods of no stimulus presentation and changes from a familiar to novel stimulus. Associations between consecutive look durations over multiple timescales and stimuli suggest a temporal structure of infant attention that has been largely ignored in previous work on infant looking. PMID:28076362

R3D-2-MSA: the RNA 3D structure-to-multiple sequence alignment server.

PubMed

Cannone, Jamie J; Sweeney, Blake A; Petrov, Anton I; Gutell, Robin R; Zirbel, Craig L; Leontis, Neocles

2015-07-01

The RNA 3D Structure-to-Multiple Sequence Alignment Server (R3D-2-MSA) is a new web service that seamlessly links RNA three-dimensional (3D) structures to high-quality RNA multiple sequence alignments (MSAs) from diverse biological sources. In this first release, R3D-2-MSA provides manual and programmatic access to curated, representative ribosomal RNA sequence alignments from bacterial, archaeal, eukaryal and organellar ribosomes, using nucleotide numbers from representative atomic-resolution 3D structures. A web-based front end is available for manual entry and an Application Program Interface for programmatic access. Users can specify up to five ranges of nucleotides and 50 nucleotide positions per range. The R3D-2-MSA server maps these ranges to the appropriate columns of the corresponding MSA and returns the contents of the columns, either for display in a web browser or in JSON format for subsequent programmatic use. The browser output page provides a 3D interactive display of the query, a full list of sequence variants with taxonomic information and a statistical summary of distinct sequence variants found. The output can be filtered and sorted in the browser. Previous user queries can be viewed at any time by resubmitting the output URL, which encodes the search and re-generates the results. The service is freely available with no login requirement at http://rna.bgsu.edu/r3d-2-msa. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

The Interpretation Of Multiple Foliations In Metapelites: An Example From NW-Namibia

NASA Astrophysics Data System (ADS)

Passchier, C. W.

2014-12-01

Foliations in metapelites belong to the most important tools in structural geology to reconstruct deformation history and kinematics. Since foliations are easily developed and are hard to destroy, multiple foliations, associated with other structures such as folds and boudins, serve as a basis in reconstructing the tectonic history of all metamorphic terrains. Traditionally, such reconstructions assume regionally homogeneous tectonic effects producing distinct generations of structures, which are then labelled D1, D2, D3 etc. The Goantagab Domain in NW Namibia consists of Neoproterozoic pelitic and psammitic metaturbidites with only minor changes in facies, exposed over an area of 80x40km. The rocks were deformed in a transpressive Neoproterozoic to Cambrian tectonic event during the amalgamation of Gondwanaland. Five overprinting foliations can be recognised in the area, but only three are recognisable at any location and no foliation extends over the entire area. Apparently, small variations in kinematic vorticity and other kinematic parameters and in orientation of incremental strain axes lead to local foliation development and to gradients in foliation style. The similarity in field and microstructure of the different foliations, and gradations in their development make a classical approach using D1-D2-D3 labelling problematic. Since the fieldwork area is very well exposed, it is possible to determine which factors lead to local development and destruction of foliations during ongoing ductile deformation. Detailed analysis of the local foliation architecture and history is used to explore new methods in structural geology to handle complex multiple foliations in metamorphic terrains

Reach-scale channel sensitivity to multiple human activities and natural events: Lower Santa Clara River, California, USA

NASA Astrophysics Data System (ADS)

Downs, Peter W.; Dusterhoff, Scott R.; Sears, William A.

2013-05-01

Understanding the cumulative impact of natural and human influences on the sensitivity of channel morphodynamics, a relative measure between the drivers for change and the magnitude of channel response, requires an approach that accommodates spatial and temporal variability in the suite of primary stressors. Multiple historical data sources were assembled to provide a reach-scale analysis of the lower Santa Clara River (LSCR) in Ventura County, California, USA. Sediment supply is naturally high due to tectonic activity, earthquake-generated landslides, wildfires, and high magnitude flow events during El Niño years. Somewhat typically for the region, the catchment has been subject to four reasonably distinct land use and resource management combinations since European-American settlement. When combined with analysis of channel morphological response (quantifiable since ca. 1930), reach-scale and temporal differences in channel sensitivity become apparent. Downstream reaches have incised on average 2.4 m and become narrower by almost 50% with changes focused in a period of highly sensitive response after about 1950 followed by forced insensitivity caused by structural flood embankments and a significant grade control structure. In contrast, the middle reaches have been responsive but are morphologically resilient, and the upstream reaches show a mildly sensitive aggradational trend. Superimposing the natural and human drivers for change reveals that large scale stressors (related to ranching and irrigation) have been replaced over time by a suite of stressors operating at multiple spatial scales. Lower reaches have been sensitive primarily to 'local' scale impacts (urban growth, flood control, and aggregate mining) whereas, upstream, catchment-scale influences still prevail (including flow regulation and climate-driven sediment supply factors). These factors illustrate the complexity inherent to cumulative impact assessment in fluvial systems, provide evidence for a distinct Anthropocene fluvial response, and underpin the enormity of the challenge faced in trying to sustainably manage and restore rivers.

Disorder in convergent floral nanostructures enhances signalling to bees

NASA Astrophysics Data System (ADS)

Moyroud, Edwige; Wenzel, Tobias; Middleton, Rox; Rudall, Paula J.; Banks, Hannah; Reed, Alison; Mellers, Greg; Killoran, Patrick; Westwood, M. Murphy; Steiner, Ullrich; Vignolini, Silvia; Glover, Beverley J.

2017-10-01

Diverse forms of nanoscale architecture generate structural colour and perform signalling functions within and between species. Structural colour is the result of the interference of light from approximately regular periodic structures; some structural disorder is, however, inevitable in biological organisms. Is this disorder functional and subject to evolutionary selection, or is it simply an unavoidable outcome of biological developmental processes? Here we show that disordered nanostructures enable flowers to produce visual signals that are salient to bees. These disordered nanostructures (identified in most major lineages of angiosperms) have distinct anatomies but convergent optical properties; they all produce angle-dependent scattered light, predominantly at short wavelengths (ultraviolet and blue). We manufactured artificial flowers with nanoscale structures that possessed tailored levels of disorder in order to investigate how foraging bumblebees respond to this optical effect. We conclude that floral nanostructures have evolved, on multiple independent occasions, an effective degree of relative spatial disorder that generates a photonic signature that is highly salient to insect pollinators.

Computational Modeling of Airway and Pulmonary Vascular Structure and Function: Development of a “Lung Physiome”

PubMed Central

Tawhai, M. H.; Clark, A. R.; Donovan, G. M.; Burrowes, K. S.

2011-01-01

Computational models of lung structure and function necessarily span multiple spatial and temporal scales, i.e., dynamic molecular interactions give rise to whole organ function, and the link between these scales cannot be fully understood if only molecular or organ-level function is considered. Here, we review progress in constructing multiscale finite element models of lung structure and function that are aimed at providing a computational framework for bridging the spatial scales from molecular to whole organ. These include structural models of the intact lung, embedded models of the pulmonary airways that couple to model lung tissue, and models of the pulmonary vasculature that account for distinct structural differences at the extra- and intra-acinar levels. Biophysically based functional models for tissue deformation, pulmonary blood flow, and airway bronchoconstriction are also described. The development of these advanced multiscale models has led to a better understanding of complex physiological mechanisms that govern regional lung perfusion and emergent heterogeneity during bronchoconstriction. PMID:22011236

Effect of posttranslational modifications on enzyme function and assembly.

PubMed

Ryšlavá, Helena; Doubnerová, Veronika; Kavan, Daniel; Vaněk, Ondřej

2013-10-30

The detailed examination of enzyme molecules by mass spectrometry and other techniques continues to identify hundreds of distinct PTMs. Recently, global analyses of enzymes using methods of contemporary proteomics revealed widespread distribution of PTMs on many key enzymes distributed in all cellular compartments. Critically, patterns of multiple enzymatic and nonenzymatic PTMs within a single enzyme are now functionally evaluated providing a holistic picture of a macromolecule interacting with low molecular mass compounds, some of them being substrates, enzyme regulators, or activated precursors for enzymatic and nonenzymatic PTMs. Multiple PTMs within a single enzyme molecule and their mutual interplays are critical for the regulation of catalytic activity. Full understanding of this regulation will require detailed structural investigation of enzymes, their structural analogs, and their complexes. Further, proteomics is now integrated with molecular genetics, transcriptomics, and other areas leading to systems biology strategies. These allow the functional interrogation of complex enzymatic networks in their natural environment. In the future, one might envisage the use of robust high throughput analytical techniques that will be able to detect multiple PTMs on a global scale of individual proteomes from a number of carefully selected cells and cellular compartments. This article is part of a Special Issue entitled: Posttranslational Protein modifications in biology and Medicine. Copyright © 2013 Elsevier B.V. All rights reserved.

Emitter and absorber assembly for multiple self-dual operation and directional transparency

NASA Astrophysics Data System (ADS)

Kalozoumis, P. A.; Morfonios, C. V.; Kodaxis, G.; Diakonos, F. K.; Schmelcher, P.

2017-03-01

We demonstrate how to systematically design wave scattering systems with simultaneous coherent perfect absorbing and lasing operation at multiple and prescribed frequencies. The approach is based on the recursive assembly of non-Hermitian emitter and absorber units into self-dual emitter-absorber trimers at different composition levels, exploiting the simple structure of the corresponding transfer matrices. In particular, lifting the restriction to parity-time-symmetric setups enables the realization of emitter and absorber action at distinct frequencies and provides flexibility with respect to the choice of realistic parameters. We further show how the same assembled scatterers can be rearranged to produce unidirectional and bidirectional transparency at the selected frequencies. With the design procedure being generically applicable to wave scattering in single-channel settings, we demonstrate it with concrete examples of photonic multilayer setups.

Genetically distinct leukemic stem cells in human CD34− acute myeloid leukemia are arrested at a hemopoietic precursor-like stage

PubMed Central

Quek, Lynn; Garnett, Catherine; Karamitros, Dimitris; Stoilova, Bilyana; Doondeea, Jessica; Kennedy, Alison; Metzner, Marlen; Ivey, Adam; Sternberg, Alexander; Hunter, Hannah; Price, Andrew; Virgo, Paul; Grimwade, David; Freeman, Sylvie; Russell, Nigel; Mead, Adam

2016-01-01

Our understanding of the perturbation of normal cellular differentiation hierarchies to create tumor-propagating stem cell populations is incomplete. In human acute myeloid leukemia (AML), current models suggest transformation creates leukemic stem cell (LSC) populations arrested at a progenitor-like stage expressing cell surface CD34. We show that in ∼25% of AML, with a distinct genetic mutation pattern where >98% of cells are CD34−, there are multiple, nonhierarchically arranged CD34+ and CD34− LSC populations. Within CD34− and CD34+ LSC–containing populations, LSC frequencies are similar; there are shared clonal structures and near-identical transcriptional signatures. CD34− LSCs have disordered global transcription profiles, but these profiles are enriched for transcriptional signatures of normal CD34− mature granulocyte–macrophage precursors, downstream of progenitors. But unlike mature precursors, LSCs express multiple normal stem cell transcriptional regulators previously implicated in LSC function. This suggests a new refined model of the relationship between LSCs and normal hemopoiesis in which the nature of genetic/epigenetic changes determines the disordered transcriptional program, resulting in LSC differentiation arrest at stages that are most like either progenitor or precursor stages of hemopoiesis. PMID:27377587

Hierarchical Feedback Modules and Reaction Hubs in Cell Signaling Networks

PubMed Central

Xu, Jianfeng; Lan, Yueheng

2015-01-01

Despite much effort, identification of modular structures and study of their organizing and functional roles remain a formidable challenge in molecular systems biology, which, however, is essential in reaching a systematic understanding of large-scale cell regulation networks and hence gaining capacity of exerting effective interference to cell activity. Combining graph theoretic methods with available dynamics information, we successfully retrieved multiple feedback modules of three important signaling networks. These feedbacks are structurally arranged in a hierarchical way and dynamically produce layered temporal profiles of output signals. We found that global and local feedbacks act in very different ways and on distinct features of the information flow conveyed by signal transduction but work highly coordinately to implement specific biological functions. The redundancy embodied with multiple signal-relaying channels and feedback controls bestow great robustness and the reaction hubs seated at junctions of different paths announce their paramount importance through exquisite parameter management. The current investigation reveals intriguing general features of the organization of cell signaling networks and their relevance to biological function, which may find interesting applications in analysis, design and control of bio-networks. PMID:25951347

Coaxial GaAs-AlGaAs core-multishell nanowire lasers with epitaxial gain control

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

Stettner, T., E-mail: Thomas.Stettner@wsi.tum.de, E-mail: Gregor.Koblmueller@wsi.tum.de, E-mail: Jonathan.Finley@wsi.tum.de; Zimmermann, P.; Loitsch, B.

2016-01-04

We demonstrate the growth and single-mode lasing operation of GaAs-AlGaAs core-multishell nanowires (NW) with radial single and multiple GaAs quantum wells (QWs) as active gain media. When subject to optical pumping lasing emission with distinct s-shaped input-output characteristics, linewidth narrowing and emission energies associated with the confined QWs are observed. Comparing the low temperature performance of QW NW laser structures having 7 coaxial QWs with a nominally identical structure having only a single QW shows that the threshold power density reduces several-fold, down to values as low as ∼2.4 kW/cm{sup 2} for the multiple QW NW laser. This confirms that themore » individual radial QWs are electronically weakly coupled and that epitaxial design can be used to optimize the gain characteristics of the devices. Temperature-dependent investigations show that lasing prevails up to 300 K, opening promising new avenues for efficient III–V semiconductor NW lasers with embedded low-dimensional gain media.« less

Leaf-FISH: Microscale Imaging of Bacterial Taxa on Phyllosphere

PubMed Central

Peredo, Elena L.; Simmons, Sheri L.

2018-01-01

Molecular methods for microbial community characterization have uncovered environmental and plant-associated factors shaping phyllosphere communities. Variables undetectable using bulk methods can play an important role in shaping plant-microbe interactions. Microscale analysis of bacterial dynamics in the phyllosphere requires imaging techniques specially adapted to the high autoflouresence and 3-D structure of the leaf surface. We present an easily-transferable method (Leaf-FISH) to generate high-resolution tridimensional images of leaf surfaces that allows simultaneous visualization of multiple bacterial taxa in a structurally informed context, using taxon-specific fluorescently labeled oligonucleotide probes. Using a combination of leaf pretreatments coupled with spectral imaging confocal microscopy, we demonstrate the successful imaging bacterial taxa at the genus level on cuticular and subcuticular leaf areas. Our results confirm that different bacterial species, including closely related isolates, colonize distinct microhabitats in the leaf. We demonstrate that highly related Methylobacterium species have distinct colonization patterns that could not be predicted by shared physiological traits, such as carbon source requirements or phytohormone production. High-resolution characterization of microbial colonization patterns is critical for an accurate understanding of microbe-microbe and microbe-plant interactions, and for the development of foliar bacteria as plant-protective agents. PMID:29375531

Structures of Human CCL18, CCL3, and CCL4 Reveal Molecular Determinants for Quaternary Structures and Sensitivity to Insulin-Degrading Enzyme

DOE PAGES

Liang, Wenguang G.; Ren, Min; Zhao, Fan; ...

2015-01-27

CC chemokine ligands (CCL) are 8-14 kDa signaling proteins involved in diverse immune functions. While CCLs share similar tertiary structures, oligomerization produces highly diverse quaternary structures that protect chemokines from proteolytic degradation and modulate their functions. CCL18 is closely related to CCL3 and CCL4 with respect to both protein sequence and genomic location, yet CCL18 has distinct biochemical and biophysical properties. Here in this paper, we report a crystal structure of human CCL18 and its oligomerization states in solution based on crystallographic and small angle X-ray scattering (SAXS) analyses. Our data shows that CCL18 adopts an α-helical conformation at itsmore » N-terminus that weakens its dimerization, explaining CCL18’s preference for the monomeric state. Multiple contacts between monomers allow CCL18 to reversibly form a unique open-ended oligomer different from those of CCL3, CCL4, and CCL5. Furthermore, these differences hinge on proline 8, which is conserved in CCL3 and CCL4, but is replaced by lysine in human CCL18. Our structural analyses suggest that a proline 8 to alanine mutation stabilizes a type I β-turn at the N-terminus of CCL4 to prevent dimerization but prevents dimers from making key contacts with each other in CCL3. Thus, the P8A mutation induces depolymerization of CCL3 and CCL4 by distinct mechanisms. Finally, we used structural, biochemical, and functional analyses to unravel why insulin-degrading enzyme (IDE) degrades CCL3 and CCL4 but not CCL18. Lastly, our results elucidate the molecular basis for the oligomerization of three closely related CC chemokines and suggest how oligomerization shapes CCL chemokine function.« less

Structures of human CCL18, CCL3, and CCL4 reveal molecular determinants for quaternary structures and sensitivity to insulin-degrading enzyme.

PubMed

Liang, Wenguang G; Ren, Min; Zhao, Fan; Tang, Wei-Jen

2015-03-27

CC chemokine ligands (CCLs) are 8- to 14-kDa signaling proteins involved in diverse immune functions. While CCLs share similar tertiary structures, oligomerization produces highly diverse quaternary structures that protect chemokines from proteolytic degradation and modulate their functions. CCL18 is closely related to CCL3 and CCL4 with respect to both protein sequence and genomic location, yet CCL18 has distinct biochemical and biophysical properties. Here, we report a crystal structure of human CCL18 and its oligomerization states in solution based on crystallographic and small-angle X-ray scattering analyses. Our data show that CCL18 adopts an α-helical conformation at its N-terminus that weakens its dimerization, explaining CCL18's preference for the monomeric state. Multiple contacts between monomers allow CCL18 to reversibly form a unique open-ended oligomer different from those of CCL3, CCL4, and CCL5. Furthermore, these differences hinge on proline 8, which is conserved in CCL3 and CCL4 but is replaced by lysine in human CCL18. Our structural analyses suggest that a mutation of proline 8 to alanine stabilizes a type 1 β-turn at the N-terminus of CCL4 to prevent dimerization but prevents dimers from making key contacts with each other in CCL3. Thus, the P8A mutation induces depolymerization of CCL3 and CCL4 by distinct mechanisms. Finally, we used structural, biochemical, and functional analyses to unravel why insulin-degrading enzyme degrades CCL3 and CCL4 but not CCL18. Our results elucidate the molecular basis for the oligomerization of three closely related CC chemokines and suggest how oligomerization shapes CCL chemokine function. Copyright © 2015 Elsevier Ltd. All rights reserved.

Information processing in the primate visual system - An integrated systems perspective

NASA Technical Reports Server (NTRS)

Van Essen, David C.; Anderson, Charles H.; Felleman, Daniel J.

1992-01-01

The primate visual system contains dozens of distinct areas in the cerebral cortex and several major subcortical structures. These subdivisions are extensively interconnected in a distributed hierarchical network that contains several intertwined processing streams. A number of strategies are used for efficient information processing within this hierarchy. These include linear and nonlinear filtering, passage through information bottlenecks, and coordinated use of multiple types of information. In addition, dynamic regulation of information flow within and between visual areas may provide the computational flexibility needed for the visual system to perform a broad spectrum of tasks accurately and at high resolution.

Convergent evolution of gene networks by single-gene duplications in higher eukaryotes.

PubMed

Amoutzias, Gregory D; Robertson, David L; Oliver, Stephen G; Bornberg-Bauer, Erich

2004-03-01

By combining phylogenetic, proteomic and structural information, we have elucidated the evolutionary driving forces for the gene-regulatory interaction networks of basic helix-loop-helix transcription factors. We infer that recurrent events of single-gene duplication and domain rearrangement repeatedly gave rise to distinct networks with almost identical hub-based topologies, and multiple activators and repressors. We thus provide the first empirical evidence for scale-free protein networks emerging through single-gene duplications, the dominant importance of molecular modularity in the bottom-up construction of complex biological entities, and the convergent evolution of networks.

Measuring floodplain spatial patterns using continuous surface metrics at multiple scales

USGS Publications Warehouse

Scown, Murray W.; Thoms, Martin C.; DeJager, Nathan R.

2015-01-01

Interactions between fluvial processes and floodplain ecosystems occur upon a floodplain surface that is often physically complex. Spatial patterns in floodplain topography have only recently been quantified over multiple scales, and discrepancies exist in how floodplain surfaces are perceived to be spatially organised. We measured spatial patterns in floodplain topography for pool 9 of the Upper Mississippi River, USA, using moving window analyses of eight surface metrics applied to a 1 × 1 m2 DEM over multiple scales. The metrics used were Range, SD, Skewness, Kurtosis, CV, SDCURV,Rugosity, and Vol:Area, and window sizes ranged from 10 to 1000 m in radius. Surface metric values were highly variable across the floodplain and revealed a high degree of spatial organisation in floodplain topography. Moran's I correlograms fit to the landscape of each metric at each window size revealed that patchiness existed at nearly all window sizes, but the strength and scale of patchiness changed within window size, suggesting that multiple scales of patchiness and patch structure exist in the topography of this floodplain. Scale thresholds in the spatial patterns were observed, particularly between the 50 and 100 m window sizes for all surface metrics and between the 500 and 750 m window sizes for most metrics. These threshold scales are ~ 15–20% and 150% of the main channel width (1–2% and 10–15% of the floodplain width), respectively. These thresholds may be related to structuring processes operating across distinct scale ranges. By coupling surface metrics, multi-scale analyses, and correlograms, quantifying floodplain topographic complexity is possible in ways that should assist in clarifying how floodplain ecosystems are structured.

A combined post-mortem magnetic resonance imaging and quantitative histological study of multiple sclerosis pathology

PubMed Central

Kolasinski, James; Chance, Steven A.; DeLuca, Gabriele C.; Esiri, Margaret M.; Chang, Eun-Hyuk; Palace, Jacqueline A.; McNab, Jennifer A.; Jenkinson, Mark; Miller, Karla L.; Johansen-Berg, Heidi

2012-01-01

Multiple sclerosis is a chronic inflammatory neurological condition characterized by focal and diffuse neurodegeneration and demyelination throughout the central nervous system. Factors influencing the progression of pathology are poorly understood. One hypothesis is that anatomical connectivity influences the spread of neurodegeneration. This predicts that measures of neurodegeneration will correlate most strongly between interconnected structures. However, such patterns have been difficult to quantify through post-mortem neuropathology or in vivo scanning alone. In this study, we used the complementary approaches of whole brain post-mortem magnetic resonance imaging and quantitative histology to assess patterns of multiple sclerosis pathology. Two thalamo-cortical projection systems were considered based on their distinct neuroanatomy and their documented involvement in multiple sclerosis: lateral geniculate nucleus to primary visual cortex and mediodorsal nucleus of the thalamus to prefrontal cortex. Within the anatomically distinct thalamo-cortical projection systems, magnetic resonance imaging derived cortical thickness was correlated significantly with both a measure of myelination in the connected tract and a measure of connected thalamic nucleus cell density. Such correlations did not exist between these markers of neurodegeneration across different thalamo-cortical systems. Magnetic resonance imaging lesion analysis depicted clearly demarcated subcortical lesions impinging on the white matter tracts of interest; however, quantitation of the extent of lesion-tract overlap failed to demonstrate any appreciable association with the severity of markers of diffuse pathology within each thalamo-cortical projection system. Diffusion-weighted magnetic resonance imaging metrics in both white matter tracts were correlated significantly with a histologically derived measure of tract myelination. These data demonstrate for the first time the relevance of functional anatomical connectivity to the spread of multiple sclerosis pathology in a ‘tract-specific’ pattern. Furthermore, the persisting relationship between metrics from post-mortem diffusion-weighted magnetic resonance imaging and histological measures from fixed tissue further validates the potential of imaging for future neuropathological studies. PMID:23065787

Control of hierarchical polymer mechanics with bioinspired metal-coordination dynamics

PubMed Central

Grindy, Scott C.; Learsch, Robert; Mozhdehi, Davoud; Cheng, Jing; Barrett, Devin G.; Guan, Zhibin; Messersmith, Phillip B.; Holten-Andersen, Niels

2015-01-01

In conventional polymer materials, mechanical performance is traditionally engineered via material structure, using motifs such as polymer molecular weight, polymer branching, or copolymer-block design1. Here, by means of a model system of 4-arm poly(ethylene glycol) hydrogels crosslinked with multiple, kinetically distinct dynamic metal-ligand coordinate complexes, we show that polymer materials with decoupled spatial structure and mechanical performance can be designed. By tuning the relative concentration of two types of metal-ligand crosslinks, we demonstrate control over the material’s mechanical hierarchy of energy-dissipating modes under dynamic mechanical loading, and therefore the ability to engineer a priori the viscoelastic properties of these materials by controlling the types of crosslinks rather than by modifying the polymer itself. This strategy to decouple material mechanics from structure may inform the design of soft materials for use in complex mechanical environments. PMID:26322715

Zero-index structures as an alternative platform for quantum optics

PubMed Central

Liberal, Iñigo

2017-01-01

Vacuum fluctuations are one of the most distinctive aspects of quantum optics, being the trigger of multiple nonclassical phenomena. Thus, platforms like resonant cavities and photonic crystals that enable the inhibition and manipulation of vacuum fluctuations have been key to our ability to control light–matter interactions (e.g., the decay of quantum emitters). Here, we theoretically demonstrate that vacuum fluctuations may be naturally inhibited within bodies immersed in epsilon-and-mu-near-zero (EMNZ) media, while they can also be selectively excited via bound eigenmodes. Therefore, zero-index structures are proposed as an alternative platform to manipulate the decay of quantum emitters, possibly leading to the exploration of qualitatively different dynamics. For example, a direct modulation of the vacuum Rabi frequency is obtained by deforming the EMNZ region without detuning a bound eigenmode. Ideas for the possible implementation of these concepts using synthetic implementations based on structural dispersion are also proposed. PMID:28096367

Zero-index structures as an alternative platform for quantum optics.

PubMed

Liberal, Iñigo; Engheta, Nader

2017-01-31

Vacuum fluctuations are one of the most distinctive aspects of quantum optics, being the trigger of multiple nonclassical phenomena. Thus, platforms like resonant cavities and photonic crystals that enable the inhibition and manipulation of vacuum fluctuations have been key to our ability to control light-matter interactions (e.g., the decay of quantum emitters). Here, we theoretically demonstrate that vacuum fluctuations may be naturally inhibited within bodies immersed in epsilon-and-mu-near-zero (EMNZ) media, while they can also be selectively excited via bound eigenmodes. Therefore, zero-index structures are proposed as an alternative platform to manipulate the decay of quantum emitters, possibly leading to the exploration of qualitatively different dynamics. For example, a direct modulation of the vacuum Rabi frequency is obtained by deforming the EMNZ region without detuning a bound eigenmode. Ideas for the possible implementation of these concepts using synthetic implementations based on structural dispersion are also proposed.

Topological Nodal-Net Semimetal in a Graphene Network Structure

NASA Astrophysics Data System (ADS)

Wang, Jian-Tao; Nie, Simin; Weng, Hongming; Kawazoe, Yoshiyuki; Chen, Changfeng

2018-01-01

Topological semimetals are characterized by the nodal points in their electronic structure near the Fermi level, either discrete or forming a continuous line or ring, which are responsible for exotic properties related to the topology of bulk bands. Here we identify by ab initio calculations a distinct topological semimetal that exhibits nodal nets comprising multiple interconnected nodal lines in bulk and have two coupled drumheadlike flat bands around the Fermi level on its surface. This nodal net semimetal state is proposed to be realized in a graphene network structure that can be constructed by inserting a benzene ring into each C- C bond in the bct-C4 lattice or by a crystalline modification of the (5,5) carbon nanotube. These results expand the realm of nodal manifolds in topological semimetals, offering a new platform for exploring novel physics in these fascinating materials.

Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution.

PubMed

Shen, Huaizong; Zhou, Qiang; Pan, Xiaojing; Li, Zhangqiang; Wu, Jianping; Yan, Nieng

2017-03-03

Voltage-gated sodium (Na v ) channels are responsible for the initiation and propagation of action potentials. They are associated with a variety of channelopathies and are targeted by multiple pharmaceutical drugs and natural toxins. Here, we report the cryogenic electron microscopy structure of a putative Na v channel from American cockroach (designated Na v PaS) at 3.8 angstrom resolution. The voltage-sensing domains (VSDs) of the four repeats exhibit distinct conformations. The entrance to the asymmetric selectivity filter vestibule is guarded by heavily glycosylated and disulfide bond-stabilized extracellular loops. On the cytoplasmic side, a conserved amino-terminal domain is placed below VSD I , and a carboxy-terminal domain binds to the III-IV linker. The structure of Na v PaS establishes an important foundation for understanding function and disease mechanism of Na v and related voltage-gated calcium channels. Copyright © 2017, American Association for the Advancement of Science.

Simulation studies of the fidelity of biomolecular structure ensemble recreation

NASA Astrophysics Data System (ADS)

Lätzer, Joachim; Eastwood, Michael P.; Wolynes, Peter G.

2006-12-01

We examine the ability of Bayesian methods to recreate structural ensembles for partially folded molecules from averaged data. Specifically we test the ability of various algorithms to recreate different transition state ensembles for folding proteins using a multiple replica simulation algorithm using input from "gold standard" reference ensembles that were first generated with a Gō-like Hamiltonian having nonpairwise additive terms. A set of low resolution data, which function as the "experimental" ϕ values, were first constructed from this reference ensemble. The resulting ϕ values were then treated as one would treat laboratory experimental data and were used as input in the replica reconstruction algorithm. The resulting ensembles of structures obtained by the replica algorithm were compared to the gold standard reference ensemble, from which those "data" were, in fact, obtained. It is found that for a unimodal transition state ensemble with a low barrier, the multiple replica algorithm does recreate the reference ensemble fairly successfully when no experimental error is assumed. The Kolmogorov-Smirnov test as well as principal component analysis show that the overlap of the recovered and reference ensembles is significantly enhanced when multiple replicas are used. Reduction of the multiple replica ensembles by clustering successfully yields subensembles with close similarity to the reference ensembles. On the other hand, for a high barrier transition state with two distinct transition state ensembles, the single replica algorithm only samples a few structures of one of the reference ensemble basins. This is due to the fact that the ϕ values are intrinsically ensemble averaged quantities. The replica algorithm with multiple copies does sample both reference ensemble basins. In contrast to the single replica case, the multiple replicas are constrained to reproduce the average ϕ values, but allow fluctuations in ϕ for each individual copy. These fluctuations facilitate a more faithful sampling of the reference ensemble basins. Finally, we test how robustly the reconstruction algorithm can function by introducing errors in ϕ comparable in magnitude to those suggested by some authors. In this circumstance we observe that the chances of ensemble recovery with the replica algorithm are poor using a single replica, but are improved when multiple copies are used. A multimodal transition state ensemble, however, turns out to be more sensitive to large errors in ϕ (if appropriately gauged) and attempts at successful recreation of the reference ensemble with simple replica algorithms can fall short.

Facilitating Recognition Memory: The Use of Distinctive Contexts in Study Materials and Tests.

ERIC Educational Resources Information Center

Marlin, Carol A.; And Others

The effects of distinctive background settings on children's recognition memory for subjects and objects of related sentences was examined. As a follow-up to a study by Levin, Ghatala, and Truman (1979), the effects of presenting distinctive background contexts in sentences and multiple-choice tests were separated from the effects of providing…

Short-range phenotypic divergence among genetically distinct parapatric populations of an Australian funnel-web spider.

PubMed

Wong, Mark K L; Woodman, James D; Rowell, David M

2017-07-01

Speciation involves divergence at genetic and phenotypic levels. Where substantial genetic differentiation exists among populations, examining variation in multiple phenotypic characters may elucidate the mechanisms by which divergence and speciation unfold. Previous work on the Australian funnel-web spider Atrax sutherlandi Gray (2010; Records of the Australian Museum 62 , 285-392; Mygalomorphae: Hexathelidae: Atracinae) has revealed a marked genetic structure along a 110-kilometer transect, with six genetically distinct, parapatric populations attributable to past glacial cycles. In the present study, we explore variation in three classes of phenotypic characters (metabolic rate, water loss, and morphological traits) within the context of this phylogeographic structuring. Variation in metabolic and water loss rates shows no detectable association with genetic structure; the little variation observed in these rates may be due to the spiders' behavioral adaptations (i.e., burrowing), which buffer the effects of climatic gradients across the landscape. However, of 17 morphological traits measured, 10 show significant variation among genetic populations, in a disjunct manner that is clearly not latitudinal. Moreover, patterns of variation observed for morphological traits serving different organismic functions (e.g., prey capture, burrowing, and locomotion) are dissimilar. In contrast, a previous study of an ecologically similar sympatric spider with little genetic structure indicated a strong latitudinal response in 10 traits over the same range. The congruence of morphological variation with deep phylogeographic structure in Tallaganda's A. sutherlandi populations, as well as the inconsistent patterns of variation across separate functional traits, suggest that the spiders are likely in early stages of speciation, with parapatric populations independently responding to local selective forces.

Distinct structural features of the peroxide response regulator from group A Streptococcus drive DNA binding.

PubMed

Lin, Chang Sheng-Huei; Chao, Shi-Yu; Hammel, Michal; Nix, Jay C; Tseng, Hsiao-Ling; Tsou, Chih-Cheng; Fei, Chun-Hsien; Chiou, Huo-Sheng; Jeng, U-Ser; Lin, Yee-Shin; Chuang, Woei-Jer; Wu, Jiunn-Jong; Wang, Shuying

2014-01-01

Group A streptococcus (GAS, Streptococcus pyogenes) is a strict human pathogen that causes severe, invasive diseases. GAS does not produce catalase, but has an ability to resist killing by reactive oxygen species (ROS) through novel mechanisms. The peroxide response regulator (PerR), a member of ferric uptake regulator (Fur) family, plays a key role for GAS to cope with oxidative stress by regulating the expression of multiple genes. Our previous studies have found that expression of an iron-binding protein, Dpr, is under the direct control of PerR. To elucidate the molecular interactions of PerR with its cognate promoter, we have carried out structural studies on PerR and PerR-DNA complex. By combining crystallography and small-angle X-ray scattering (SAXS), we confirmed that the determined PerR crystal structure reflects its conformation in solution. Through mutagenesis and biochemical analysis, we have identified DNA-binding residues suggesting that PerR binds to the dpr promoter at the per box through a winged-helix motif. Furthermore, we have performed SAXS analysis and resolved the molecular architecture of PerR-DNA complex, in which two 30 bp DNA fragments wrap around two PerR homodimers by interacting with the adjacent positively-charged winged-helix motifs. Overall, we provide structural insights into molecular recognition of DNA by PerR and define the hollow structural arrangement of PerR-30bpDNA complex, which displays a unique topology distinct from currently proposed DNA-binding models for Fur family regulators.

Genetic diversity and population structure of an Italian landrace of runner bean (Phaseolus coccineus L.): inferences for its safeguard and on-farm conservation.

PubMed

Mercati, F; Catarcione, G; Paolacci, A R; Abenavoli, M R; Sunseri, F; Ciaffi, M

2015-08-01

The landraces are considered important sources of valuable germplasm for breeding activities to face climatic changes as well as to satisfy the requirement of new varieties for marginal areas. Runner bean (Phaseolus coccineus L.) is one of the most cultivated Phaseolus species worldwide, but few studies have been addressed to assess the genetic diversity and structure within and among landrace populations. In the present study, 20 different populations of a runner bean landrace from Central Italy named "Fagiolone," together with 41 accessions from Italy and Mesoamerica, were evaluated by using 14 nuclear SSRs to establish its genetic structure and distinctiveness. Results indicated that "Fagiolone" landrace can be considered as a dynamic evolving open-pollinated population that shows a significant level of genetic variation, mostly detected within populations, and the presence of two main genetic groups, of which one distinguished from other Italian runner bean landraces. Results highlighted also a relevant importance of farmers' management practices able to influence the genetic structure of this landrace, in particular the seed exchanges and selection, and the past introduction in cultivation of landraces/cultivars similar to seed morphology, but genetically rather far from "Fagiolone." The most suitable on-farm strategies for seed collection, conservation and multiplication will be defined based on our results, as a model for threatened populations of other allogamous crop species. STRUCTURE and phylogenetic analyses indicated that Mesoamerican accessions and Italian landraces belong to two distinct gene pools confirming the hypothesis that Europe could be considered a secondary diversification center for P. coccineus.

Antarctic glossopterid diversity on a local scale: the presence of multiple megasporophyll genera, Upper Permian, Mt. Achernar, Transantarctic Mountains, Antarctica.

PubMed

Ryberg, Patricia E; Taylor, Edith L; Taylor, Thomas N

2012-09-01

The glossopterids are a group of plants that thrived during a time of global warming similar to what is happening on the Earth today as well as the transition from archaic plant groups to the ancestors of modern groups. The diversity of the glossopterid clade is based on the megasporangiate structures assigned to the group, because the vegetative and pollen-bearing structures vary little. The presence of numerous reproductive genera from a single Upper Permian locality in the central Transantarctic Mountains provides important data on local glossopterid diversity in Antarctica. Impression/compression fossils were imaged with a Leica 5000C digital camera on a dissecting microscope or a Fujifilm FinePix S1pro digital camera. Two megasporangiate taxa are described: Scutum leiophyllum, which represents the first confirmed record of the genus in Antarctica, and Lidgettoniopsis ramulus, a new morphology consisting of a pinnate structure with oppositely attached megasporophylls. Plumsteadia ovata specimens indicate that this genus can be larger than previously recorded and illustrate the vegetative surface with a distinct midrib. The presence of a laminar, multiovulate structure and a pinnate structure at the same site indicates that local-level glossopterid diversity in Antarctica is greater than previously hypothesized. The discovery of a new megasporophyll morphology in Antarctica (confirming the presence of three distinctive morphologies on the continent) shows that Antarctic glossopterid heterogeneity is on a par with other Gondwanan continents. The diversity of the Antarctic landscape reveals that high polar latitudes can sustain a diverse ecosystem during times of global warming.

On structure-exploiting trust-region regularized nonlinear least squares algorithms for neural-network learning.

PubMed

Mizutani, Eiji; Demmel, James W

2003-01-01

This paper briefly introduces our numerical linear algebra approaches for solving structured nonlinear least squares problems arising from 'multiple-output' neural-network (NN) models. Our algorithms feature trust-region regularization, and exploit sparsity of either the 'block-angular' residual Jacobian matrix or the 'block-arrow' Gauss-Newton Hessian (or Fisher information matrix in statistical sense) depending on problem scale so as to render a large class of NN-learning algorithms 'efficient' in both memory and operation costs. Using a relatively large real-world nonlinear regression application, we shall explain algorithmic strengths and weaknesses, analyzing simulation results obtained by both direct and iterative trust-region algorithms with two distinct NN models: 'multilayer perceptrons' (MLP) and 'complementary mixtures of MLP-experts' (or neuro-fuzzy modular networks).

Enteroaggregative Escherichia coli have evolved independently as distinct complexes within the E. coli population with varying ability to cause disease.

PubMed

Chattaway, Marie Anne; Jenkins, Claire; Rajendram, Dunstan; Cravioto, Alejandro; Talukder, Kaisar Ali; Dallman, Tim; Underwood, Anthony; Platt, Steve; Okeke, Iruka N; Wain, John

2014-01-01

Enteroaggregative E. coli (EAEC) is an established diarrhoeagenic pathotype. The association with virulence gene content and ability to cause disease has been studied but little is known about the population structure of EAEC and how this pathotype evolved. Analysis by Multi Locus Sequence Typing of 564 EAEC isolates from cases and controls in Bangladesh, Nigeria and the UK spanning the past 29 years, revealed multiple successful lineages of EAEC. The population structure of EAEC indicates some clusters are statistically associated with disease or carriage, further highlighting the heterogeneous nature of this group of organisms. Different clusters have evolved independently as a result of both mutational and recombination events; the EAEC phenotype is distributed throughout the population of E. coli.

Machine-Learned Data Structures of Lipid Marker Serum Concentrations in Multiple Sclerosis Patients Differ from Those in Healthy Subjects

PubMed Central

Lötsch, Jörn; Thrun, Michael; Lerch, Florian; Brunkhorst, Robert; Schiffmann, Susanne; Thomas, Dominique; Tegder, Irmgard; Geisslinger, Gerd; Ultsch, Alfred

2017-01-01

Lipid signaling has been suggested to be a major pathophysiological mechanism of multiple sclerosis (MS). With the increasing knowledge about lipid signaling, acquired data become increasingly complex making bioinformatics necessary in lipid research. We used unsupervised machine-learning to analyze lipid marker serum concentrations, pursuing the hypothesis that for the most relevant markers the emerging data structures will coincide with the diagnosis of MS. Machine learning was implemented as emergent self-organizing feature maps (ESOM) combined with the U*-matrix visualization technique. The data space consisted of serum concentrations of three main classes of lipid markers comprising eicosanoids (d = 11 markers), ceramides (d = 10), and lyosophosphatidic acids (d = 6). They were analyzed in cohorts of MS patients (n = 102) and healthy subjects (n = 301). Clear data structures in the high-dimensional data space were observed in eicosanoid and ceramides serum concentrations whereas no clear structure could be found in lysophosphatidic acid concentrations. With ceramide concentrations, the structures that had emerged from unsupervised machine-learning almost completely overlapped with the known grouping of MS patients versus healthy subjects. This was only partly provided by eicosanoid serum concentrations. Thus, unsupervised machine-learning identified distinct data structures of bioactive lipid serum concentrations. These structures could be superimposed with the known grouping of MS patients versus healthy subjects, which was almost completely possible with ceramides. Therefore, based on the present analysis, ceramides are first-line candidates for further exploration as drug-gable targets or biomarkers in MS. PMID:28590455

Dynamic equilibrium of heterogeneous and interconvertible multipotent hematopoietic cell subsets

PubMed Central

Weston, Wendy; Zayas, Jennifer; Perez, Ruben; George, John; Jurecic, Roland

2014-01-01

Populations of hematopoietic stem cells and progenitors are quite heterogeneous and consist of multiple cell subsets with distinct phenotypic and functional characteristics. Some of these subsets also appear to be interconvertible and oscillate between functionally distinct states. The multipotent hematopoietic cell line EML has emerged as a unique model to study the heterogeneity and interconvertibility of multipotent hematopoietic cells. Here we describe extensive phenotypic and functional heterogeneity of EML cells which stems from the coexistence of multiple cell subsets. Each of these subsets is phenotypically and functionally heterogeneous, and displays distinct multilineage differentiation potential, cell cycle profile, proliferation kinetics, and expression pattern of HSC markers and some of the key lineage-associated transcription factors. Analysis of their maintenance revealed that on a population level all EML cell subsets exhibit cell-autonomous interconvertible properties, with the capacity to generate all other subsets and re-establish complete parental EML cell population. Moreover, all EML cell subsets generated during multiple cell generations maintain their distinct phenotypic and functional signatures and interconvertible properties. The model of EML cell line suggests that interconvertible multipotent hematopoietic cell subsets coexist in a homeostatically maintained dynamic equilibrium which is regulated by currently unknown cell-intrinsic mechanisms. PMID:24903657

Dynamic equilibrium of heterogeneous and interconvertible multipotent hematopoietic cell subsets.

PubMed

Weston, Wendy; Zayas, Jennifer; Perez, Ruben; George, John; Jurecic, Roland

2014-06-06

Populations of hematopoietic stem cells and progenitors are quite heterogeneous and consist of multiple cell subsets with distinct phenotypic and functional characteristics. Some of these subsets also appear to be interconvertible and oscillate between functionally distinct states. The multipotent hematopoietic cell line EML has emerged as a unique model to study the heterogeneity and interconvertibility of multipotent hematopoietic cells. Here we describe extensive phenotypic and functional heterogeneity of EML cells which stems from the coexistence of multiple cell subsets. Each of these subsets is phenotypically and functionally heterogeneous, and displays distinct multilineage differentiation potential, cell cycle profile, proliferation kinetics, and expression pattern of HSC markers and some of the key lineage-associated transcription factors. Analysis of their maintenance revealed that on a population level all EML cell subsets exhibit cell-autonomous interconvertible properties, with the capacity to generate all other subsets and re-establish complete parental EML cell population. Moreover, all EML cell subsets generated during multiple cell generations maintain their distinct phenotypic and functional signatures and interconvertible properties. The model of EML cell line suggests that interconvertible multipotent hematopoietic cell subsets coexist in a homeostatically maintained dynamic equilibrium which is regulated by currently unknown cell-intrinsic mechanisms.

Adaptation of flower and fruit colours to multiple, distinct mutualists.

PubMed

Renoult, Julien P; Valido, Alfredo; Jordano, Pedro; Schaefer, H Martin

2014-01-01

Communication in plant-animal mutualisms frequently involves multiple perceivers. A fundamental uncertainty is whether and how species adapt to communicate with groups of mutualists having distinct sensory abilities. We quantified the colour conspicuousness of flowers and fruits originating from one European and two South American plant communities, using visual models of pollinators (bee and fly) and seed dispersers (bird, primate and marten). We show that flowers are more conspicuous than fruits to pollinators, and the reverse to seed dispersers. In addition, flowers are more conspicuous to pollinators than to seed dispersers and the reverse for fruits. Thus, despite marked differences in the visual systems of mutualists, flower and fruit colours have evolved to attract multiple, distinct mutualists but not unintended perceivers. We show that this adaptation is facilitated by a limited correlation between flower and fruit colours, and by the fact that colour signals as coded at the photoreceptor level are more similar within than between functional groups (pollinators and seed dispersers). Overall, these results provide the first quantitative demonstration that flower and fruit colours are adaptations allowing plants to communicate simultaneously with distinct groups of mutualists. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

The separation between the 5'-3' ends in long RNA molecules is short and nearly constant.

PubMed

Leija-Martínez, Nehemías; Casas-Flores, Sergio; Cadena-Nava, Rubén D; Roca, Joan A; Mendez-Cabañas, José A; Gomez, Eduardo; Ruiz-Garcia, Jaime

2014-12-16

RNA molecules play different roles in coding, decoding and gene expression regulation. Such roles are often associated to the RNA secondary or tertiary structures. The folding dynamics lead to multiple secondary structures of long RNA molecules, since an RNA molecule might fold into multiple distinct native states. Despite an ensemble of different structures, it has been theoretically proposed that the separation between the 5' and 3' ends of long single-stranded RNA molecules (ssRNA) remains constant, independent of their base content and length. Here, we present the first experimental measurements of the end-to-end separation in long ssRNA molecules. To determine this separation, we use single molecule Fluorescence Resonance Energy Transfer of fluorescently end-labeled ssRNA molecules ranging from 500 to 5500 nucleotides in length, obtained from two viruses and a fungus. We found that the end-to-end separation is indeed short, within 5-9 nm. It is remarkable that the separation of the ends of all RNA molecules studied remains small and similar, despite the origin, length and differences in their secondary structure. This implies that the ssRNA molecules are 'effectively circularized' something that might be a general feature of RNAs, and could result in fine-tuning for translation and gene expression regulation. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Importance of Neutralizing Monoclonal Antibodies Targeting Multiple Antigenic Sites on the Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein To Avoid Neutralization Escape

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

Wang, Lingshu; Shi, Wei; Chappell, James D.

ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pulmonary infection with ~35% mortality. The potential for a future pandemic originating from animal reservoirs or health care-associated events is a major public health concern. There are no vaccines or therapeutic agents currently available for MERS-CoV. Using a probe-based single B cell cloning strategy, we have identified and characterized multiple neutralizing monoclonal antibodies (MAbs) specifically binding to the receptor-binding domain (RBD) or S1 (non-RBD) regions from a convalescent MERS-CoV-infected patient and from immunized rhesus macaques. RBD-specific MAbs tended to have greater neutralizing potency than non-RBD S1-specific MAbs. Six RBD-specificmore » and five S1-specific MAbs could be sorted into four RBD and three non-RBD distinct binding patterns, based on competition assays, mapping neutralization escape variants, and structural analysis. We determined cocrystal structures for two MAbs targeting the RBD from different angles and show they can bind the RBD only in the “out” position. We then showed that selected RBD-specific, non-RBD S1-specific, and S2-specific MAbs given prophylactically prevented MERS-CoV replication in lungs and protected mice from lethal challenge. Importantly, combining RBD- and non-RBD MAbs delayed the emergence of escape mutations in a cell-based virus escape assay. These studies identify MAbs targeting different antigenic sites on S that will be useful for defining mechanisms of MERS-CoV neutralization and for developing more effective interventions to prevent or treat MERS-CoV infections. IMPORTANCEMERS-CoV causes a highly lethal respiratory infection for which no vaccines or antiviral therapeutic options are currently available. Based on continuing exposure from established reservoirs in dromedary camels and bats, transmission of MERS-CoV into humans and future outbreaks are expected. Using structurally defined probes for the MERS-CoV spike glycoprotein (S), the target for neutralizing antibodies, single B cells were sorted from a convalescent human and immunized nonhuman primates (NHPs). MAbs produced from paired immunoglobulin gene sequences were mapped to multiple epitopes within and outside the receptor-binding domain (RBD) and protected against lethal MERS infection in a murine model following passive immunization. Importantly, combining MAbs targeting distinct epitopes prevented viral neutralization escape from RBD-directed MAbs. These data suggest that antibody responses to multiple domains on CoV spike protein may improve immunity and will guide future vaccine and therapeutic development efforts.« less

Adaptive Bloom Filter: A Space-Efficient Counting Algorithm for Unpredictable Network Traffic

NASA Astrophysics Data System (ADS)

Matsumoto, Yoshihide; Hazeyama, Hiroaki; Kadobayashi, Youki

The Bloom Filter (BF), a space-and-time-efficient hashcoding method, is used as one of the fundamental modules in several network processing algorithms and applications such as route lookups, cache hits, packet classification, per-flow state management or network monitoring. BF is a simple space-efficient randomized data structure used to represent a data set in order to support membership queries. However, BF generates false positives, and cannot count the number of distinct elements. A counting Bloom Filter (CBF) can count the number of distinct elements, but CBF needs more space than BF. We propose an alternative data structure of CBF, and we called this structure an Adaptive Bloom Filter (ABF). Although ABF uses the same-sized bit-vector used in BF, the number of hash functions employed by ABF is dynamically changed to record the number of appearances of a each key element. Considering the hash collisions, the multiplicity of a each key element on ABF can be estimated from the number of hash functions used to decode the membership of the each key element. Although ABF can realize the same functionality as CBF, ABF requires the same memory size as BF. We describe the construction of ABF and IABF (Improved ABF), and provide a mathematical analysis and simulation using Zipf's distribution. Finally, we show that ABF can be used for an unpredictable data set such as real network traffic.

Lightweight Thermoformed Structural Components and Optics

NASA Technical Reports Server (NTRS)

Zeiders, Glenn W.; Bradford, Larry J.

2004-01-01

A technique that involves the use of thermoformed plastics has been developed to enable the design and fabrication of ultra-lightweight structural components and mirrors for use in outer space. The technique could also be used to produce items for special terrestrial uses in which minimization of weight is a primary design consideration. Although the inherent strengths of thermoplastics are clearly inferior to those of metals and composite materials, thermoplastics offer a distinct advantage in that they can be shaped, at elevated temperatures, to replicate surfaces (e.g., prescribed mirror surfaces) precisely. Furthermore, multiple elements can be bonded into structures of homogeneous design that display minimal thermal deformation aside from simple expansion. The design aspect of the present technique is based on the principle that the deflection of a plate that has internal structure depends far more on the overall thickness than on the internal details; thus, a very stiff, light structure can be made from thin plastic that is heatformed to produce a sufficiently high moment of inertia. General examples of such structures include I beams and eggcrates.

Response of rocky invertebrate diversity, structure and function to the vertical layering of vegetation

NASA Astrophysics Data System (ADS)

Bustamante, María; Tajadura, Javier; Gorostiaga, José María; Saiz-Salinas, José Ignacio

2014-06-01

Macroalgae comprise a prominent part of the rocky benthos where many invertebrates develop, and are believed to be undergoing severe declines worldwide. In order to investigate how the vegetation structure (crustose, basal and canopy layers) contributes to the diversity, structure and function of benthic invertebrates, a total of 31 subtidal transects were sampled along the northeast Atlantic coast of Spain. Significant positive relationships were found between the canopy layer and faunal abundance, taxonomic diversity and functional group diversity. Canopy forming algae were also related to epiphytic invertebrates, medium size forms, colonial strategy and suspensivores. By contrast, basal algae showed negative relationships with all variables tested except for detritivores. Multivariate multiple regression analyses (DISTLM) point to crustose as well as canopy layers as the best link between seaweeds and invertebrate assemblage structure. A close relationship was found between taxonomic and functional diversities. In general, low levels of taxonomic redundancy were detected for functional groups correlated with vegetation structure. A conceptual model based on the results is proposed, describing distinct stages of invertebrate assemblages in relation to the vertical structure of vegetation.

Eukaryotic membrane tethers revisited using magnetic tweezers.

PubMed

Hosu, Basarab G; Sun, Mingzhai; Marga, Françoise; Grandbois, Michel; Forgacs, Gabor

2007-04-19

Membrane nanotubes, under physiological conditions, typically form en masse. We employed magnetic tweezers (MTW) to extract tethers from human brain tumor cells and compared their biophysical properties with tethers extracted after disruption of the cytoskeleton and from a strongly differing cell type, Chinese hamster ovary cells. In this method, the constant force produced with the MTW is transduced to cells through super-paramagnetic beads attached to the cell membrane. Multiple sudden jumps in bead velocity were manifest in the recorded bead displacement-time profiles. These discrete events were interpreted as successive ruptures of individual tethers. Observation with scanning electron microscopy supported the simultaneous existence of multiple tethers. The physical characteristics, in particular, the number and viscoelastic properties of the extracted tethers were determined from the analytic fit to bead trajectories, provided by a standard model of viscoelasticity. Comparison of tethers formed with MTW and atomic force microscopy (AFM), a technique where the cantilever-force transducer is moved at constant velocity, revealed significant differences in the two methods of tether formation. Our findings imply that extreme care must be used to interpret the outcome of tether pulling experiments performed with single molecular techniques (MTW, AFM, optical tweezers, etc). First, the different methods may be testing distinct membrane structures with distinct properties. Second, as soon as a true cell membrane (as opposed to that of a vesicle) can attach to a substrate, upon pulling on it, multiple nonspecific membrane tethers may be generated. Therefore, under physiological conditions, distinguishing between tethers formed through specific and nonspecific interactions is highly nontrivial if at all possible.

Eukaryotic membrane tethers revisited using magnetic tweezers

NASA Astrophysics Data System (ADS)

Hosu, Basarab G.; Sun, Mingzhai; Marga, Françoise; Grandbois, Michel; Forgacs, Gabor

2007-06-01

Membrane nanotubes, under physiological conditions, typically form en masse. We employed magnetic tweezers (MTW) to extract tethers from human brain tumor cells and compared their biophysical properties with tethers extracted after disruption of the cytoskeleton and from a strongly differing cell type, Chinese hamster ovary cells. In this method, the constant force produced with the MTW is transduced to cells through super-paramagnetic beads attached to the cell membrane. Multiple sudden jumps in bead velocity were manifest in the recorded bead displacement-time profiles. These discrete events were interpreted as successive ruptures of individual tethers. Observation with scanning electron microscopy supported the simultaneous existence of multiple tethers. The physical characteristics, in particular, the number and viscoelastic properties of the extracted tethers were determined from the analytic fit to bead trajectories, provided by a standard model of viscoelasticity. Comparison of tethers formed with MTW and atomic force microscopy (AFM), a technique where the cantilever-force transducer is moved at constant velocity, revealed significant differences in the two methods of tether formation. Our findings imply that extreme care must be used to interpret the outcome of tether pulling experiments performed with single molecular techniques (MTW, AFM, optical tweezers, etc). First, the different methods may be testing distinct membrane structures with distinct properties. Second, as soon as a true cell membrane (as opposed to that of a vesicle) can attach to a substrate, upon pulling on it, multiple nonspecific membrane tethers may be generated. Therefore, under physiological conditions, distinguishing between tethers formed through specific and nonspecific interactions is highly nontrivial if at all possible.

A highly-active and stable hydrogen evolution catalyst based on pyrite-structured cobalt phosphosulfide

DOE PAGES

Liu, Wen; Hu, Enyuan; Jiang, Hong; ...

2016-02-19

Rational design and controlled synthesis of hybrid structures comprising multiple components with distinctive functionalities are an intriguing and challenging approach to materials development for important energy applications like electrocatalytic hydrogen production, where there is a great need for cost effective, active and durable catalyst materials to replace the precious platinum. Here we report a structure design and sequential synthesis of a highly active and stable hydrogen evolution electrocatalyst material based on pyrite-structured cobalt phosphosulfide nanoparticles grown on carbon nanotubes. The three synthetic steps in turn render electrical conductivity, catalytic activity and stability to the material. The hybrid material exhibits superiormore » activity for hydrogen evolution, achieving current densities of 10 mA cm –2 and 100 mA cm –2 at overpotentials of 48 mV and 109 mV, respectively. Lastly, phosphorus substitution is crucial for the chemical stability and catalytic durability of the material, the molecular origins of which are uncovered by X-ray absorption spectroscopy and computational simulation.« less

Conformational Heterogeneity in a Fully Complementary DNA Three-Way Junction with a GC-Rich Branchpoint.

PubMed

Toulmin, Anita; Baltierra-Jasso, Laura E; Morten, Michael J; Sabir, Tara; McGlynn, Peter; Schröder, Gunnar F; Smith, Brian O; Magennis, Steven W

2017-09-19

DNA three-way junctions (3WJs) are branched structures that serve as important biological intermediates and as components in DNA nanostructures. We recently derived the global structure of a fully complementary 3WJ and found that it contained unpaired bases at the branchpoint, which is consistent with previous observations of branch flexibility and branchpoint reactivity. By combining high-resolution single-molecule Förster resonance energy transfer, molecular modeling, time-resolved ensemble fluorescence spectroscopy, and the first 19 F nuclear magnetic resonance observations of fully complementary 3WJs, we now show that the 3WJ structure can adopt multiple distinct conformations depending upon the sequence at the branchpoint. A 3WJ with a GC-rich branchpoint adopts an open conformation with unpaired bases at the branch and at least one additional conformation with an increased number of base interactions at the branchpoint. This structural diversity has implications for branch interactions and processing in vivo and for technological applications.

Optical and structural properties of cobalt-permalloy slanted columnar heterostructure thin films

NASA Astrophysics Data System (ADS)

Sekora, Derek; Briley, Chad; Schubert, Mathias; Schubert, Eva

2017-11-01

Optical and structural properties of sequential Co-column-NiFe-column slanted columnar heterostructure thin films with an Al2O3 passivation coating are reported. Electron-beam evaporated glancing angle deposition is utilized to deposit the sequential multiple-material slanted columnar heterostructure thin films. Mueller matrix generalized spectroscopic ellipsometry data is analyzed with a best-match model approach employing the anisotropic Bruggeman effective medium approximation formalism to determine bulk-like and anisotropic optical and structural properties of the individual Co and NiFe slanted columnar material sub-layers. Scanning electron microscopy is applied to image the Co-NiFe sequential growth properties and to verify the results of the ellipsometric analysis. Comparisons to single-material slanted columnar thin films and optically bulk solid thin films are presented and discussed. We find that the optical and structural properties of each material sub-layer of the sequential slanted columnar heterostructure film are distinct from each other and resemble those of their respective single-material counterparts.

Structural basis for Smoothened receptor modulation and chemoresistance to anti-cancer drugs

PubMed Central

Wang, Chong; Wu, Huixian; Evron, Tama; Vardy, Eyal; Han, Gye Won; Huang, Xi-Ping; Hufeisen, Sandy J.; Mangano, Thomas J.; Urban, Dan J.; Katritch, Vsevolod; Cherezov, Vadim; Caron, Marc G.; Roth, Bryan L.; Stevens, Raymond C.

2014-01-01

The Smoothened receptor (SMO) mediates signal transduction in the hedgehog pathway, which is implicated in normal development and carcinogenesis. SMO antagonists can suppress the growth of some tumors; however, mutations at SMO have been found to abolish their anti-tumor effects, a phenomenon known as chemoresistance. Here we report three crystal structures of human SMO bound to the antagonists SANT1 and Anta XV, and the agonist, SAG1.5, at 2.6–2.8Å resolution. The long and narrow cavity in the transmembrane domain of SMO harbors multiple ligand binding sites, where SANT1 binds at a deeper site as compared with other ligands. Distinct interactions at D4736.55 elucidated the structural basis for the differential effects of chemoresistance mutations on SMO antagonists. The agonist SAG1.5 induces a conformational rearrangement of the binding pocket residues, which could contribute to SMO activation. Collectively, these studies reveal the structural basis for the modulation of SMO by small molecules. PMID:25008467

Antimicrobial Peptides from Plants

PubMed Central

Tam, James P.; Wang, Shujing; Wong, Ka H.; Tan, Wei Liang

2015-01-01

Plant antimicrobial peptides (AMPs) have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs) of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic), lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms. PMID:26580629

Genome Structures and Transcriptomes Signify Niche Adaptation for the Multiple-Ion-Tolerant Extremophyte Schrenkiella parvula1[C][W][OPEN

PubMed Central

Oh, Dong-Ha; Hong, Hyewon; Lee, Sang Yeol; Yun, Dae-Jin; Bohnert, Hans J.; Dassanayake, Maheshi

2014-01-01

Schrenkiella parvula (formerly Thellungiella parvula), a close relative of Arabidopsis (Arabidopsis thaliana) and Brassica crop species, thrives on the shores of Lake Tuz, Turkey, where soils accumulate high concentrations of multiple-ion salts. Despite the stark differences in adaptations to extreme salt stresses, the genomes of S. parvula and Arabidopsis show extensive synteny. S. parvula completes its life cycle in the presence of Na+, K+, Mg2+, Li+, and borate at soil concentrations lethal to Arabidopsis. Genome structural variations, including tandem duplications and translocations of genes, interrupt the colinearity observed throughout the S. parvula and Arabidopsis genomes. Structural variations distinguish homologous gene pairs characterized by divergent promoter sequences and basal-level expression strengths. Comparative RNA sequencing reveals the enrichment of ion-transport functions among genes with higher expression in S. parvula, while pathogen defense-related genes show higher expression in Arabidopsis. Key stress-related ion transporter genes in S. parvula showed increased copy number, higher transcript dosage, and evidence for subfunctionalization. This extremophyte offers a framework to identify the requisite adjustments of genomic architecture and expression control for a set of genes found in most plants in a way to support distinct niche adaptation and lifestyles. PMID:24563282

Numerical Simulations of Silverpit Crater Collapse

NASA Technical Reports Server (NTRS)

Collins, G. S.; Turtle, E. P.; Melosh, H. J.

2003-01-01

The Silverpit crater is a recently discovered, 60-65 Myr old complex crater, which lies buried beneath the North Sea, about 150 km east of Britain. High-resolution images of Silverpit's subsurface structure, provided by three-dimensional seismic reflection data, reveal an inner-crater morphology similar to that expected for a 5-8 km diameter terrestrial crater. The crater walls show evidence of terracestyle slumping and there is a distinct central uplift, which may have produced a central peak in the pristine crater morphology. However, Silverpit is not a typical 5-km diameter terrestrial crater, because it exhibits multiple, concentric rings outside the main cavity. External concentric rings are normally associated with much larger impact structures, for example Chicxulub on Earth, or Orientale on the Moon. Furthermore, external rings associated with large impacts on the terrestrial planets and moons are widely-spaced, predominantly inwardly-facing, asymmetric scarps. However, the seismic data show that the external rings at Silverpit represent closely-spaced, concentric fault-bound graben, with both inwardly and outwardly facing faults-carps. This type of multi-ring structure is directly analogous to the Valhalla-type multi-ring basins found on the icy satellites. Thus, the presence and style of the multiple rings at Silverpit is surprising given both the size of the crater and its planetary setting.

Structural determinants of APOBEC3B non-catalytic domain for molecular assembly and catalytic regulation

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

Xiao, Xiao; Yang, Hanjing; Arutiunian, Vagan

The catalytic activity of human cytidine deaminase APOBEC3B (A3B) has been correlated with kataegic mutational patterns within multiple cancer types. The molecular basis of how the N-terminal non-catalytic CD1 regulates the catalytic activity and consequently, biological function of A3B remains relatively unknown. Here, we report the crystal structure of a soluble human A3B-CD1 variant and delineate several structural elements of CD1 involved in molecular assembly, nucleic acid interactions and catalytic regulation of A3B. We show that (i) A3B expressed in human cells exists in hypoactive high-molecular-weight (HMW) complexes, which can be activated without apparent dissociation into low-molecular-weight (LMW) species aftermore » RNase A treatment. (ii) Multiple surface hydrophobic residues of CD1 mediate the HMW complex assembly and affect the catalytic activity, including one tryptophan residue W127 that likely acts through regulating nucleic acid binding. (iii) One of the highly positively charged surfaces on CD1 is involved in RNA-dependent attenuation of A3B catalysis. (iv) Surface hydrophobic residues of CD1 are involved in heterogeneous nuclear ribonucleoproteins (hnRNPs) binding to A3B. The structural and biochemical insights described here suggest that unique structural features on CD1 regulate the molecular assembly and catalytic activity of A3B through distinct mechanisms.« less

4D multiple-cathode ultrafast electron microscopy

PubMed Central

Baskin, John Spencer; Liu, Haihua; Zewail, Ahmed H.

2014-01-01

Four-dimensional multiple-cathode ultrafast electron microscopy is developed to enable the capture of multiple images at ultrashort time intervals for a single microscopic dynamic process. The dynamic process is initiated in the specimen by one femtosecond light pulse and probed by multiple packets of electrons generated by one UV laser pulse impinging on multiple, spatially distinct, cathode surfaces. Each packet is distinctly recorded, with timing and detector location controlled by the cathode configuration. In the first demonstration, two packets of electrons on each image frame (of the CCD) probe different times, separated by 19 picoseconds, in the evolution of the diffraction of a gold film following femtosecond heating. Future elaborations of this concept to extend its capabilities and expand the range of applications of 4D ultrafast electron microscopy are discussed. The proof-of-principle demonstration reported here provides a path toward the imaging of irreversible ultrafast phenomena of materials, and opens the door to studies involving the single-frame capture of ultrafast dynamics using single-pump/multiple-probe, embedded stroboscopic imaging. PMID:25006261

4D multiple-cathode ultrafast electron microscopy.

PubMed

Baskin, John Spencer; Liu, Haihua; Zewail, Ahmed H

2014-07-22

Four-dimensional multiple-cathode ultrafast electron microscopy is developed to enable the capture of multiple images at ultrashort time intervals for a single microscopic dynamic process. The dynamic process is initiated in the specimen by one femtosecond light pulse and probed by multiple packets of electrons generated by one UV laser pulse impinging on multiple, spatially distinct, cathode surfaces. Each packet is distinctly recorded, with timing and detector location controlled by the cathode configuration. In the first demonstration, two packets of electrons on each image frame (of the CCD) probe different times, separated by 19 picoseconds, in the evolution of the diffraction of a gold film following femtosecond heating. Future elaborations of this concept to extend its capabilities and expand the range of applications of 4D ultrafast electron microscopy are discussed. The proof-of-principle demonstration reported here provides a path toward the imaging of irreversible ultrafast phenomena of materials, and opens the door to studies involving the single-frame capture of ultrafast dynamics using single-pump/multiple-probe, embedded stroboscopic imaging.

The taccalonolides and paclitaxel cause distinct effects on microtubule dynamics and aster formation

PubMed Central

2014-01-01

Background Microtubule stabilizers suppress microtubule dynamics and, at the lowest antiproliferative concentrations, disrupt the function of mitotic spindles, leading to mitotic arrest and apoptosis. At slightly higher concentrations, these agents cause the formation of multiple mitotic asters with distinct morphologies elicited by different microtubule stabilizers. Results We tested the hypothesis that two classes of microtubule stabilizing drugs, the taxanes and the taccalonolides, cause the formation of distinct aster structures due, in part, to differential effects on microtubule dynamics. Paclitaxel and the taccalonolides suppressed the dynamics of microtubules formed from purified tubulin as well as in live cells. Both agents suppressed microtubule dynamic instability, with the taccalonolides having a more pronounced inhibition of microtubule catastrophe, suggesting that they stabilize the plus ends of microtubules more effectively than paclitaxel. Live cell microscopy was also used to evaluate the formation and resolution of asters after drug treatment. While each drug had similar effects on initial formation, substantial differences were observed in aster resolution. Paclitaxel-induced asters often coalesced over time resulting in fewer, larger asters whereas numerous compact asters persisted once they were formed in the presence of the taccalonolides. Conclusions We conclude that the increased resistance of microtubule plus ends to catastrophe may play a role in the observed inability of taccalonolide-induced asters to coalesce during mitosis, giving rise to the distinct morphologies observed after exposure to these agents. PMID:24576146

Bayesian phylogeny of sucrose transporters: ancient origins, differential expansion and convergent evolution in monocots and dicots

PubMed Central

Peng, Duo; Gu, Xi; Xue, Liang-Jiao; Leebens-Mack, James H.; Tsai, Chung-Jui

2014-01-01

Sucrose transporters (SUTs) are essential for the export and efficient movement of sucrose from source leaves to sink organs in plants. The angiosperm SUT family was previously classified into three or four distinct groups, Types I, II (subgroup IIB), and III, with dicot-specific Type I and monocot-specific Type IIB functioning in phloem loading. To shed light on the underlying drivers of SUT evolution, Bayesian phylogenetic inference was undertaken using 41 sequenced plant genomes, including seven basal lineages at key evolutionary junctures. Our analysis supports four phylogenetically and structurally distinct SUT subfamilies, originating from two ancient groups (AG1 and AG2) that diverged early during terrestrial colonization. In both AG1 and AG2, multiple intron acquisition events in the progenitor vascular plant established the gene structures of modern SUTs. Tonoplastic Type III and plasmalemmal Type II represent evolutionarily conserved descendants of AG1 and AG2, respectively. Type I and Type IIB were previously thought to evolve after the dicot-monocot split. We show, however, that divergence of Type I from Type III SUT predated basal angiosperms, likely associated with evolution of vascular cambium and phloem transport. Type I SUT was subsequently lost in monocots along with vascular cambium, and independent evolution of Type IIB coincided with modified monocot vasculature. Both Type I and Type IIB underwent lineage-specific expansion. In multiple unrelated taxa, the newly-derived SUTs exhibit biased expression in reproductive tissues, suggesting a functional link between phloem loading and reproductive fitness. Convergent evolution of Type I and Type IIB for SUT function in phloem loading and reproductive organs supports the idea that differential vascular development in dicots and monocots is a strong driver for SUT family evolution in angiosperms. PMID:25429293

Multiple Emplacement and Exhumation History of the Late Mesozoic Dayunshan-Mufushan Batholith in Southeast China and Its Tectonic Significance: 2. Magnetic Fabrics and Gravity Survey

NASA Astrophysics Data System (ADS)

Ji, Wenbin; Chen, Yan; Chen, Ke; Wei, Wei; Faure, Michel; Lin, Wei

2018-01-01

The Late Mesozoic magmatic province is a prominent feature of the South China Block (SCB). However, the tectonic regimes associated with the magmatism are still elusive. A combined anisotropy of magnetic susceptibility and gravity study has been carried out to determine the fabric patterns and shape at depth of the Dayunshan-Mufushan composite batholith in the north-central SCB. This is a companion paper to Part 1 that presented the structural and geochronological data of this batholith. The magnetic fabrics in the batholith interior predominantly reflect magma flow structures. Two distinct patterns of the magnetic lineations are defined, around NNE-SSW and WNW-ESE trends for the early-stage and late-stage intrusions of the batholith, respectively. The gravity survey reveals that the early-stage intrusion has a main feeder zone located below its northern part, while several linear feeder zones trending NNE-SSW are inferred for the late-stage intrusion. Integrating all results, a two-stage construction of the batholith with distinct tectonic regimes has been established. It is concluded that the early-stage intrusion experienced a southward magma transport during its emplacement, partially assisted by far-field compression from the north at ca. 150 Ma. Conversely, the emplacement and exhumation of the late-stage intrusion was accommodated by a NW-SE crustal stretching involving a lateral magma expansion above the multiple feeder zones (likely corresponding to extensional fractures) and ductile shearing during 132-95 Ma localized mainly along the Dayunshan detachment fault. Finally, we discuss the geodynamic linkage between the paleo-Pacific subduction and the Late Mesozoic tectonomagmatism in the SCB.

Hue distinctiveness overrides category in determining performance in multiple object tracking.

PubMed

Sun, Mengdan; Zhang, Xuemin; Fan, Lingxia; Hu, Luming

2018-02-01

The visual distinctiveness between targets and distractors can significantly facilitate performance in multiple object tracking (MOT), in which color is a feature that has been commonly used. However, the processing of color can be more than "visual." Color is continuous in chromaticity, while it is commonly grouped into discrete categories (e.g., red, green). Evidence from color perception suggested that color categories may have a unique role in visual tasks independent of its chromatic appearance. Previous MOT studies have not examined the effect of chromatic and categorical distinctiveness on tracking separately. The current study aimed to reveal how chromatic (hue) and categorical distinctiveness of color between the targets and distractors affects tracking performance. With four experiments, we showed that tracking performance was largely facilitated by the increasing hue distance between the target set and the distractor set, suggesting that perceptual grouping was formed based on hue distinctiveness to aid tracking. However, we found no color categorical effect, because tracking performance was not significantly different when the targets and distractors were from the same or different categories. It was concluded that the chromatic distinctiveness of color overrides category in determining tracking performance, suggesting a dominant role of perceptual feature in MOT.

Interventional effects for mediation analysis with multiple mediators

PubMed Central

Vansteelandt, Stijn; Daniel, Rhian M.

2016-01-01

The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator–outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that involve repeatedly measured mediators, or multiple correlated mediators. VanderWeele, Vansteelandt, and Robins21 introduced so-called interventional (in)direct effects. These can be identified under much weaker conditions than natural (in)direct effects, but have the drawback of not adding up to the total effect. In this article, we adapt their proposal in order to achieve an exact decomposition of the total effect, and extend it to the multiple mediator setting. Interestingly, the proposed effects capture the path-specific effects of an exposure on an outcome that are mediated by distinct mediators, even when – as often – the structural dependence between the multiple mediators is unknown; for instance, when the direction of the causal effects between the mediators is unknown, or there may be unmeasured common causes of the mediators. PMID:27922534

Interventional Effects for Mediation Analysis with Multiple Mediators.

PubMed

Vansteelandt, Stijn; Daniel, Rhian M

2017-03-01

The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator-outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that involve repeatedly measured mediators, or multiple correlated mediators. VanderWeele, Vansteelandt, and Robins introduced so-called interventional (in)direct effects. These can be identified under much weaker conditions than natural (in)direct effects, but have the drawback of not adding up to the total effect. In this article, we adapt their proposal to achieve an exact decomposition of the total effect, and extend it to the multiple mediator setting. Interestingly, the proposed effects capture the path-specific effects of an exposure on an outcome that are mediated by distinct mediators, even when-as often-the structural dependence between the multiple mediators is unknown, for instance, when the direction of the causal effects between the mediators is unknown, or there may be unmeasured common causes of the mediators.

Similar bowtie structures and distinct largest strong components are identified in the transcriptional regulatory networks of Arabidopsis thaliana during photomorphogenesis and heat shock.

PubMed

Luo, Shitao; Zhang, Fengming; Ruan, Yingfei; Li, Jie; Zhang, Zheng; Sun, Yan; Deng, Shixiong; Peng, Rui

2018-06-01

Photomorphogenesis and heat shock are critical biological processes of plants. A recent research constructed the transcriptional regulatory networks (TRNs) of Arabidopsis thaliana during these processes using DNase-seq. In this study, by strong decomposition, we revealed that each of these TRNs can be represented as a similar bowtie structure with only one non-trivial and distinct strong component. We further identified distinct patterns of variation of a few light-related genes in these bowtie structures during photomorphogenesis. These results suggest that bowtie structure may be a common property of TRNs of plants, and distinct variation patterns of genes in bowtie structures of TRNs during biological processes may reflect distinct functions. Overall, our study provides an insight into the molecular mechanisms underlying photomorphogenesis and heat shock, and emphasizes the necessity to investigate the strong connectivity structures while studying TRNs. Copyright © 2018 Elsevier B.V. All rights reserved.

Spontaneous Epithelioid Hemangiosarcoma in a Rhesus Monkey (Macaca mulatta)

PubMed Central

Tsuchiya, Takayuki; Gray, Tasha L; Gatto, Nicholas T; Forest, Thomas; Machotka, Sam V; Troth, Sean P; Prahalada, Srinivasa

2014-01-01

Epithelioid hemangiosarcoma is a rare malignant endothelial neoplasia with a unique, predominantly epithelioid morphology. A 4-y-old rhesus monkey from our laboratory had multiple neoplastic nodules in a digit, limb skin, hindlimb muscle, and visceral organs including lung, heart, and brain. The nodules were composed of pleomorphic, polygonal, epithelioid, neoplastic cells that were arranged in sheets, nests, and cords and supported by variably dense fibrovascular connective tissue. The morphologic features of this tumor were predominantly epithelioid. However, some regions contained cystic spaces, clefts, and channel-like structures, all of which were lined with morphologically distinct neoplastic endothelial cells. These neoplastic cells, with or without epithelioid morphology, were positive immunohistochemically for CD31, factor VIII-related antigen, and vimentin. The presence of multiple metastatic nodules, high mitotic rate, and extensive Ki67-positive staining were consistent with malignancy. This report is the first description of epithelioid hemangiosarcoma in a rhesus monkey. PMID:25296017

Spontaneous epithelioid hemangiosarcoma in a rhesus monkey (Macaca mulatta).

PubMed

Tsuchiya, Takayuki; Gray, Tasha L; Gatto, Nicholas T; Forest, Thomas; Machotka, Sam V; Troth, Sean P; Prahalada, Srinivasa

2014-08-01

Epithelioid hemangiosarcoma is a rare malignant endothelial neoplasia with a unique, predominantly epithelioid morphology. A 4-y-old rhesus monkey from our laboratory had multiple neoplastic nodules in a digit, limb skin, hindlimb muscle, and visceral organs including lung, heart, and brain. The nodules were composed of pleomorphic, polygonal, epithelioid, neoplastic cells that were arranged in sheets, nests, and cords and supported by variably dense fibrovascular connective tissue. The morphologic features of this tumor were predominantly epithelioid. However, some regions contained cystic spaces, clefts, and channel-like structures, all of which were lined with morphologically distinct neoplastic endothelial cells. These neoplastic cells, with or without epithelioid morphology, were positive immunohistochemically for CD31, factor VIII-related antigen, and vimentin. The presence of multiple metastatic nodules, high mitotic rate, and extensive Ki67-positive staining were consistent with malignancy. This report is the first description of epithelioid hemangiosarcoma in a rhesus monkey.

Muscle networks: Connectivity analysis of EMG activity during postural control

NASA Astrophysics Data System (ADS)

Boonstra, Tjeerd W.; Danna-Dos-Santos, Alessander; Xie, Hong-Bo; Roerdink, Melvyn; Stins, John F.; Breakspear, Michael

2015-12-01

Understanding the mechanisms that reduce the many degrees of freedom in the musculoskeletal system remains an outstanding challenge. Muscle synergies reduce the dimensionality and hence simplify the control problem. How this is achieved is not yet known. Here we use network theory to assess the coordination between multiple muscles and to elucidate the neural implementation of muscle synergies. We performed connectivity analysis of surface EMG from ten leg muscles to extract the muscle networks while human participants were standing upright in four different conditions. We observed widespread connectivity between muscles at multiple distinct frequency bands. The network topology differed significantly between frequencies and between conditions. These findings demonstrate how muscle networks can be used to investigate the neural circuitry of motor coordination. The presence of disparate muscle networks across frequencies suggests that the neuromuscular system is organized into a multiplex network allowing for parallel and hierarchical control structures.

Dissociation in virtual reality: depersonalization and derealization

NASA Astrophysics Data System (ADS)

Garvey, Gregory P.

2010-01-01

This paper looks at virtual worlds such as Second Life7 (SL) as possible incubators of dissociation disorders as classified by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition3 (also known as the DSM-IV). Depersonalization is where "a person feels that he or she has changed in some way or is somehow unreal." Derealization when "the same beliefs are held about one's surroundings." Dissociative Identity Disorder (DID), previously known as multiple personality disorder fits users of Second Life who adopt "in-world" avatars and in effect, enact multiple distinct identities or personalities (known as alter egos or alters). Select questions from the Structured Clinical Interview for Depersonalization (SCI-DER)8 will be discussed as they might apply to the user's experience in Second Life. Finally I would like to consider the hypothesis that rather than a pathological disorder, dissociation is a normal response to the "artificial reality" of Second Life.

Cooperativity in Monomeric Enzymes with Single Ligand-Binding Sites

PubMed Central

Porter, Carol M.

2011-01-01

Cooperativity is widespread in biology. It empowers a variety of regulatory mechanisms and impacts both the kinetic and thermodynamic properties of macromolecular systems. Traditionally, cooperativity is viewed as requiring the participation of multiple, spatially distinct binding sites that communicate via ligand-induced structural rearrangements; however, cooperativity requires neither multiple ligand binding events nor multimeric assemblies. An underappreciated manifestation of cooperativity has been observed in the non-Michaelis-Menten kinetic response of certain monomeric enzymes that possess only a single ligand-binding site. In this review, we present an overview of kinetic cooperativity in monomeric enzymes. We discuss the primary mechanisms postulated to give rise to monomeric cooperativity and highlight modern experimental methods that could offer new insights into the nature of this phenomenon. We conclude with an updated list of single subunit enzymes that are suspected of displaying cooperativity, and a discussion of the biological significance of this unique kinetic response. PMID:22137502

Integrated photoacoustic, ultrasound and fluorescence platform for diagnostic medical imaging-proof of concept study with a tissue mimicking phantom.

PubMed

James, Joseph; Murukeshan, Vadakke Matham; Woh, Lye Sun

2014-07-01

The structural and molecular heterogeneities of biological tissues demand the interrogation of the samples with multiple energy sources and provide visualization capabilities at varying spatial resolution and depth scales for obtaining complementary diagnostic information. A novel multi-modal imaging approach that uses optical and acoustic energies to perform photoacoustic, ultrasound and fluorescence imaging at multiple resolution scales from the tissue surface and depth is proposed in this paper. The system comprises of two distinct forms of hardware level integration so as to have an integrated imaging system under a single instrumentation set-up. The experimental studies show that the system is capable of mapping high resolution fluorescence signatures from the surface, optical absorption and acoustic heterogeneities along the depth (>2cm) of the tissue at multi-scale resolution (<1µm to <0.5mm).

Multiple sclerosis lesions affect intrinsic functional connectivity of the spinal cord.

PubMed

Conrad, Benjamin N; Barry, Robert L; Rogers, Baxter P; Maki, Satoshi; Mishra, Arabinda; Thukral, Saakshi; Sriram, Subramaniam; Bhatia, Aashim; Pawate, Siddharama; Gore, John C; Smith, Seth A

2018-06-01

Patients with multiple sclerosis present with focal lesions throughout the spinal cord. There is a clinical need for non-invasive measurements of spinal cord activity and functional organization in multiple sclerosis, given the cord's critical role in the disease. Recent reports of spontaneous blood oxygenation level-dependent fluctuations in the spinal cord using functional MRI suggest that, like the brain, cord activity at rest is organized into distinct, synchronized functional networks among grey matter regions, likely related to motor and sensory systems. Previous studies looking at stimulus-evoked activity in the spinal cord of patients with multiple sclerosis have demonstrated increased levels of activation as well as a more bilateral distribution of activity compared to controls. Functional connectivity studies of brain networks in multiple sclerosis have revealed widespread alterations, which may take on a dynamic trajectory over the course of the disease, with compensatory increases in connectivity followed by decreases associated with structural damage. We build upon this literature by examining functional connectivity in the spinal cord of patients with multiple sclerosis. Using ultra-high field 7 T imaging along with processing strategies for robust spinal cord functional MRI and lesion identification, the present study assessed functional connectivity within cervical cord grey matter of patients with relapsing-remitting multiple sclerosis (n = 22) compared to a large sample of healthy controls (n = 56). Patient anatomical images were rated for lesions by three independent raters, with consensus ratings revealing 19 of 22 patients presented with lesions somewhere in the imaged volume. Linear mixed models were used to assess effects of lesion location on functional connectivity. Analysis in control subjects demonstrated a robust pattern of connectivity among ventral grey matter regions as well as a distinct network among dorsal regions. A gender effect was also observed in controls whereby females demonstrated higher ventral network connectivity. Wilcoxon rank-sum tests detected no differences in average connectivity or power of low frequency fluctuations in patients compared to controls. The presence of lesions was, however, associated with local alterations in connectivity with differential effects depending on columnar location. The patient results suggest that spinal cord functional networks are generally intact in relapsing-remitting multiple sclerosis but that lesions are associated with focal abnormalities in intrinsic connectivity. These findings are discussed in light of the current literature on spinal cord functional MRI and the potential neurological underpinnings.

Multiple Cognitive Control Effects of Error Likelihood and Conflict

PubMed Central

Brown, Joshua W.

2010-01-01

Recent work on cognitive control has suggested a variety of performance monitoring functions of the anterior cingulate cortex, such as errors, conflict, error likelihood, and others. Given the variety of monitoring effects, a corresponding variety of control effects on behavior might be expected. This paper explores whether conflict and error likelihood produce distinct cognitive control effects on behavior, as measured by response time. A change signal task (Brown & Braver, 2005) was modified to include conditions of likely errors due to tardy as well as premature responses, in conditions with and without conflict. The results discriminate between competing hypotheses of independent vs. interacting conflict and error likelihood control effects. Specifically, the results suggest that the likelihood of premature vs. tardy response errors can lead to multiple distinct control effects, which are independent of cognitive control effects driven by response conflict. As a whole, the results point to the existence of multiple distinct cognitive control mechanisms and challenge existing models of cognitive control that incorporate only a single control signal. PMID:19030873

Visualisation of variable binding pockets on protein surfaces by probabilistic analysis of related structure sets.

PubMed

Ashford, Paul; Moss, David S; Alex, Alexander; Yeap, Siew K; Povia, Alice; Nobeli, Irene; Williams, Mark A

2012-03-14

Protein structures provide a valuable resource for rational drug design. For a protein with no known ligand, computational tools can predict surface pockets that are of suitable size and shape to accommodate a complementary small-molecule drug. However, pocket prediction against single static structures may miss features of pockets that arise from proteins' dynamic behaviour. In particular, ligand-binding conformations can be observed as transiently populated states of the apo protein, so it is possible to gain insight into ligand-bound forms by considering conformational variation in apo proteins. This variation can be explored by considering sets of related structures: computationally generated conformers, solution NMR ensembles, multiple crystal structures, homologues or homology models. It is non-trivial to compare pockets, either from different programs or across sets of structures. For a single structure, difficulties arise in defining particular pocket's boundaries. For a set of conformationally distinct structures the challenge is how to make reasonable comparisons between them given that a perfect structural alignment is not possible. We have developed a computational method, Provar, that provides a consistent representation of predicted binding pockets across sets of related protein structures. The outputs are probabilities that each atom or residue of the protein borders a predicted pocket. These probabilities can be readily visualised on a protein using existing molecular graphics software. We show how Provar simplifies comparison of the outputs of different pocket prediction algorithms, of pockets across multiple simulated conformations and between homologous structures. We demonstrate the benefits of use of multiple structures for protein-ligand and protein-protein interface analysis on a set of complexes and consider three case studies in detail: i) analysis of a kinase superfamily highlights the conserved occurrence of surface pockets at the active and regulatory sites; ii) a simulated ensemble of unliganded Bcl2 structures reveals extensions of a known ligand-binding pocket not apparent in the apo crystal structure; iii) visualisations of interleukin-2 and its homologues highlight conserved pockets at the known receptor interfaces and regions whose conformation is known to change on inhibitor binding. Through post-processing of the output of a variety of pocket prediction software, Provar provides a flexible approach to the analysis and visualization of the persistence or variability of pockets in sets of related protein structures.

Combining Graphical and Analytical Methods with Molecular Simulations To Analyze Time-Resolved FRET Measurements of Labeled Macromolecules Accurately

PubMed Central

2017-01-01

Förster resonance energy transfer (FRET) measurements from a donor, D, to an acceptor, A, fluorophore are frequently used in vitro and in live cells to reveal information on the structure and dynamics of DA labeled macromolecules. Accurate descriptions of FRET measurements by molecular models are complicated because the fluorophores are usually coupled to the macromolecule via flexible long linkers allowing for diffusional exchange between multiple states with different fluorescence properties caused by distinct environmental quenching, dye mobilities, and variable DA distances. It is often assumed for the analysis of fluorescence intensity decays that DA distances and D quenching are uncorrelated (homogeneous quenching by FRET) and that the exchange between distinct fluorophore states is slow (quasistatic). This allows us to introduce the FRET-induced donor decay, εD(t), a function solely depending on the species fraction distribution of the rate constants of energy transfer by FRET, for a convenient joint analysis of fluorescence decays of FRET and reference samples by integrated graphical and analytical procedures. Additionally, we developed a simulation toolkit to model dye diffusion, fluorescence quenching by the protein surface, and FRET. A benchmark study with simulated fluorescence decays of 500 protein structures demonstrates that the quasistatic homogeneous model works very well and recovers for single conformations the average DA distances with an accuracy of < 2%. For more complex cases, where proteins adopt multiple conformations with significantly different dye environments (heterogeneous case), we introduce a general analysis framework and evaluate its power in resolving heterogeneities in DA distances. The developed fast simulation methods, relying on Brownian dynamics of a coarse-grained dye in its sterically accessible volume, allow us to incorporate structural information in the decay analysis for heterogeneous cases by relating dye states with protein conformations to pave the way for fluorescence and FRET-based dynamic structural biology. Finally, we present theories and simulations to assess the accuracy and precision of steady-state and time-resolved FRET measurements in resolving DA distances on the single-molecule and ensemble level and provide a rigorous framework for estimating approximation, systematic, and statistical errors. PMID:28709377

Issues and Perspectives in Species Delimitation using Phenotypic Data: Atlantean Evolution in Darwin's Finches.

PubMed

Cadena, Carlos Daniel; Zapata, Felipe; Jiménez, Iván

2018-03-01

Progress in the development and use of methods for species delimitation employing phenotypic data lags behind conceptual and practical advances in molecular genetic approaches. The basic evolutionary model underlying the use of phenotypic data to delimit species assumes random mating and quantitative polygenic traits, so that phenotypic distributions within a species should be approximately normal for individuals of the same sex and age. Accordingly, two or more distinct normal distributions of phenotypic traits suggest the existence of multiple species. In light of this model, we show that analytical approaches employed in taxonomic studies using phenotypic data are often compromised by three issues: 1) reliance on graphical analyses that convey little information on phenotype frequencies; 2) exclusion of characters potentially important for species delimitation following reduction of data dimensionality; and 3) use of measures of central tendency to evaluate phenotypic distinctiveness. We outline approaches to overcome these issues based on statistical developments related to normal mixture models (NMMs) and illustrate them empirically with a reanalysis of morphological data recently used to claim that there are no morphologically distinct species of Darwin's ground-finches (Geospiza). We found negligible support for this claim relative to taxonomic hypotheses recognizing multiple species. Although species limits among ground-finches merit further assessments using additional sources of information, our results bear implications for other areas of inquiry including speciation research: because ground-finches have likely speciated and are not trapped in a process of "Sisyphean" evolution as recently argued, they remain useful models to understand the evolutionary forces involved in speciation. Our work underscores the importance of statistical approaches grounded on appropriate evolutionary models for species delimitation. We discuss how NMMs offer new perspectives in the kind of inferences available to systematists, with significant repercussions on ideas about the phenotypic structure of biodiversity.

Cognitive control over learning: Creating, clustering and generalizing task-set structure

PubMed Central

Collins, Anne G.E.; Frank, Michael J.

2013-01-01

Executive functions and learning share common neural substrates essential for their expression, notably in prefrontal cortex and basal ganglia. Understanding how they interact requires studying how cognitive control facilitates learning, but also how learning provides the (potentially hidden) structure, such as abstract rules or task-sets, needed for cognitive control. We investigate this question from three complementary angles. First, we develop a new computational “C-TS” (context-task-set) model inspired by non-parametric Bayesian methods, specifying how the learner might infer hidden structure and decide whether to re-use that structure in new situations, or to create new structure. Second, we develop a neurobiologically explicit model to assess potential mechanisms of such interactive structured learning in multiple circuits linking frontal cortex and basal ganglia. We systematically explore the link betweens these levels of modeling across multiple task demands. We find that the network provides an approximate implementation of high level C-TS computations, where manipulations of specific neural mechanisms are well captured by variations in distinct C-TS parameters. Third, this synergism across models yields strong predictions about the nature of human optimal and suboptimal choices and response times during learning. In particular, the models suggest that participants spontaneously build task-set structure into a learning problem when not cued to do so, which predicts positive and negative transfer in subsequent generalization tests. We provide evidence for these predictions in two experiments and show that the C-TS model provides a good quantitative fit to human sequences of choices in this task. These findings implicate a strong tendency to interactively engage cognitive control and learning, resulting in structured abstract representations that afford generalization opportunities, and thus potentially long-term rather than short-term optimality. PMID:23356780

In-Depth View of the Structure and Growth of SnO2 Nanowires and Nanobrushes.

PubMed

Stuckert, Erin P; Geiss, Roy H; Miller, Christopher J; Fisher, Ellen R

2016-08-31

Strategic application of an array of complementary imaging and diffraction techniques is critical to determine accurate structural information on nanomaterials, especially when also seeking to elucidate structure-property relationships and their effects on gas sensors. In this work, SnO2 nanowires and nanobrushes grown via chemical vapor deposition (CVD) displayed the same tetragonal SnO2 structure as revealed via powder X-ray diffraction bulk crystallinity data. Additional characterization using a range of electron microscopy imaging and diffraction techniques, however, revealed important structure and morphology distinctions between the nanomaterials. Tailoring scanning transmission electron microscopy (STEM) modes combined with transmission electron backscatter diffraction (t-EBSD) techniques afforded a more detailed view of the SnO2 nanostructures. Indeed, upon deeper analysis of individual wires and brushes, we discovered that, despite a similar bulk structure, wires and brushes grew with different crystal faces and lattice spacings. Had we not utilized multiple STEM diffraction modes in conjunction with t-EBSD, differences in orientation related to bristle density would have been overlooked. Thus, it is only through a methodical combination of several structural analysis techniques that precise structural information can be reliably obtained.

Synergy and contingency as driving forces for the evolution of multiple secondary metabolite production by Streptomyces species.

PubMed

Challis, Gregory L; Hopwood, David A

2003-11-25

In this article we briefly review theories about the ecological roles of microbial secondary metabolites and discuss the prevalence of multiple secondary metabolite production by strains of Streptomyces, highlighting results from analysis of the recently sequenced Streptomyces coelicolor and Streptomyces avermitilis genomes. We address this question: Why is multiple secondary metabolite production in Streptomyces species so commonplace? We argue that synergy or contingency in the action of individual metabolites against biological competitors may, in some cases, be a powerful driving force for the evolution of multiple secondary metabolite production. This argument is illustrated with examples of the coproduction of synergistically acting antibiotics and contingently acting siderophores: two well-known classes of secondary metabolite. We focus, in particular, on the coproduction of beta-lactam antibiotics and beta-lactamase inhibitors, the coproduction of type A and type B streptogramins, and the coregulated production and independent uptake of structurally distinct siderophores by species of Streptomyces. Possible mechanisms for the evolution of multiple synergistic and contingent metabolite production in Streptomyces species are discussed. It is concluded that the production by Streptomyces species of two or more secondary metabolites that act synergistically or contingently against biological competitors may be far more common than has previously been recognized, and that synergy and contingency may be common driving forces for the evolution of multiple secondary metabolite production by these sessile saprophytes.

Synergy and contingency as driving forces for the evolution of multiple secondary metabolite production by Streptomyces species

PubMed Central

Challis, Gregory L.; Hopwood, David A.

2003-01-01

In this article we briefly review theories about the ecological roles of microbial secondary metabolites and discuss the prevalence of multiple secondary metabolite production by strains of Streptomyces, highlighting results from analysis of the recently sequenced Streptomyces coelicolor and Streptomyces avermitilis genomes. We address this question: Why is multiple secondary metabolite production in Streptomyces species so commonplace? We argue that synergy or contingency in the action of individual metabolites against biological competitors may, in some cases, be a powerful driving force for the evolution of multiple secondary metabolite production. This argument is illustrated with examples of the coproduction of synergistically acting antibiotics and contingently acting siderophores: two well-known classes of secondary metabolite. We focus, in particular, on the coproduction of β-lactam antibiotics and β-lactamase inhibitors, the coproduction of type A and type B streptogramins, and the coregulated production and independent uptake of structurally distinct siderophores by species of Streptomyces. Possible mechanisms for the evolution of multiple synergistic and contingent metabolite production in Streptomyces species are discussed. It is concluded that the production by Streptomyces species of two or more secondary metabolites that act synergistically or contingently against biological competitors may be far more common than has previously been recognized, and that synergy and contingency may be common driving forces for the evolution of multiple secondary metabolite production by these sessile saprophytes. PMID:12970466

Estimation of dimensions and orientation of multiple riverine dune generations using spectral moments

NASA Astrophysics Data System (ADS)

Lisimenka, Aliaksandr; Kubicki, Adam

2017-02-01

A new spectral analysis technique is proposed for rhythmic bedform quantification, based on the 2D Fourier transform involving the calculation of a set of low-order spectral moments. The approach provides a tool for efficient quantification of bedform length and height as well as spatial crest-line alignment. Contrary to the conventional method, it not only describes the most energetic component of an undulating seabed surface but also retrieves information on its secondary structure without application of any band-pass filter of which the upper and lower cut-off frequencies are a priori unknown. Validation is based on bathymetric data collected in the main Vistula River mouth area (Przekop Wisły), Poland. This revealed two generations (distinct groups) of dunes which are migrating seawards along distinct paths, probably related to the hydrological regime of the river. The data enable the identification of dune divergence and convergence zones. The approach proved successful in the parameterisation of topographic roughness, an essential aspect in numerical modelling studies.

How Many Pathways Underlie Socioeconomic Differences in the Development of Cognition and Achievement?

PubMed

Tucker-Drob, Elliot M

2013-06-01

Children whose parents have higher education enjoy greater age-linked gains in cognitive abilities and academic achievement. Different researchers have typically focused on different outcomes, and the extent to which parental education relates to multiple child outcomes via a single developmental pathway has received little empirical attention. This issue was examined by applying common factor structural equation models to a large (N = 4,810) nationally representative sample of kindergarten through 12 th grade children, who were measured on 6 distinct cognitive abilities and 5 distinct forms of knowledge and academic achievement. Results indicated that a single pathway accounted for the relations between parental education and age differences in children's cognitive abilities. However, additional unique pathways were necessary to account for the relations between parental education and age differences in academic knowledge and mathematics. These results suggest that while socioeconomic differences are largely manifest in global aspects of cognitive development, they have incremental relations with some forms of academic achievement.

Microsatellite markers identify three lineages of Phytophthora ramorum in US nurseries, yet single lineages in US forest and European nursery populations.

PubMed

Ivors, K; Garbelotto, M; Vries, I D E; Ruyter-Spira, C; Te Hekkert, B; Rosenzweig, N; Bonants, P

2006-05-01

Analysis of 12 polymorphic simple sequence repeats identified in the genome sequence of Phytophthora ramorum, causal agent of 'sudden oak death', revealed genotypic diversity to be significantly higher in nurseries (91% of total) than in forests (18% of total). Our analysis identified only two closely related genotypes in US forests, while the genetic structure of populations from European nurseries was of intermediate complexity, including multiple, closely related genotypes. Multilocus analysis determined populations in US forests reproduce clonally and are likely descendants of a single introduced individual. The 151 isolates analysed clustered in three clades. US forest and European nursery isolates clustered into two distinct clades, while one isolate from a US nursery belonged to a third novel clade. The combined microsatellite, sequencing and morphological analyses suggest the three clades represent distinct evolutionary lineages. All three clades were identified in some US nurseries, emphasizing the role of commercial plant trade in the movement of this pathogen.

Odour dialects among wild mammals.

PubMed

Kean, Eleanor Freya; Bruford, Michael William; Russo, Isa-Rita M; Müller, Carsten Theodor; Chadwick, Elizabeth Anna

2017-10-19

Across multiple taxa, population structure and dynamics depend on effective signalling between individuals. Among mammals, chemical communication is arguably the most important sense, underpinning mate choice, parental care, territoriality and even disease transmission. There is a growing body of evidence that odours signal genetic information that may confer considerable benefits including inbreeding avoidance and nepotism. To date, however, there has been no clear evidence that odours encode population-level information in wild mammals. Here we demonstrate for the first time the existence of 'odour dialects' in genetically distinct mammalian subpopulations across a large geographical scale. We found that otters, Lutra lutra, from across the United Kingdom possess sex and biogeography-specific odours. Subpopulations with the most distinctive odour profiles are also the most genetically diverse but not the most genetically differentiated. Furthermore, geographic distance between individuals does not explain regional odour differences, refuting other potential explanations such as group odour sharing behaviour. Differences in the language of odours between subpopulations have the potential to affect individual interactions, which could impact reproduction and gene-flow.

Characterization of Ventilatory Modes in Dragonfly Nymph

NASA Astrophysics Data System (ADS)

Roh, Chris; Saxton-Fox, Theresa; Gharib, Morteza

2013-11-01

A dragonfly nymph's highly modified hindgut has multiple ventilatory modes: hyperventilation (i.e. jet propulsion), gulping ventilation (extended expiratory phase) and normal ventilation. Each mode involves dynamic manipulation of the exit diameter and pressure. To study the different fluid dynamics associated with the three modes, Anisopteran larvae of the family Aeshnidae were tethered onto a rod for flow visualization. The result showed distinct flow structures. The hyperventilation showed a highly turbulent and powerful jet that occurred at high frequency. The gulping ventilation produced a single vortex at a moderate frequency. The normal ventilation showed two distinct vortices, a low-Reynolds number vortex, followed by a high-Reynolds number vortex. Furthermore, a correlation of the formation of the vortices with the movement of the sternum showed that the dragonfly is actively controlling the timing and the speed of the vortices to have them at equal distance from the jet exit at the onset of inspiration. This behavior prevents inspiration of the oxygen deficient expirated water, resulting in the maximization of the oxygen intake. Supported by NSF GRFP.

Distinct aspects of frontal lobe structure mediate age-related differences in fluid intelligence and multitasking

PubMed Central

Kievit, Rogier A.; Davis, Simon W.; Mitchell, Daniel J.; Taylor, Jason R.; Duncan, John; Tyler, Lorraine K.; Brayne, Carol; Bullmore, Ed; Calder, Andrew; Cusack, Rhodri; Dalgleish, Tim; Matthews, Fiona; Marslen-Wilson, William; Rowe, James; Shafto, Meredith; Campbell, Karen; Cheung, Teresa; Geerligs, Linda; McCarrey, Anna; Tsvetanov, Kamen; Williams, Nitin; Bates, Lauren; Emery, Tina; Erzinçlioglu, Sharon; Gadie, Andrew; Gerbase, Sofia; Georgieva, Stanimira; Hanley, Claire; Parkin, Beth; Troy, David; Allen, Jodie; Amery, Gillian; Amunts, Liana; Barcroft, Anne; Castle, Amanda; Dias, Cheryl; Dowrick, Jonathan; Fair, Melissa; Fisher, Hayley; Goulding, Anna; Grewal, Adarsh; Hale, Geoff; Hilton, Andrew; Johnson, Frances; Johnston, Patricia; Kavanagh-Williamson, Thea; Kwasniewska, Magdalena; McMinn, Alison; Norman, Kim; Penrose, Jessica; Roby, Fiona; Rowland, Diane; Sargeant, John; Squire, Maggie; Stevens, Beth; Stoddart, Aldabra; Stone, Cheryl; Thompson, Tracy; Yazlik, Ozlem; Barnes, Dan; Dixon, Marie; Hillman, Jaya; Mitchell, Joanne; Villis, Laura; Henson, Richard N.A.

2014-01-01

Ageing is characterized by declines on a variety of cognitive measures. These declines are often attributed to a general, unitary underlying cause, such as a reduction in executive function owing to atrophy of the prefrontal cortex. However, age-related changes are likely multifactorial, and the relationship between neural changes and cognitive measures is not well-understood. Here we address this in a large (N=567), population-based sample drawn from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data. We relate fluid intelligence and multitasking to multiple brain measures, including grey matter in various prefrontal regions and white matter integrity connecting those regions. We show that multitasking and fluid intelligence are separable cognitive abilities, with differential sensitivities to age, which are mediated by distinct neural subsystems that show different prediction in older versus younger individuals. These results suggest that prefrontal ageing is a manifold process demanding multifaceted models of neurocognitive ageing. PMID:25519467

The synthetic diazonamide DZ-2384 has distinct effects on microtubule curvature and dynamics without neurotoxicity

PubMed Central

Wieczorek, Michal; Tcherkezian, Joseph; Bernier, Cynthia; Prota, Andrea E.; Chaaban, Sami; Rolland, Yannève; Godbout, Claude; Hancock, Mark A.; Arezzo, Joseph C.; Ocal, Ozhan; Rocha, Cecilia; Olieric, Natacha; Hall, Anita; Ding, Hui; Bramoullé, Alexandre; Annis, Matthew G.; Zogopoulos, George; Harran, Patrick G.; Wilkie, Thomas M.; Brekken, Rolf A.; Siegel, Peter M.; Steinmetz, Michel O.; Shore, Gordon C.; Brouhard, Gary J.; Roulston, Anne

2017-01-01

Microtubule-targeting agents (MTAs) are widely used anticancer agents, but toxicities such as neuropathy limit their clinical use. MTAs bind to and alter the stability of microtubules, causing cell death in mitosis. We describe DZ-2384, a preclinical compound that exhibits potent antitumor activity in models of multiple cancer types. It has an unusually high safety margin and lacks neurotoxicity in rats at effective plasma concentrations. DZ-2384 binds the vinca domain of tubulin in a distinct way, imparting structurally and functionally different effects on microtubule dynamics compared to other vinca-binding compounds. X-ray crystallography and electron microscopy studies demonstrate that DZ-2384 causes straightening of curved protofilaments, an effect proposed to favor polymerization of tubulin. Both DZ-2384 and the vinca alkaloid vinorelbine inhibit microtubule growth rate; however, DZ-2384 increases the rescue frequency and preserves the microtubule network in nonmitotic cells and in primary neurons. This differential modulation of tubulin results in a potent MTA therapeutic with enhanced safety. PMID:27856798

Multiple sclerosis and human T-cell lymphotropic retroviruses

NASA Astrophysics Data System (ADS)

Koprowski, Hilary; Defreitas, Elaine C.; Harper, Mary E.; Sandberg-Wollheim, Magnhild; Sheremata, William A.; Robert-Guroff, Marjorie; Saxinger, Carl W.; Feinberg, Mark B.; Wong-Staal, Flossie; Gallo, Robert C.

1985-11-01

A combination of different types of data suggests that some multiple sclerosis patients respond immunologically to, and have cerebrospinal T cells containing, a retrovirus that is related to, but distinct from, the three types of human T-cell lymphotropic viruses. The role of this virus in multiple sclerosis is uncertain.

Structural basis for activation of trimeric Gi proteins by multiple growth factor receptors via GIV/Girdin

PubMed Central

Lin, Changsheng; Ear, Jason; Midde, Krishna; Lopez-Sanchez, Inmaculada; Aznar, Nicolas; Garcia-Marcos, Mikel; Kufareva, Irina; Abagyan, Ruben; Ghosh, Pradipta

2014-01-01

A long-standing issue in the field of signal transduction is to understand the cross-talk between receptor tyrosine kinases (RTKs) and heterotrimeric G proteins, two major and distinct signaling hubs that control eukaryotic cell behavior. Although stimulation of many RTKs leads to activation of trimeric G proteins, the molecular mechanisms behind this phenomenon remain elusive. We discovered a unifying mechanism that allows GIV/Girdin, a bona fide metastasis-related protein and a guanine-nucleotide exchange factor (GEF) for Gαi, to serve as a direct platform for multiple RTKs to activate Gαi proteins. Using a combination of homology modeling, protein–protein interaction, and kinase assays, we demonstrate that a stretch of ∼110 amino acids within GIV C-terminus displays structural plasticity that allows folding into a SH2-like domain in the presence of phosphotyrosine ligands. Using protein–protein interaction assays, we demonstrated that both SH2 and GEF domains of GIV are required for the formation of a ligand-activated ternary complex between GIV, Gαi, and growth factor receptors and for activation of Gαi after growth factor stimulation. Expression of a SH2-deficient GIV mutant (Arg 1745→Leu) that cannot bind RTKs impaired all previously demonstrated functions of GIV—Akt enhancement, actin remodeling, and cell migration. The mechanistic and structural insights gained here shed light on the long-standing questions surrounding RTK/G protein cross-talk, set a novel paradigm, and characterize a unique pharmacological target for uncoupling GIV-dependent signaling downstream of multiple oncogenic RTKs. PMID:25187647

Electret Acoustic Transducer Array For Computerized Ultrasound Risk Evaluation System

DOEpatents

Moore, Thomas L.; Fisher, Karl A.

2005-08-09

An electret-based acoustic transducer array is provided and may be used in a system for examining tissue. The acoustic transducer array is formed with a substrate that has a multiple distinct cells formed therein. Within each of the distinct cells is positioned an acoustic transducing element formed of an electret material. A conductive membrane is formed over the distinct cells and may be flexible.

Overlap and distinctiveness of psychological risk factors in patients with ischemic heart disease and chronic heart failure: are we there yet?

PubMed

Pelle, Aline J; Denollet, Johan; Zwisler, Ann-Dorthe; Pedersen, Susanne S

2009-02-01

Growing evidence supports the importance of psychological factors in the etiology and progression of cardiovascular disease (CVD). However, this research has been criticized due to overlap between psychological constructs. We examined whether psychological questionnaires frequently used in cardiovascular research assess distinct constructs in a mixed group of ischemic heart disease (IHD) and chronic heart failure (CHF) patients. 565 patients with CHF (n=118) or IHD (n=447) completed the Type D scale (DS14), Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory (BDI), and State Trait Anxiety Inventory (STAI). Pearson product moment correlations were computed to determine the interrelatedness between psychological constructs. Principal component analyses (PCA) were conducted on both scale scores and items to determine higher-order constructs and distinctiveness of psychological questionnaires. Two higher-order constructs were identified, namely negative affect and social inhibition. PCA on all 69 items showed that anxiety, depression, negative affectivity, and social inhibition were distinct constructs. The original structure of the DS14 was confirmed, whereas items of the HADS and BDI loaded more diffusely; items of the STAI reflected two different components. The use of multiple questionnaires in cardiac patients is justified, as the higher order construct negative affect comprised different facets. Social inhibition was also shown to be a distinct construct, indicating that it may timely for cardiovascular research to look at the role of inhibition in addition to negative emotions. Future studies are warranted to determine whether these findings are replicable in other cardiac samples and to specify the unique prognostic value of these psychological facets.

Whole Genome Sequence Typing to Investigate the Apophysomyces Outbreak following a Tornado in Joplin, Missouri, 2011

PubMed Central

Etienne, Kizee A.; Gillece, John; Hilsabeck, Remy; Schupp, Jim M.; Colman, Rebecca; Lockhart, Shawn R.; Gade, Lalitha; Thompson, Elizabeth H.; Sutton, Deanna A.; Neblett-Fanfair, Robyn; Park, Benjamin J.; Turabelidze, George; Keim, Paul; Brandt, Mary E.; Deak, Eszter; Engelthaler, David M.

2012-01-01

Case reports of Apophysomyces spp. in immunocompetent hosts have been a result of traumatic deep implantation of Apophysomyces spp. spore-contaminated soil or debris. On May 22, 2011 a tornado occurred in Joplin, MO, leaving 13 tornado victims with Apophysomyces trapeziformis infections as a result of lacerations from airborne material. We used whole genome sequence typing (WGST) for high-resolution phylogenetic SNP analysis of 17 outbreak Apophysomyces isolates and five additional temporally and spatially diverse Apophysomyces control isolates (three A. trapeziformis and two A. variabilis isolates). Whole genome SNP phylogenetic analysis revealed three clusters of genotypically related or identical A. trapeziformis isolates and multiple distinct isolates among the Joplin group; this indicated multiple genotypes from a single or multiple sources. Though no linkage between genotype and location of exposure was observed, WGST analysis determined that the Joplin isolates were more closely related to each other than to the control isolates, suggesting local population structure. Additionally, species delineation based on WGST demonstrated the need to reassess currently accepted taxonomic classifications of phylogenetic species within the genus Apophysomyces. PMID:23209631

Whole genome sequence typing to investigate the Apophysomyces outbreak following a tornado in Joplin, Missouri, 2011.

PubMed

Etienne, Kizee A; Gillece, John; Hilsabeck, Remy; Schupp, Jim M; Colman, Rebecca; Lockhart, Shawn R; Gade, Lalitha; Thompson, Elizabeth H; Sutton, Deanna A; Neblett-Fanfair, Robyn; Park, Benjamin J; Turabelidze, George; Keim, Paul; Brandt, Mary E; Deak, Eszter; Engelthaler, David M

2012-01-01

Case reports of Apophysomyces spp. in immunocompetent hosts have been a result of traumatic deep implantation of Apophysomyces spp. spore-contaminated soil or debris. On May 22, 2011 a tornado occurred in Joplin, MO, leaving 13 tornado victims with Apophysomyces trapeziformis infections as a result of lacerations from airborne material. We used whole genome sequence typing (WGST) for high-resolution phylogenetic SNP analysis of 17 outbreak Apophysomyces isolates and five additional temporally and spatially diverse Apophysomyces control isolates (three A. trapeziformis and two A. variabilis isolates). Whole genome SNP phylogenetic analysis revealed three clusters of genotypically related or identical A. trapeziformis isolates and multiple distinct isolates among the Joplin group; this indicated multiple genotypes from a single or multiple sources. Though no linkage between genotype and location of exposure was observed, WGST analysis determined that the Joplin isolates were more closely related to each other than to the control isolates, suggesting local population structure. Additionally, species delineation based on WGST demonstrated the need to reassess currently accepted taxonomic classifications of phylogenetic species within the genus Apophysomyces.

Distinct organization of the candidate tumor suppressor gene RFP2 in human and mouse: multiple mRNA isoforms in both species- and human-specific antisense transcript RFP2OS.

PubMed

Baranova, Ancha; Hammarsund, Marianne; Ivanov, Dmitry; Skoblov, Mikhail; Sangfelt, Olle; Corcoran, Martin; Borodina, Tatiana; Makeeva, Natalia; Pestova, Anna; Tyazhelova, Tatiana; Nazarenko, Svetlana; Gorreta, Francesco; Alsheddi, Tariq; Schlauch, Karen; Nikitin, Eugene; Kapanadze, Bagrat; Shagin, Dmitry; Poltaraus, Andrey; Ivanovich Vorobiev, Andrey; Zabarovsky, Eugene; Lukianov, Sergey; Chandhoke, Vikas; Ibbotson, Rachel; Oscier, David; Einhorn, Stefan; Grander, Dan; Yankovsky, Nick

2003-12-04

In the present study, we describe the human and mouse RFP2 gene structure, multiple RFP2 mRNA isoforms in the two species that have different 5' UTRs and a human-specific antisense transcript RFP2OS. Since the human RFP2 5' UTR is not conserved in mouse, these findings might indicate a different regulation of RFP2 in the two species. The predicted human and mouse RFP2 proteins are shown to contain a tripartite RING finger-B-box-coiled-coil domain (RBCC), also known as a TRIM domain, and therefore belong to a subgroup of RING finger proteins that are often involved in developmental and tumorigenic processes. Because homozygous deletions of chromosomal region 13q14.3 are found in a number of malignancies, including chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), we suggest that RFP2 might be involved in tumor development. This study provides necessary information for evaluation of the role of RFP2 in malignant transformation and other biological processes.

Amyloid oligomer structure characterization from simulations: A general method

NASA Astrophysics Data System (ADS)

Nguyen, Phuong H.; Li, Mai Suan; Derreumaux, Philippe

2014-03-01

Amyloid oligomers and plaques are composed of multiple chemically identical proteins. Therefore, one of the first fundamental problems in the characterization of structures from simulations is the treatment of the degeneracy, i.e., the permutation of the molecules. Second, the intramolecular and intermolecular degrees of freedom of the various molecules must be taken into account. Currently, the well-known dihedral principal component analysis method only considers the intramolecular degrees of freedom, and other methods employing collective variables can only describe intermolecular degrees of freedom at the global level. With this in mind, we propose a general method that identifies all the structures accurately. The basis idea is that the intramolecular and intermolecular states are described in terms of combinations of single-molecule and double-molecule states, respectively, and the overall structures of oligomers are the product basis of the intramolecular and intermolecular states. This way, the degeneracy is automatically avoided. The method is illustrated on the conformational ensemble of the tetramer of the Alzheimer's peptide Aβ9-40, resulting from two atomistic molecular dynamics simulations in explicit solvent, each of 200 ns, starting from two distinct structures.

Computed Energetics of Nucleotides in Spatial Ribozyme Structures: An Accurate Identification of Functional Regions from Structure

PubMed Central

Torshin, Ivan Y.

2004-01-01

Ribozymes are functionally diverse RNA molecules with intrinsic catalytic activity. Multiple structural and biochemical studies are required to establish which nucleotide bases are involved in the catalysis. The relative energetic properties of the nucleotide bases have been analyzed in a set of the known ribozyme structures. It was found that many of the known catalytic nucleotides can be identified using only the structure without any additional biochemical data. The results of the calculations compare well with the available biochemical data on RNA stability. Extensive in silico mutagenesis suggests that most of the nucleotides in ribozymes stabilize the RNA. The calculations show that relative contribution of the catalytic bases to RNA stability observably differs from contributions of the noncatalytic bases. Distinction between the concepts of “relative stability” and “mutational stability” is suggested. As results of prediction for several models of ribozymes appear to be in agreement with the published data on the potential active site regions, the method can potentially be used for prediction of functional nucleotides from nucleic sequence. PMID:15105962

The Episodic Memory System: Neurocircuitry and Disorders

PubMed Central

Dickerson, Bradford C; Eichenbaum, Howard

2010-01-01

The ability to encode and retrieve our daily personal experiences, called episodic memory, is supported by the circuitry of the medial temporal lobe (MTL), including the hippocampus, which interacts extensively with a number of specific distributed cortical and subcortical structures. In both animals and humans, evidence from anatomical, neuropsychological, and physiological studies indicates that cortical components of this system have key functions in several aspects of perception and cognition, whereas the MTL structures mediate the organization and persistence of the network of memories whose details are stored in those cortical areas. Structures within the MTL, and particularly the hippocampus, have distinct functions in combining information from multiple cortical streams, supporting our ability to encode and retrieve details of events that compose episodic memories. Conversely, selective damage in the hippocampus, MTL, and other structures of the large-scale memory system, or deterioration of these areas in several diseases and disorders, compromises episodic memory. A growing body of evidence is converging on a functional organization of the cortical, subcortical, and MTL structures that support the fundamental features of episodic memory in humans and animals. PMID:19776728

Classification of epilepsy types through global network analysis of scalp electroencephalograms

NASA Astrophysics Data System (ADS)

Lee, Uncheol; Kim, Seunghwan; Jung, Ki-Young

2006-04-01

Epilepsy is a dynamic disease in which self-organization and emergent structures occur dynamically at multiple levels of neuronal integration. Therefore, the transient relationship within multichannel electroencephalograms (EEGs) is crucial for understanding epileptic processes. In this paper, we show that the global relationship within multichannel EEGs provides us with more useful information in classifying two different epilepsy types than pairwise relationships such as cross correlation. To demonstrate this, we determine the global network structure within channels of the scalp EEG based on the minimum spanning tree method. The topological dissimilarity of the network structures from different types of temporal lobe epilepsy is described in the form of the divergence rate and is computed for 11 patients with left (LTLE) and right temporal lobe epilepsy (RTLE). We find that patients with LTLE and RTLE exhibit different large scale network structures, which emerge at the epoch immediately before the seizure onset, not in the preceding epochs. Our results suggest that patients with the two different epilepsy types display distinct large scale dynamical networks with characteristic epileptic network structures.

DNA methylation analysis of phenotype specific stratified Indian population.

PubMed

Rotti, Harish; Mallya, Sandeep; Kabekkodu, Shama Prasada; Chakrabarty, Sanjiban; Bhale, Sameer; Bharadwaj, Ramachandra; Bhat, Balakrishna K; Dedge, Amrish P; Dhumal, Vikram Ram; Gangadharan, G G; Gopinath, Puthiya M; Govindaraj, Periyasamy; Joshi, Kalpana S; Kondaiah, Paturu; Nair, Sreekumaran; Nair, S N Venugopalan; Nayak, Jayakrishna; Prasanna, B V; Shintre, Pooja; Sule, Mayura; Thangaraj, Kumarasamy; Patwardhan, Bhushan; Valiathan, Marthanda Varma Sankaran; Satyamoorthy, Kapaettu

2015-05-08

DNA methylation and its perturbations are an established attribute to a wide spectrum of phenotypic variations and disease conditions. Indian traditional system practices personalized medicine through indigenous concept of distinctly descriptive physiological, psychological and anatomical features known as prakriti. Here we attempted to establish DNA methylation differences in these three prakriti phenotypes. Following structured and objective measurement of 3416 subjects, whole blood DNA of 147 healthy male individuals belonging to defined prakriti (Vata, Pitta and Kapha) between the age group of 20-30years were subjected to methylated DNA immunoprecipitation (MeDIP) and microarray analysis. After data analysis, prakriti specific signatures were validated through bisulfite DNA sequencing. Differentially methylated regions in CpG islands and shores were significantly enriched in promoters/UTRs and gene body regions. Phenotypes characterized by higher metabolism (Pitta prakriti) in individuals showed distinct promoter (34) and gene body methylation (204), followed by Vata prakriti which correlates to motion showed DNA methylation in 52 promoters and 139 CpG islands and finally individuals with structural attributes (Kapha prakriti) with 23 and 19 promoters and CpG islands respectively. Bisulfite DNA sequencing of prakriti specific multiple CpG sites in promoters and 5'-UTR such as; LHX1 (Vata prakriti), SOX11 (Pitta prakriti) and CDH22 (Kapha prakriti) were validated. Kapha prakriti specific CDH22 5'-UTR CpG methylation was also found to be associated with higher body mass index (BMI). Differential DNA methylation signatures in three distinct prakriti phenotypes demonstrate the epigenetic basis of Indian traditional human classification which may have relevance to personalized medicine.

Overlapping and Divergent Actions of Structurally Distinct Histone Deacetylase Inhibitors in Cardiac Fibroblasts

PubMed Central

Schuetze, Katherine B.; Stratton, Matthew S.; Blakeslee, Weston W.; Wempe, Michael F.; Wagner, Florence F.; Holson, Edward B.; Kuo, Yin-Ming; Andrews, Andrew J.; Gilbert, Tonya M.; Hooker, Jacob M.

2017-01-01

Inhibitors of zinc-dependent histone deacetylases (HDACs) profoundly affect cellular function by altering gene expression via changes in nucleosomal histone tail acetylation. Historically, investigators have employed pan-HDAC inhibitors, such as the hydroxamate trichostatin A (TSA), which simultaneously targets members of each of the three zinc-dependent HDAC classes (classes I, II, and IV). More recently, class- and isoform-selective HDAC inhibitors have been developed, providing invaluable chemical biology probes for dissecting the roles of distinct HDACs in the control of various physiologic and pathophysiological processes. For example, the benzamide class I HDAC-selective inhibitor, MGCD0103 [N-(2-aminophenyl)-4-[[(4-pyridin-3-ylpyrimidin-2-yl)amino]methyl] benzamide], was shown to block cardiac fibrosis, a process involving excess extracellular matrix deposition, which often results in heart dysfunction. Here, we compare the mechanisms of action of structurally distinct HDAC inhibitors in isolated primary cardiac fibroblasts, which are the major extracellular matrix–producing cells of the heart. TSA, MGCD0103, and the cyclic peptide class I HDAC inhibitor, apicidin, exhibited a common ability to enhance histone acetylation, and all potently blocked cardiac fibroblast cell cycle progression. In contrast, MGCD0103, but not TSA or apicidin, paradoxically increased expression of a subset of fibrosis-associated genes. Using the cellular thermal shift assay, we provide evidence that the divergent effects of HDAC inhibitors on cardiac fibroblast gene expression relate to differential engagement of HDAC1- and HDAC2-containing complexes. These findings illustrate the importance of employing multiple compounds when pharmacologically assessing HDAC function in a cellular context and during HDAC inhibitor drug development. PMID:28174211

Self-organization of a periodic structure between amorphous and crystalline phases in a GeTe thin film induced by femtosecond laser pulse amorphization

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

Katsumata, Y.; Morita, T.; Morimoto, Y.

A self-organized fringe pattern in a single amorphous mark of a GeTe thin film was formed by multiple femtosecond pulse amorphization. Micro Raman measurement indicates that the fringe is a periodic alternation between crystalline and amorphous phases. The period of the fringe is smaller than the irradiation wavelength and the direction is parallel to the polarization direction. Snapshot observation revealed that the fringe pattern manifests itself via a complex but coherent process, which is attributed to crystallization properties unique to a nonthermally amorphized phase and the distinct optical contrast between crystalline and amorphous phases.

Geographic Population Structure in Epstein-Barr Virus Revealed by Comparative Genomics

PubMed Central

Chiara, Matteo; Manzari, Caterina; Lionetti, Claudia; Mechelli, Rosella; Anastasiadou, Eleni; Chiara Buscarinu, Maria; Ristori, Giovanni; Salvetti, Marco; Picardi, Ernesto; D’Erchia, Anna Maria; Pesole, Graziano; Horner, David S.

2016-01-01

Epstein-Barr virus (EBV) latently infects the majority of the human population and is implicated as a causal or contributory factor in numerous diseases. We sequenced 27 complete EBV genomes from a cohort of Multiple Sclerosis (MS) patients and healthy controls from Italy, although no variants showed a statistically significant association with MS. Taking advantage of the availability of ∼130 EBV genomes with known geographical origins, we reveal a striking geographic distribution of EBV sub-populations with distinct allele frequency distributions. We discuss mechanisms that potentially explain these observations, and their implications for understanding the association of EBV with human disease. PMID:27635051

Node-Based Learning of Multiple Gaussian Graphical Models

PubMed Central

Mohan, Karthik; London, Palma; Fazel, Maryam; Witten, Daniela; Lee, Su-In

2014-01-01

We consider the problem of estimating high-dimensional Gaussian graphical models corresponding to a single set of variables under several distinct conditions. This problem is motivated by the task of recovering transcriptional regulatory networks on the basis of gene expression data containing heterogeneous samples, such as different disease states, multiple species, or different developmental stages. We assume that most aspects of the conditional dependence networks are shared, but that there are some structured differences between them. Rather than assuming that similarities and differences between networks are driven by individual edges, we take a node-based approach, which in many cases provides a more intuitive interpretation of the network differences. We consider estimation under two distinct assumptions: (1) differences between the K networks are due to individual nodes that are perturbed across conditions, or (2) similarities among the K networks are due to the presence of common hub nodes that are shared across all K networks. Using a row-column overlap norm penalty function, we formulate two convex optimization problems that correspond to these two assumptions. We solve these problems using an alternating direction method of multipliers algorithm, and we derive a set of necessary and sufficient conditions that allows us to decompose the problem into independent subproblems so that our algorithm can be scaled to high-dimensional settings. Our proposal is illustrated on synthetic data, a webpage data set, and a brain cancer gene expression data set. PMID:25309137

Genetically distinct populations of northern shrimp, Pandalus borealis, in the North Atlantic: adaptation to different temperatures as an isolation factor.

PubMed

Jorde, Per Erik; Søvik, Guldborg; Westgaard, Jon-Ivar; Albretsen, Jon; André, Carl; Hvingel, Carsten; Johansen, Torild; Sandvik, Anne Dagrun; Kingsley, Michael; Jørstad, Knut Eirik

2015-04-01

The large-scale population genetic structure of northern shrimp, Pandalus borealis, was investigated over the species' range in the North Atlantic, identifying multiple genetically distinct groups. Genetic divergence among sample localities varied among 10 microsatellite loci (range: FST = -0.0002 to 0.0475) with a highly significant average (FST = 0.0149; P < 0.0001). In contrast, little or no genetic differences were observed among temporal replicates from the same localities (FST = 0.0004; P = 0.33). Spatial genetic patterns were compared to geographic distances, patterns of larval drift obtained through oceanographic modelling, and temperature differences, within a multiple linear regression framework. The best-fit model included all three factors and explained approximately 29% of all spatial genetic divergence. However, geographic distance and larval drift alone had only minor effects (2.5-4.7%) on large-scale genetic differentiation patterns, whereas bottom temperature differences explained most (26%). Larval drift was found to promote genetic homogeneity in parts of the study area with strong currents, but appeared ineffective across large temperature gradients. These findings highlight the breakdown of gene flow in a species with a long pelagic larval phase (up to 3 months) and indicate a role for local adaptation to temperature conditions in promoting evolutionary diversification and speciation in the marine environment. © 2015 John Wiley & Sons Ltd.

Numerical investigation on the dynamics and evolution mechanisms of multiple-current-pulse behavior in homogeneous helium dielectric-barrier discharges at atmospheric pressure

NASA Astrophysics Data System (ADS)

Zhang, Yuhui; Ning, Wenjun; Dai, Dong

2018-03-01

A systematic investigation on the dynamics and evolution mechanisms of multiple-current-pulse (MCP) behavior in homogeneous dielectric barrier discharge (HDBD) is carried out via fluid modelling. Inspecting the simulation results, two typical discharge regimes, namely the MCP-Townsend regime and MCP-glow regime, are found prevailing in MCP discharges, each with distinctive electrical and dynamic properties. Moreover, the evolution of MCP behavior with external parameters altering are illustrated and explicitly discussed. It is revealed that the discharge undergoes some different stages as external parameters vary, and the discharge in each stage follows a series of distinctive pattern in morphological characteristics and evolution trends. Among those stages, the pulse number per half cycle is perceived to observe non-monotonic variations with applied voltage amplitude (Vam) and gap width (dg) increasing, and a merging effect among pulses, mainly induced by the enhanced contribution of sinusoidal component to the total current, is considered responsible for such phenomenon. The variation of incipient discharge peak phase (Φpm) is dominated by the value of Vam as well as the proportion of total applied voltage that drops across the gas gap. Moreover, an abnormal, dramatic elevation in Jpm with dg increasing is observed, which could be evinced by the strengthened glow discharge structure and therefore enhanced space charge effect.

Characterizing complex structural variation in germline and somatic genomes

PubMed Central

Quinlan, Aaron R.; Hall, Ira M.

2011-01-01

Genome structural variation (SV) is a major source of genetic diversity in mammals and a hallmark of cancer. While SV is typically defined by its canonical forms – duplication, deletion, insertion, inversion and translocation – recent breakpoint mapping studies have revealed a surprising number of “complex” variants that evade simple classification. Complex SVs are defined by clustered breakpoints that arose through a single mutation but cannot be explained by one simple end-joining or recombination event. Some complex variants exhibit profoundly complicated rearrangements between distinct loci from multiple chromosomes, while others involve more subtle alterations at a single locus. These diverse and unpredictable features present a challenge for SV mapping experiments. Here, we review current knowledge of complex SV in mammals, and outline techniques for identifying and characterizing complex variants using next-generation DNA sequencing. PMID:22094265

Atomic-level characterization of the structural dynamics of proteins.

PubMed

Shaw, David E; Maragakis, Paul; Lindorff-Larsen, Kresten; Piana, Stefano; Dror, Ron O; Eastwood, Michael P; Bank, Joseph A; Jumper, John M; Salmon, John K; Shan, Yibing; Wriggers, Willy

2010-10-15

Molecular dynamics (MD) simulations are widely used to study protein motions at an atomic level of detail, but they have been limited to time scales shorter than those of many biologically critical conformational changes. We examined two fundamental processes in protein dynamics--protein folding and conformational change within the folded state--by means of extremely long all-atom MD simulations conducted on a special-purpose machine. Equilibrium simulations of a WW protein domain captured multiple folding and unfolding events that consistently follow a well-defined folding pathway; separate simulations of the protein's constituent substructures shed light on possible determinants of this pathway. A 1-millisecond simulation of the folded protein BPTI reveals a small number of structurally distinct conformational states whose reversible interconversion is slower than local relaxations within those states by a factor of more than 1000.

The Curious Case of Orthographic Distinctiveness: Disruption of Categorical Processing

ERIC Educational Resources Information Center

McDaniel, Mark A.; Cahill, Michael J.; Bugg, Julie M.

2016-01-01

How does orthographic distinctiveness affect recall of structured (categorized) word lists? On one theory, enhanced item-specific information (e.g., more distinct encoding) in concert with robust relational information (e.g., categorical information) optimally supports free recall. This predicts that for categorically structured lists,…

Structure-guided statistical textural distinctiveness for salient region detection in natural images.

PubMed

Scharfenberger, Christian; Wong, Alexander; Clausi, David A

2015-01-01

We propose a simple yet effective structure-guided statistical textural distinctiveness approach to salient region detection. Our method uses a multilayer approach to analyze the structural and textural characteristics of natural images as important features for salient region detection from a scale point of view. To represent the structural characteristics, we abstract the image using structured image elements and extract rotational-invariant neighborhood-based textural representations to characterize each element by an individual texture pattern. We then learn a set of representative texture atoms for sparse texture modeling and construct a statistical textural distinctiveness matrix to determine the distinctiveness between all representative texture atom pairs in each layer. Finally, we determine saliency maps for each layer based on the occurrence probability of the texture atoms and their respective statistical textural distinctiveness and fuse them to compute a final saliency map. Experimental results using four public data sets and a variety of performance evaluation metrics show that our approach provides promising results when compared with existing salient region detection approaches.

Free energy minimization to predict RNA secondary structures and computational RNA design.

PubMed

Churkin, Alexander; Weinbrand, Lina; Barash, Danny

2015-01-01

Determining the RNA secondary structure from sequence data by computational predictions is a long-standing problem. Its solution has been approached in two distinctive ways. If a multiple sequence alignment of a collection of homologous sequences is available, the comparative method uses phylogeny to determine conserved base pairs that are more likely to form as a result of billions of years of evolution than by chance. In the case of single sequences, recursive algorithms that compute free energy structures by using empirically derived energy parameters have been developed. This latter approach of RNA folding prediction by energy minimization is widely used to predict RNA secondary structure from sequence. For a significant number of RNA molecules, the secondary structure of the RNA molecule is indicative of its function and its computational prediction by minimizing its free energy is important for its functional analysis. A general method for free energy minimization to predict RNA secondary structures is dynamic programming, although other optimization methods have been developed as well along with empirically derived energy parameters. In this chapter, we introduce and illustrate by examples the approach of free energy minimization to predict RNA secondary structures.

Using RNA Sequence and Structure for the Prediction of Riboswitch Aptamer: A Comprehensive Review of Available Software and Tools

PubMed Central

Antunes, Deborah; Jorge, Natasha A. N.; Caffarena, Ernesto R.; Passetti, Fabio

2018-01-01

RNA molecules are essential players in many fundamental biological processes. Prokaryotes and eukaryotes have distinct RNA classes with specific structural features and functional roles. Computational prediction of protein structures is a research field in which high confidence three-dimensional protein models can be proposed based on the sequence alignment between target and templates. However, to date, only a few approaches have been developed for the computational prediction of RNA structures. Similar to proteins, RNA structures may be altered due to the interaction with various ligands, including proteins, other RNAs, and metabolites. A riboswitch is a molecular mechanism, found in the three kingdoms of life, in which the RNA structure is modified by the binding of a metabolite. It can regulate multiple gene expression mechanisms, such as transcription, translation initiation, and mRNA splicing and processing. Due to their nature, these entities also act on the regulation of gene expression and detection of small metabolites and have the potential to helping in the discovery of new classes of antimicrobial agents. In this review, we describe software and web servers currently available for riboswitch aptamer identification and secondary and tertiary structure prediction, including applications. PMID:29403526

Genome-Wide Analysis of Oleosin Gene Family in 22 Tree Species: An Accelerator for Metabolic Engineering of BioFuel Crops and Agrigenomics Industrial Applications?

PubMed Central

2015-01-01

Abstract Trees contribute to enormous plant oil reserves because many trees contain 50%–80% of oil (triacylglycerols, TAGs) in the fruits and kernels. TAGs accumulate in subcellular structures called oil bodies/droplets, in which TAGs are covered by low-molecular-mass hydrophobic proteins called oleosins (OLEs). The OLEs/TAGs ratio determines the size and shape of intracellular oil bodies. There is a lack of comprehensive sequence analysis and structural information of OLEs among diverse trees. The objectives of this study were to identify OLEs from 22 tree species (e.g., tung tree, tea-oil tree, castor bean), perform genome-wide analysis of OLEs, classify OLEs, identify conserved sequence motifs and amino acid residues, and predict secondary and three-dimensional structures in tree OLEs and OLE subfamilies. Data mining identified 65 OLEs with perfect conservation of the “proline knot” motif (PX5SPX3P) from 19 trees. These OLEs contained >40% hydrophobic amino acid residues. They displayed similar properties and amino acid composition. Genome-wide phylogenetic analysis and multiple sequence alignment demonstrated that these proteins could be classified into five OLE subfamilies. There were distinct patterns of sequence conservation among the OLE subfamilies and within individual tree species. Computational modeling indicated that OLEs were composed of at least three α-helixes connected with short coils without any β-strand and that they exhibited distinct 3D structures and ligand binding sites. These analyses provide fundamental information in the similarity and specificity of diverse OLE isoforms within the same subfamily and among the different species, which should facilitate studying the structure-function relationship and identify critical amino acid residues in OLEs for metabolic engineering of tree TAGs. PMID:26258573

Genome-Wide Analysis of Oleosin Gene Family in 22 Tree Species: An Accelerator for Metabolic Engineering of BioFuel Crops and Agrigenomics Industrial Applications?

PubMed

Cao, Heping

2015-09-01

Trees contribute to enormous plant oil reserves because many trees contain 50%-80% of oil (triacylglycerols, TAGs) in the fruits and kernels. TAGs accumulate in subcellular structures called oil bodies/droplets, in which TAGs are covered by low-molecular-mass hydrophobic proteins called oleosins (OLEs). The OLEs/TAGs ratio determines the size and shape of intracellular oil bodies. There is a lack of comprehensive sequence analysis and structural information of OLEs among diverse trees. The objectives of this study were to identify OLEs from 22 tree species (e.g., tung tree, tea-oil tree, castor bean), perform genome-wide analysis of OLEs, classify OLEs, identify conserved sequence motifs and amino acid residues, and predict secondary and three-dimensional structures in tree OLEs and OLE subfamilies. Data mining identified 65 OLEs with perfect conservation of the "proline knot" motif (PX5SPX3P) from 19 trees. These OLEs contained >40% hydrophobic amino acid residues. They displayed similar properties and amino acid composition. Genome-wide phylogenetic analysis and multiple sequence alignment demonstrated that these proteins could be classified into five OLE subfamilies. There were distinct patterns of sequence conservation among the OLE subfamilies and within individual tree species. Computational modeling indicated that OLEs were composed of at least three α-helixes connected with short coils without any β-strand and that they exhibited distinct 3D structures and ligand binding sites. These analyses provide fundamental information in the similarity and specificity of diverse OLE isoforms within the same subfamily and among the different species, which should facilitate studying the structure-function relationship and identify critical amino acid residues in OLEs for metabolic engineering of tree TAGs.

Metal ions may suppress or enhance cellular differentiation in Candida albicans and Candida tropicalis biofilms.

PubMed

Harrison, Joe J; Ceri, Howard; Yerly, Jerome; Rabiei, Maryam; Hu, Yaoping; Martinuzzi, Robert; Turner, Raymond J

2007-08-01

Candida albicans and Candida tropicalis are polymorphic fungi that develop antimicrobial-resistant biofilm communities that are characterized by multiple cell morphotypes. This study investigated cell type interconversion and drug and metal resistance as well as community organization in biofilms of these microorganisms that were exposed to metal ions. To study this, Candida biofilms were grown either in microtiter plates containing gradient arrays of metal ions or in the Calgary Biofilm Device for high-throughput susceptibility testing. Biofilm formation and antifungal resistance were evaluated by viable cell counts, tetrazolium salt reduction, light microscopy, and confocal laser scanning microscopy in conjunction with three-dimensional visualization. We discovered that subinhibitory concentrations of certain metal ions (CrO(4)(2-), Co(2+), Cu(2+), Ag(+), Zn(2+), Cd(2+), Hg(2+), Pb(2+), AsO(2)(-), and SeO(3)(2-)) caused changes in biofilm structure by blocking or eliciting the transition between yeast and hyphal cell types. Four distinct biofilm community structure types were discerned from these data, which were designated "domed," "layer cake," "flat," and "mycelial." This study suggests that Candida biofilm populations may respond to metal ions to form cell-cell and solid-surface-attached assemblages with distinct patterns of cellular differentiation.

Distinct Amino Acid Compositional Requirements for Formation and Maintenance of the [PSI+] Prion in Yeast

PubMed Central

MacLea, Kyle S.; Paul, Kacy R.; Ben-Musa, Zobaida; Waechter, Aubrey; Shattuck, Jenifer E.; Gruca, Margaret

2014-01-01

Multiple yeast prions have been identified that result from the structural conversion of proteins into a self-propagating amyloid form. Amyloid-based prion activity in yeast requires a series of discrete steps. First, the prion protein must form an amyloid nucleus that can recruit and structurally convert additional soluble proteins. Subsequently, maintenance of the prion during cell division requires fragmentation of these aggregates to create new heritable propagons. For the Saccharomyces cerevisiae prion protein Sup35, these different activities are encoded by different regions of the Sup35 prion domain. An N-terminal glutamine/asparagine-rich nucleation domain is required for nucleation and fiber growth, while an adjacent oligopeptide repeat domain is largely dispensable for prion nucleation and fiber growth but is required for chaperone-dependent prion maintenance. Although prion activity of glutamine/asparagine-rich proteins is predominantly determined by amino acid composition, the nucleation and oligopeptide repeat domains of Sup35 have distinct compositional requirements. Here, we quantitatively define these compositional requirements in vivo. We show that aromatic residues strongly promote both prion formation and chaperone-dependent prion maintenance. In contrast, nonaromatic hydrophobic residues strongly promote prion formation but inhibit prion propagation. These results provide insight into why some aggregation-prone proteins are unable to propagate as prions. PMID:25547291

Autoantigens in systemic autoimmunity: critical partner in pathogenesis

PubMed Central

Rosen, A.; Casciola-Rosen, L.

2013-01-01

Understanding the mechanisms of human autoimmune rheumatic diseases presents a major challenge, due to marked complexity involving multiple domains, including genetics, environment and kinetics. In spite of this, the immune response in each of these diseases is largely specific, with distinct autoantibodies associated with different disease phenotypes. Defining the basis of such specificity will provide important insights into disease mechanism. Accumulating data suggest an interesting paradigm for antigen selection in autoimmunity, in which target tissue and immune effector pathways form a mutually reinforcing partnership. In this model, distinct autoantibody patterns in autoimmunity may be viewed as the integrated, amplified output of several interacting systems, including: (i) the specific target tissue, (ii) the immune effector pathways that modify antigen structure and cause tissue damage and dysfunction, and (iii) the homeostatic pathways activated in response to damage (e.g. regeneration/differentiation/cytokine effects). As unique antigen expression and structure may occur exclusively under these amplifying circumstances, it is useful to view the molecules targeted as ‘neo-antigens’, that is, antigens expressed under specific conditions, rather than ubiquitously. This model adds an important new dynamic element to selection of antigen targets in autoimmunity, and suggests that the amplifying loop will only be identified by studying the diseased target tissue in vivo. PMID:19493056

Two ribosome recruitment sites direct multiple translation events within HIV1 Gag open reading frame.

PubMed

Deforges, Jules; de Breyne, Sylvain; Ameur, Melissa; Ulryck, Nathalie; Chamond, Nathalie; Saaidi, Afaf; Ponty, Yann; Ohlmann, Theophile; Sargueil, Bruno

2017-07-07

In the late phase of the HIV virus cycle, the unspliced genomic RNA is exported to the cytoplasm for the necessary translation of the Gag and Gag-pol polyproteins. Three distinct translation initiation mechanisms ensuring Gag production have been described with little rationale for their multiplicity. The Gag-IRES has the singularity to be located within Gag ORF and to directly interact with ribosomal 40S. Aiming at elucidating the specificity and the relevance of this interaction, we probed HIV-1 Gag-IRES structure and developed an innovative integrative modelling strategy to take into account all the gathered information. We propose a novel Gag-IRES secondary structure strongly supported by all experimental data. We further demonstrate the presence of two regions within Gag-IRES that independently and directly interact with the ribosome. Importantly, these binding sites are functionally relevant to Gag translation both in vitro and ex vivo. This work provides insight into the Gag-IRES molecular mechanism and gives compelling evidence for its physiological importance. It allows us to propose original hypotheses about the IRES physiological role and conservation among primate lentiviruses. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Dissecting the genetic structure and admixture of four geographical Malay populations.

PubMed

Deng, Lian; Hoh, Boon-Peng; Lu, Dongsheng; Saw, Woei-Yuh; Twee-Hee Ong, Rick; Kasturiratne, Anuradhani; de Silva, H Janaka; Zilfalil, Bin Alwi; Kato, Norihiro; Wickremasinghe, Ananda R; Teo, Yik-Ying; Xu, Shuhua

2015-09-23

The Malay people are an important ethnic composition in Southeast Asia, but their genetic make-up and population structure remain poorly studied. Here we conducted a genome-wide study of four geographical Malay populations: Peninsular Malaysian Malay (PMM), Singaporean Malay (SGM), Indonesian Malay (IDM) and Sri Lankan Malay (SLM). All the four Malay populations showed substantial admixture with multiple ancestries. We identified four major ancestral components in Malay populations: Austronesian (17%-62%), Proto-Malay (15%-31%), East Asian (4%-16%) and South Asian (3%-34%). Approximately 34% of the genetic makeup of SLM is of South Asian ancestry, resulting in its distinct genetic pattern compared with the other three Malay populations. Besides, substantial differentiation was observed between the Malay populations from the north and the south, and between those from the west and the east. In summary, this study revealed that the genetic identity of the Malays comprises a mixed entity of multiple ancestries represented by Austronesian, Proto-Malay, East Asian and South Asian, with most of the admixture events estimated to have occurred 175 to 1,500 years ago, which in turn suggests that geographical isolation and independent admixture have significantly shaped the genetic architectures and the diversity of the Malay populations.

White light emission of monolithic InGaN/GaN grown on morphology-controlled, nanostructured GaN templates.

PubMed

Song, Keun Man; Kim, Do-Hyun; Kim, Jong-Min; Cho, Chu-Young; Choi, Jehyuk; Kim, Kahee; Park, Jinsup; Kim, Hogyoug

2017-06-02

We demonstrated an InGaN/GaN-based, monolithic, white light-emitting diode (LED) without phosphors by using morphology-controlled active layers formed on multi-facet GaN templates containing polar and semipolar surfaces. The nanostructured surface morphology was controlled by changing the growth time, and distinct multiple photoluminescence peaks were observed at 360, 460, and 560 nm; these features were caused by InGaN/GaN-based multiple quantum wells (MQWs) on the nanostructured facets. The origin of each multi-peak was related to the different indium (In) compositions in the different planes of the quantum wells grown on the nanostructured GaN. The emitting units of MQWs in the LED structures were continuously connected, which is different from other GaN-based nanorod or nanowire LEDs. Therefore, the suggested structure had a larger active area. From the electroluminescence spectrum of the fabricated LED, monolithic white light emission with CIE color coordinates of x = 0.306 and y = 0.333 was achieved via multi-facet control combined with morphology control of the metal organic chemical vapor deposition-selective area growth of InGaN/GaN MQWs.

White light emission of monolithic InGaN/GaN grown on morphology-controlled, nanostructured GaN templates

NASA Astrophysics Data System (ADS)

Song, Keun Man; Kim, Do-Hyun; Kim, Jong-Min; Cho, Chu-Young; Choi, Jehyuk; Kim, Kahee; Park, Jinsup; Kim, Hogyoug

2017-06-01

We demonstrated an InGaN/GaN-based, monolithic, white light-emitting diode (LED) without phosphors by using morphology-controlled active layers formed on multi-facet GaN templates containing polar and semipolar surfaces. The nanostructured surface morphology was controlled by changing the growth time, and distinct multiple photoluminescence peaks were observed at 360, 460, and 560 nm; these features were caused by InGaN/GaN-based multiple quantum wells (MQWs) on the nanostructured facets. The origin of each multi-peak was related to the different indium (In) compositions in the different planes of the quantum wells grown on the nanostructured GaN. The emitting units of MQWs in the LED structures were continuously connected, which is different from other GaN-based nanorod or nanowire LEDs. Therefore, the suggested structure had a larger active area. From the electroluminescence spectrum of the fabricated LED, monolithic white light emission with CIE color coordinates of x = 0.306 and y = 0.333 was achieved via multi-facet control combined with morphology control of the metal organic chemical vapor deposition-selective area growth of InGaN/GaN MQWs.

Interoperation transfer in Chinese-English bilinguals' arithmetic.

PubMed

Campbell, Jamie I D; Dowd, Roxanne R

2012-10-01

We examined interoperation transfer of practice in adult Chinese-English bilinguals' memory for simple multiplication (6 × 8 = 48) and addition (6 + 8 = 14) facts. The purpose was to determine whether they possessed distinct number-fact representations in both Chinese (L1) and English (L2). Participants repeatedly practiced multiplication problems (e.g., 4 × 5 = ?), answering a subset in L1 and another subset in L2. Then separate groups answered corresponding addition problems (4 + 5 = ?) and control addition problems in either L1 (N = 24) or L2 (N = 24). The results demonstrated language-specific negative transfer of multiplication practice to corresponding addition problems. Specifically, large simple addition problems (sum > 10) presented a significant response time cost (i.e., retrieval-induced forgetting) after their multiplication counterparts were practiced in the same language, relative to practice in the other language. The results indicate that our Chinese-English bilinguals had multiplication and addition facts represented in distinct language-specific memory stores.

Postural Communication of Emotion: Perception of Distinct Poses of Five Discrete Emotions.

PubMed

Lopez, Lukas D; Reschke, Peter J; Knothe, Jennifer M; Walle, Eric A

2017-01-01

Emotion can be communicated through multiple distinct modalities. However, an often-ignored channel of communication is posture. Recent research indicates that bodily posture plays an important role in the perception of emotion. However, research examining postural communication of emotion is limited by the variety of validated emotion poses and unknown cohesion of categorical and dimensional ratings. The present study addressed these limitations. Specifically, we examined individuals' (1) categorization of emotion postures depicting 5 discrete emotions (joy, sadness, fear, anger, and disgust), (2) categorization of different poses depicting the same discrete emotion, and (3) ratings of valence and arousal for each emotion pose. Findings revealed that participants successfully categorized each posture as the target emotion, including disgust. Moreover, participants accurately identified multiple distinct poses within each emotion category. In addition to the categorical responses, dimensional ratings of valence and arousal revealed interesting overlap and distinctions between and within emotion categories. These findings provide the first evidence of an identifiable posture for disgust and instantiate the principle of equifinality of emotional communication through the inclusion of distinct poses within emotion categories. Additionally, the dimensional ratings corroborated the categorical data and provide further granularity for future researchers to consider in examining how distinct emotion poses are perceived.

Multiple-stage structure transformation of organic-inorganic hybrid perovskite CH 3 NH 3 PbI 3

DOE PAGES

Chen, Qiong; Liu, Henan; Kim, Hui -Seon; ...

2016-09-15

In this study, by performing spatially resolved Raman and photoluminescence spectroscopy with varying excitation wavelength, density, and data acquisition parameters, we achieve a unified understanding towards the spectroscopy signatures of the organic-inorganic hybrid perovskite, transforming from the pristine state (CH 3NH 3PbI 3) to the fully degraded state (i.e., PbI 2) for samples with varying crystalline domain size from mesoscopic scale (approximately 100 nm) to macroscopic size (centimeters), synthesized by three different techniques. We show that the hybrid perovskite exhibits multiple stages of structure transformation occurring either spontaneously or under light illumination, with exceptionally high sensitivity to the illumination conditionsmore » (e.g., power, illumination time, and interruption pattern). We highlight four transformation stages (stages I-IV, with stage I being the pristine state) along either the spontaneous or photoinduced degradation path exhibiting distinctly different Raman spectroscopy features at each stage, and point out that previously reported Raman spectra in the literature reflect highly degraded structures of either stage III or stage IV. Additional characteristic optical features of partially degraded materials under the joint action of spontaneous and photodegradation are also given. This study offers reliable benchmark results for understanding the intrinsic material properties and structure transformation of this unique category of hybrid materials, and the findings are pertinently important to a wide range of potential applications where the hybrid material is expected to function in greatly different environment and light-matter interaction conditions.« less

Multiple-Stage Structure Transformation of Organic-Inorganic Hybrid Perovskite CH3NH3PbI3

NASA Astrophysics Data System (ADS)

Chen, Qiong; Liu, Henan; Kim, Hui-Seon; Liu, Yucheng; Yang, Mengjin; Yue, Naili; Ren, Gang; Zhu, Kai; Liu, Shengzhong; Park, Nam-Gyu; Zhang, Yong

2016-07-01

By performing spatially resolved Raman and photoluminescence spectroscopy with varying excitation wavelength, density, and data acquisition parameters, we achieve a unified understanding towards the spectroscopy signatures of the organic-inorganic hybrid perovskite, transforming from the pristine state (CH3NH3PbI3 ) to the fully degraded state (i.e., PbI2 ) for samples with varying crystalline domain size from mesoscopic scale (approximately 100 nm) to macroscopic size (centimeters), synthesized by three different techniques. We show that the hybrid perovskite exhibits multiple stages of structure transformation occurring either spontaneously or under light illumination, with exceptionally high sensitivity to the illumination conditions (e.g., power, illumination time, and interruption pattern). We highlight four transformation stages (stages I-IV, with stage I being the pristine state) along either the spontaneous or photoinduced degradation path exhibiting distinctly different Raman spectroscopy features at each stage, and point out that previously reported Raman spectra in the literature reflect highly degraded structures of either stage III or stage IV. Additional characteristic optical features of partially degraded materials under the joint action of spontaneous and photodegradation are also given. This study offers reliable benchmark results for understanding the intrinsic material properties and structure transformation of this unique category of hybrid materials, and the findings are pertinently important to a wide range of potential applications where the hybrid material is expected to function in greatly different environment and light-matter interaction conditions.

Using lake sediments from Buarvatnet to reconstruct multiple episodic events found at Folgefonn Peninsula, Norway

NASA Astrophysics Data System (ADS)

Roethe, T.; Bakke, J.; Støren, E.

2016-12-01

Here we present work in progress from Buarvatnet at the Folgefonn Peninsula, located on the west coast of Norway. Earlier work from Buarvatnet indicated several distinct spikes in the Silica count rates, detected by the ITRAX surface XRF-scanner. However, the process behind these distinct spikes was not understood. The arrival of high-resolution and innovative instruments at EARTHLAB, in particular the computed tomography (CT) scanner and grain Morphometer, have the potential to get a process-based understanding of these distinct layers and unravel the frequency and timing of such events. Multiple sediment cores were retrieved using a modified piston corer and a Uwitech corer from Buarvatnet. The sediments have been analysed using a multi-proxy approach and the analyses included magnetic properties, loss-on-ignition, dry bulk density, grain size/shape, geochemical analysis (XRF scanning) and CT-scanning. Accurate age-control will be achieved through 210Pb dating of the top-most sediments and 14C dating of terrestrial macrofossils. The lithostratigraphy of the 3.6 m long master sediment core from Buarvatnet is divided into three distinct units. The lower most unit ( 87 cm) is massive with fine-grained greyish sediments, most likely representing the deglaciation of the area. A 224 cm long unit is found above, characterised as dark brown gyttja with multiple thin layers (sub-mm to cm thick) of fine grained sediments. Also in this unit is two distinct sub-units showing a finer upwards sequence. At top, a gradual transition from dark brown gyttja to grey fine-grained sediments is found in the upper-most 19 cm of the sediment core. In total 16 distinct layers is found in the gyttja sequence, including the two sub-units, based on the lithostratigraphy and the prelimnary results from the magnetic, physical and geochemical properties. A preliminary hypothesis is that these distinct layers are due to outburst floods from a glacier-dammed lake upstream from Buarvatnet. In such a scenario, a bedrock threshold dams the meltwater from the retreating glacier and an outburst flood is triggered when the glacier calves or advances into the lake. Understanding the processes behind the multiple events is therefore important in order to highlight the potential hazards in rapid outburst floods in a warming world.

Microspheres Assembled from Chitosan-Graft-Poly(lactic acid) Micelle-Like Core-Shell Nanospheres for Distinctly Controlled Release of Hydrophobic and Hydrophilic Biomolecules.

PubMed

Niu, Xufeng; Liu, Zhongning; Hu, Jiang; Rambhia, Kunal J; Fan, Yubo; Ma, Peter X

2016-07-01

To simultaneously control inflammation and facilitate dentin regeneration, a copolymeric micelle-in-microsphere platform is developed in this study, aiming to simultaneously release a hydrophobic drug to suppress inflammation and a hydrophilic biomolecule to enhance odontogenic differentiation of dental pulp stem cells in a distinctly controlled fashion. A series of chitosan-graft-poly(lactic acid) copolymers is synthesized with varying lactic acid and chitosan weight ratios, self-assembled into nanoscale micelle-like core-shell structures in an aqueous system, and subsequently crosslinked into microspheres through electrostatic interaction with sodium tripolyphosphate. A hydrophobic biomolecule either coumarin-6 or fluocinolone acetonide (FA) is encapsulated into the hydrophobic cores of the micelles, while a hydrophilic biomolecule either bovine serum albumin or bone morphogenetic protein 2 (BMP-2) is entrapped in the hydrophilic shells and the interspaces among the micelles. Both hydrophobic and hydrophilic biomolecules are delivered with distinct and tunable release patterns. Delivery of FA and BMP-2 simultaneously suppresses inflammation and enhances odontogenesis, resulting in significantly enhanced mineralized tissue regeneration. This result also demonstrates the potential for this novel delivery system to deliver multiple therapeutics and to achieve synergistic effects. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Classifying distinct basal cell carcinoma subtype by means of dermatoscopy and reflectance confocal microscopy.

PubMed

Longo, Caterina; Lallas, Aimilios; Kyrgidis, Athanassios; Rabinovitz, Harold; Moscarella, Elvira; Ciardo, Silvana; Zalaudek, Iris; Oliviero, Margaret; Losi, Amanda; Gonzalez, Salvador; Guitera, Pascale; Piana, Simonetta; Argenziano, Giuseppe; Pellacani, Giovanni

2014-10-01

The current guidelines for the management of basal cell carcinoma (BCC) suggest a different therapeutic approach according to histopathologic subtype. Although dermatoscopic and confocal criteria of BCC have been investigated, no specific studies were performed to evaluate the distinct reflectance confocal microscopy (RCM) aspects of BCC subtypes. To define the specific dermatoscopic and confocal criteria for delineating different BCC subtypes. Dermatoscopic and confocal images of histopathologically confirmed BCCs were retrospectively evaluated for the presence of predefined criteria. Frequencies of dermatoscopic and confocal parameters are provided. Univariate and adjusted odds ratios were calculated. Discriminant analyses were performed to define the independent confocal criteria for distinct BCC subtypes. Eighty-eight BCCs were included. Dermatoscopically, superficial BCCs (n=44) were primarily typified by the presence of fine telangiectasia, multiple erosions, leaf-like structures, and revealed cords connected to the epidermis and epidermal streaming upon RCM. Nodular BCCs (n=22) featured the classic dermatoscopic features and well outlined large basaloid islands upon RCM. Infiltrative BCCs (n=22) featured structureless, shiny red areas, fine telangiectasia, and arborizing vessels on dermatoscopy and dark silhouettes upon RCM. The retrospective design. Dermatoscopy and confocal microscopy can reliably classify different BCC subtypes. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Increasing functional modularity with residence time in the co-distribution of native and introduced vascular plants

PubMed Central

Hui, Cang; Richardson, David M.; Pyšek, Petr; Le Roux, Johannes J.; Kučera, Tomáš; Jarošík, Vojtěch

2013-01-01

Species gain membership of regional assemblages by passing through multiple ecological and environmental filters. To capture the potential trajectory of structural changes in regional meta-communities driven by biological invasions, one can categorize species pools into assemblages of different residence times. Older assemblages, having passed through more environmental filters, should become more functionally ordered and structured. Here we calculate the level of compartmentalization (modularity) for three different-aged assemblages (neophytes, introduced after 1500 AD; archaeophytes, introduced before 1500 AD, and natives), including 2,054 species of vascular plants in 302 reserves in central Europe. Older assemblages are more compartmentalized than younger ones, with species composition, phylogenetic structure and habitat characteristics of the modules becoming increasingly distinctive. This sheds light on two mechanisms of how alien species are functionally incorporated into regional species pools: the settling-down hypothesis of diminishing stochasticity with residence time, and the niche-mosaic hypothesis of inlaid neutral modules in regional meta-communities. PMID:24045305

Intrinsic disorder mediates the diverse regulatory functions of the Cdk inhibitor p21

PubMed Central

Wang, Yuefeng; Fisher, John C.; Mathew, Rose; Ou, Li; Otieno, Steve; Sublett, Jack; Xiao, Limin; Chen, Jianhan; Roussel, Martine F.; Kriwacki, Richard W.

2011-01-01

Traditionally, well-defined three-dimensional structure was thought to be essential for protein function. However, myriad biological functions are performed by highly dynamic, intrinsically disordered proteins (IDPs). IDPs often fold upon binding their biological targets and frequently exhibit “binding diversity” by targeting multiple ligands. We sought to understand the physical basis of IDP binding diversity and herein report that the cyclin-dependent kinase (Cdk) inhibitor, p21Cip1, adaptively binds to and inhibits the various Cdk/cyclin complexes that regulate eukaryotic cell division. Based on results from NMR spectroscopy, and biochemical and cellular assays, we show that structural adaptability of a helical sub-domain within p21 termed LH enables two other sub-domains termed D1 and D2 to specifically bind conserved surface features of the cyclin and Cdk subunits, respectively, within otherwise structurally distinct Cdk/cyclin complexes. Adaptive folding upon binding is likely to mediate the diverse biological functions of the thousands of IDPs present in eukaryotes. PMID:21358637

Complexing DNA Origami Frameworks through Sequential Self-Assembly Based on Directed Docking.

PubMed

Suzuki, Yuki; Sugiyama, Hiroshi; Endo, Masayuki

2018-06-11

Ordered DNA origami arrays have the potential to compartmentalize space into distinct periodic domains that can incorporate a variety of nanoscale objects. Herein, we used the cavities of a preassembled 2D DNA origami framework to incorporate square-shaped DNA origami structures (SQ-origamis). The framework was self-assembled on a lipid bilayer membrane from cross-shaped DNA origami structures (CR-origamis) and subsequently exposed to the SQ-origamis. High-speed AFM revealed the dynamic adsorption/desorption behavior of the SQ-origamis, which resulted in continuous changing of their arrangements in the framework. These dynamic SQ-origamis were trapped in the cavities by increasing the Mg 2+ concentration or by introducing sticky-ended cohesions between extended staples, both from the SQ- and CR-origamis, which enabled the directed docking of the SQ-origamis. Our study offers a platform to create supramolecular structures or systems consisting of multiple DNA origami components. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural characterization of toxic oligomers that are kinetically trapped during α-synuclein fibril formation

PubMed Central

Chen, Serene W.; Drakulic, Srdja; Deas, Emma; Ouberai, Myriam; Aprile, Francesco A.; Arranz, Rocío; Ness, Samuel; Roodveldt, Cintia; Guilliams, Tim; De-Genst, Erwin J.; Klenerman, David; Wood, Nicholas W.; Knowles, Tuomas P.J.; Alfonso, Carlos; Rivas, Germán; Abramov, Andrey Y.; Valpuesta, José María; Dobson, Christopher M.; Cremades, Nunilo

2015-01-01

We describe the isolation and detailed structural characterization of stable toxic oligomers of α-synuclein that have accumulated during the process of amyloid formation. Our approach has allowed us to identify distinct subgroups of oligomers and to probe their molecular architectures by using cryo-electron microscopy (cryoEM) image reconstruction techniques. Although the oligomers exist in a range of sizes, with different extents and nature of β-sheet content and exposed hydrophobicity, they all possess a hollow cylindrical architecture with similarities to certain types of amyloid fibril, suggesting that the accumulation of at least some forms of amyloid oligomers is likely to be a consequence of very slow rates of rearrangement of their β-sheet structures. Our findings reveal the inherent multiplicity of the process of protein misfolding and the key role the β-sheet geometry acquired in the early stages of the self-assembly process plays in dictating the kinetic stability and the pathological nature of individual oligomeric species. PMID:25855634

Pressure evolution of electrical transport in the 3D topological insulator (Bi,Sb) 2 (Se,Te) 3

DOE PAGES

Jeffries, J. R.; Butch, N. P.; Vohra, Y. K.; ...

2015-03-18

The group V-VI compounds|like Bi 2Se 3, Sb 2Te 3, or Bi 2Te 3|have been widely studied in recent years for their bulk topological properties. The high-Z members of this series form with the same crystal structure, and are therefore amenable to isostructural substitution studies. It is possible to tune the Bi-Sb and Te-Se ratios such that the material exhibits insulating behavior, thus providing an excellent platform for understanding how a topological insulator evolves with applied pressure. We report our observations of the pressure-dependent electrical transport and crystal structure of a pseudobinary (Bi,Sb) 2(Te,Se) 3 compound. Similar to some ofmore » its sister compounds, the (Bi,Sb) 2(Te,Se) 3 pseudobinary compound undergoes multiple, pressure-induced phase transformations that result in metallization, the onset of a close-packed crystal structure, and the development of distinct superconducting phases.« less

Time-resolved observation of protein allosteric communication

PubMed Central

Buchenberg, Sebastian; Sittel, Florian; Stock, Gerhard

2017-01-01

Allostery represents a fundamental mechanism of biological regulation that is mediated via long-range communication between distant protein sites. Although little is known about the underlying dynamical process, recent time-resolved infrared spectroscopy experiments on a photoswitchable PDZ domain (PDZ2S) have indicated that the allosteric transition occurs on multiple timescales. Here, using extensive nonequilibrium molecular dynamics simulations, a time-dependent picture of the allosteric communication in PDZ2S is developed. The simulations reveal that allostery amounts to the propagation of structural and dynamical changes that are genuinely nonlinear and can occur in a nonlocal fashion. A dynamic network model is constructed that illustrates the hierarchy and exceeding structural heterogeneity of the process. In compelling agreement with experiment, three physically distinct phases of the time evolution are identified, describing elastic response (≲0.1 ns), inelastic reorganization (∼100 ns), and structural relaxation (≳1μs). Issues such as the similarity to downhill folding as well as the interpretation of allosteric pathways are discussed. PMID:28760989

The Antsy Social Network: Determinants of Nest Structure and Arrangement in Asian Weaver Ants.

PubMed

Devarajan, Kadambari

2016-01-01

Asian weaver ants (Oecophylla smaragdina) are arboreal ants that are known to form mutualistic complexes with their host trees. They are eusocial ants that build elaborate nests in the canopy in tropical areas. A colony comprises of multiple nests, usually on multiple trees, and the boundaries of the colony may be difficult to identify. However, they provide the ideal model for studying group living in invertebrates since there are a definite number of nests for a given substrate, the tree. Here, we briefly examine the structure of the nests and the processes involved in the construction and maintenance of these nests. We have described the spatial arrangement of weaver ant nests on trees in two distinct tropical clusters, a few hundred kilometres apart in India. Measurements were made for 13 trees with a total of 71 nests in the two field sites. We have considered a host of biotic and abiotic factors that may be crucial in determining the location of the nesting site by Asian weaver ants. Our results indicate that tree characteristics and architecture followed by leaf features help determine nest location in Asian weaver ants. While environmental factors may not be as influential to nest arrangement, they seem to be important determinants of nest structure. The parameters that may be considered in establishing the nests could be crucial in picking the evolutionary drivers for colonial living in social organisms.

Connecting Structure-Property and Structure-Function Relationships across the Disciplines of Chemistry and Biology: Exploring Student Perceptions.

PubMed

Kohn, Kathryn P; Underwood, Sonia M; Cooper, Melanie M

2018-06-01

While many university students take science courses in multiple disciplines, little is known about how they perceive common concepts from different disciplinary perspectives. Structure-property and structure-function relationships have long been considered important explanatory concepts in the disciplines of chemistry and biology, respectively. Fourteen university students concurrently enrolled in introductory chemistry and biology courses were interviewed to explore their perceptions regarding 1) the meaning of structure, properties, and function; 2) the presentation of these concepts in their courses; and 3) how these concepts might be related. Findings suggest that the concepts of structure and properties were interpreted similarly between chemistry and biology, but students more closely associated the discussion of structure-property relationships with their chemistry courses and structure-function with biology. Despite receiving little in the way of instructional support, nine students proposed a coherent conceptual relationship, indicating that structure determines properties, which determine function. Furthermore, students described ways in which they connected and benefited from their understanding. Though many students are prepared to make these connections, we would encourage instructors to engage in cross-disciplinary conversations to understand the shared goals and disciplinary distinctions regarding these important concepts in an effort to better support students unable to construct these connections for themselves.

Characterizing the distinct structural changes associated with self-reported knee injury among individuals with incident knee osteoarthritis: Data from the osteoarthritis initiative.

PubMed

Davis, Julie E; Harkey, Matthew S; Ward, Robert J; Mackay, James W; Lu, Bing; Price, Lori Lyn; Eaton, Charles B; Barbe, Mary F; Lo, Grace H; McAlindon, Timothy E; Driban, Jeffrey B

2018-04-01

We aimed to characterize the agreement between distinct structural changes on magnetic resonance (MR) imaging and self-reported injury in the 12 months leading to incident common or accelerated knee osteoarthritis (KOA). We conducted a descriptive study using data from baseline and the first 4 annual visits of the Osteoarthritis Initiative. Knees had no radiographic KOA at baseline (Kellgren-Lawrence [KL]<2). We classified two groups: (1) accelerated KOA: a knee developed advanced-stage KOA (KL = 3 or 4) within 48 months and (2) common KOA: a knee increased in radiographic severity (excluding those with accelerated KOA). Adults were 1:1 matched based on sex. The index visit was when a person met the accelerated or common KOA criteria. We limited our sample to people with MR images and self-reported injury data at index visit and year prior. Among 226 people, we found fair agreement between self-reported injuries and distinct structural changes (kappa = 0.24 to 0.31). Most distinct structural changes were medial meniscal pathology. No distinct structural changes (e.g., root or radial tears) appeared to differ between adults who reported or did not report an injury; except, all subchondral fractures occurred in adults who developed accelerated KOA and reported an injury. While there is fair agreement between self-reported knee injuries and distinct structural changes, there is some discordance. Self-reported injury may represent a different construct from distinct structural changes that occur after joint trauma. Clin. Anat. 31:330-334, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Amyloid structure exhibits polymorphism on multiple length scales in human brain tissue

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

Liu, Jiliang; Costantino, Isabel; Venugopalan, Nagarajan

Although aggregation of Aβ amyloid fibrils into plaques in the brain is a hallmark of Alzheimer's Disease (AD), the correlation between amyloid burden and severity of symptoms is weak. One possible reason is that amyloid fibrils are structurally polymorphic and different polymorphs may contribute differentially to disease. However, the occurrence and distribution of amyloid polymorphisms in human brain is poorly documented. Here we seek to fill this knowledge gap by using X-ray microdiffraction of histological sections of human tissue to map the abundance, orientation and structural heterogeneities of amyloid within individual plaques; among proximal plaques and in subjects with distinctmore » clinical histories. A 5 µ x-ray beam was used to generate diffraction data with each pattern arising from a scattering volume of only ~ 450 µ3 , making possible collection of dozens to hundreds of diffraction patterns from a single amyloid plaque. X-ray scattering from these samples exhibited all the properties expected for scattering from amyloid. Amyloid distribution was mapped using the intensity of its signature 4.7 Å reflection which also provided information on the orientation of amyloid fibrils across plaques. Margins of plaques exhibited a greater degree of orientation than cores and orientation around blood vessels frequently appeared tangential. Variation in the structure of Aβ fibrils is reflected in the shape of the 4.7 Å peak which usually appears as a doublet. Variations in this peak correspond to differences between the structure of amyloid within cores of plaques and at their periphery. Examination of tissue from a mismatch case - an individual with high plaque burden but no overt signs of dementia at time of death - revealed a diversity of structure and spatial distribution of amyloid that is distinct from typical AD cases. We demonstrate the existence of structural polymorphisms among amyloid within and among plaques of a single individual and suggest the existence of distinct differences in the organization of amyloid in subjects with different clinical presentations.« less

Amyloid structure exhibits polymorphism on multiple length scales in human brain tissue

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

Liu, Jiliang; Costantino, Isabel; Venugopalan, Nagarajan

Although aggregation of Aβ amyloid fibrils into plaques in the brain is a hallmark of Alzheimer's Disease (AD), the correlation between amyloid burden and severity of symptoms is weak. One possible reason is that amyloid fibrils are structurally polymorphic and different polymorphs may contribute differentially to disease. However, the occurrence and distribution of amyloid polymorphisms in human brain is poorly documented. Here we seek to fill this knowledge gap by using X-ray microdiffraction of histological sections of human tissue to map the abundance, orientation and structural heterogeneities of amyloid within individual plaques; among proximal plaques and in subjects with distinctmore » clinical histories. A 5 µ x-ray beam was used to generate diffraction data with each pattern arising from a scattering volume of only ~ 450 µ3 , making possible collection of dozens to hundreds of diffraction patterns from a single amyloid plaque. X-ray scattering from these samples exhibited all the properties expected for scattering from amyloid. Amyloid distribution was mapped using the intensity of its signature 4.7 Å reflection which also provided information on the orientation of amyloid fibrils across plaques. Margins of plaques exhibited a greater degree of orientation than cores and orientation around blood vessels frequently appeared tangential. Variation in the structure of Aβ fibrils is reflected in the shape of the 4.7 Å peak which usually appears as a doublet. Variations in this peak correspond to differences between the structure of amyloid within cores of plaques and at their periphery. Examination of tissue from a mismatch case - an individual with high plaque burden but no overt signs of dementia at time of death - revealed a diversity of structure and spatial distribution of amyloid that is distinct from typical AD cases. As a result, we demonstrate the existence of structural polymorphisms among amyloid within and among plaques of a single individual and suggest the existence of distinct differences in the organization of amyloid in subjects with different clinical presentations.« less

Amyloid structure exhibits polymorphism on multiple length scales in human brain tissue

DOE PAGES

Liu, Jiliang; Costantino, Isabel; Venugopalan, Nagarajan; ...

2016-09-15

Although aggregation of Aβ amyloid fibrils into plaques in the brain is a hallmark of Alzheimer's Disease (AD), the correlation between amyloid burden and severity of symptoms is weak. One possible reason is that amyloid fibrils are structurally polymorphic and different polymorphs may contribute differentially to disease. However, the occurrence and distribution of amyloid polymorphisms in human brain is poorly documented. Here we seek to fill this knowledge gap by using X-ray microdiffraction of histological sections of human tissue to map the abundance, orientation and structural heterogeneities of amyloid within individual plaques; among proximal plaques and in subjects with distinctmore » clinical histories. A 5 µ x-ray beam was used to generate diffraction data with each pattern arising from a scattering volume of only ~ 450 µ3 , making possible collection of dozens to hundreds of diffraction patterns from a single amyloid plaque. X-ray scattering from these samples exhibited all the properties expected for scattering from amyloid. Amyloid distribution was mapped using the intensity of its signature 4.7 Å reflection which also provided information on the orientation of amyloid fibrils across plaques. Margins of plaques exhibited a greater degree of orientation than cores and orientation around blood vessels frequently appeared tangential. Variation in the structure of Aβ fibrils is reflected in the shape of the 4.7 Å peak which usually appears as a doublet. Variations in this peak correspond to differences between the structure of amyloid within cores of plaques and at their periphery. Examination of tissue from a mismatch case - an individual with high plaque burden but no overt signs of dementia at time of death - revealed a diversity of structure and spatial distribution of amyloid that is distinct from typical AD cases. As a result, we demonstrate the existence of structural polymorphisms among amyloid within and among plaques of a single individual and suggest the existence of distinct differences in the organization of amyloid in subjects with different clinical presentations.« less

Dynamic Binding of Identity and Location Information: A Serial Model of Multiple Identity Tracking

ERIC Educational Resources Information Center

Oksama, Lauri; Hyona, Jukka

2008-01-01

Tracking of multiple moving objects is commonly assumed to be carried out by a fixed-capacity parallel mechanism. The present study proposes a serial model (MOMIT) to explain performance accuracy in the maintenance of multiple moving objects with distinct identities. A serial refresh mechanism is postulated, which makes recourse to continuous…

Multiple Frequency Parametric Sonar

DTIC Science & Technology

2015-09-28

300003 1 MULTIPLE FREQUENCY PARAMETRIC SONAR STATEMENT OF GOVERNMENT INTEREST [0001] The invention described herein may be manufactured and...a method for increasing the bandwidth of a parametric sonar system by using multiple primary frequencies rather than only two primary frequencies...2) Description of Prior Art [0004] Parametric sonar generates narrow beams at low frequencies by projecting sound at two distinct primary

Distinct functional roles of β-tubulin isotypes in microtubule arrays of Tetrahymena thermophila, a model single-celled organism.

PubMed

Pucciarelli, Sandra; Ballarini, Patrizia; Sparvoli, Daniela; Barchetta, Sabrina; Yu, Ting; Detrich, H William; Miceli, Cristina

2012-01-01

The multi-tubulin hypothesis proposes that each tubulin isotype performs a unique role, or subset of roles, in the universe of microtubule function(s). To test this hypothesis, we are investigating the functions of the recently discovered, noncanonical β-like tubulins (BLTs) of the ciliate, Tetrahymena thermophila. Tetrahymena forms 17 distinct microtubular structures whose assembly had been thought to be based on single α- and β-isotypes. However, completion of the macronuclear genome sequence of Tetrahymena demonstrated that this ciliate possessed a β-tubulin multigene family: two synonymous genes (BTU1 and BTU2) encode the canonical β-tubulin, BTU2, and six genes (BLT1-6) yield five divergent β-tubulin isotypes. In this report, we examine the structural features and functions of two of the BLTs (BLT1 and BLT4) and compare them to those of BTU2. With respect to BTU2, BLT1 and BLT4 had multiple sequence substitutions in their GTP-binding sites, in their interaction surfaces, and in their microtubule-targeting motifs, which together suggest that they have specialized functions. To assess the roles of these tubulins in vivo, we transformed Tetrahymena with expression vectors that direct the synthesis of GFP-tagged versions of the isotypes. We show that GFP-BLT1 and GFP-BLT4 were not detectable in somatic cilia and basal bodies, whereas GFP-BTU2 strongly labeled these structures. During cell division, GFP-BLT1 and GFP-BLT4, but not GFP-BTU2, were incorporated into the microtubule arrays of the macronucleus and into the mitotic apparatus of the micronucleus. GFP-BLT1 also participated in formation of the microtubules of the meiotic apparatus of the micronucleus during conjugation. Partitioning of the isotypes between nuclear and ciliary microtubules was confirmed biochemically. We conclude that Tetrahymena uses a family of distinct β-tubulin isotypes to construct subsets of functionally different microtubules, a result that provides strong support for the multi-tubulin hypothesis.

Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder

PubMed Central

Scheinost, Dustin; Holmes, Sophie E; DellaGioia, Nicole; Schleifer, Charlie; Matuskey, David; Abdallah, Chadi G; Hampson, Michelle; Krystal, John H; Anticevic, Alan; Esterlis, Irina

2018-01-01

Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20). These regions were then used as seeds for exploratory anatomical covariance and connectivity analyses. Reduction in volume in the anterior cingulate cortex (ACC) and lower structural covariance between the ACC and the cerebellum were observed in the MDD group. Additionally, individuals with MDD had significantly lower whole-brain intrinsic functional connectivity in the medial prefrontal cortex (mPFC). This mPFC region showed altered connectivity to the ventral lateral PFC (vlPFC) and local circuitry in MDD. Global connectivity in the ACC was negatively correlated with reported depressive symptomatology. The mPFC–vlPFC connectivity was positively correlated with depressive symptoms. Finally, we observed increased structure-to-function correlation in the PFC/ACC in the MDD group. Although across all analysis methods and modalities alterations in the PFC/ACC were a common finding, each modality and method detected alterations in subregions belonging to distinct large-scale brain networks. These exploratory results support the hypothesis that MDD is a systems level disorder affecting multiple brain networks located in the PFC and provide new insights into the pathophysiology of this disorder. PMID:28944772

Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder.

PubMed

Scheinost, Dustin; Holmes, Sophie E; DellaGioia, Nicole; Schleifer, Charlie; Matuskey, David; Abdallah, Chadi G; Hampson, Michelle; Krystal, John H; Anticevic, Alan; Esterlis, Irina

2018-04-01

Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20). These regions were then used as seeds for exploratory anatomical covariance and connectivity analyses. Reduction in volume in the anterior cingulate cortex (ACC) and lower structural covariance between the ACC and the cerebellum were observed in the MDD group. Additionally, individuals with MDD had significantly lower whole-brain intrinsic functional connectivity in the medial prefrontal cortex (mPFC). This mPFC region showed altered connectivity to the ventral lateral PFC (vlPFC) and local circuitry in MDD. Global connectivity in the ACC was negatively correlated with reported depressive symptomatology. The mPFC-vlPFC connectivity was positively correlated with depressive symptoms. Finally, we observed increased structure-to-function correlation in the PFC/ACC in the MDD group. Although across all analysis methods and modalities alterations in the PFC/ACC were a common finding, each modality and method detected alterations in subregions belonging to distinct large-scale brain networks. These exploratory results support the hypothesis that MDD is a systems level disorder affecting multiple brain networks located in the PFC and provide new insights into the pathophysiology of this disorder.

Robust Production, Crystallization, Structure Determination, and Analysis of [Fe-S] Proteins: Uncovering Control of Electron Shuttling and Gating in the Respiratory Metabolism of Molybdopterin Guanine Dinucleotide Enzymes.

PubMed

Tsai, Chi-Lin; Tainer, John A

2018-01-01

[Fe-S] clusters are essential cofactors in all domains of life. They play many biological roles due to their unique abilities for electron transfer and conformational control. Yet, producing and analyzing Fe-S proteins can be difficult and even misleading if not done anaerobically. Due to unique redox properties of [Fe-S] clusters and their oxygen sensitivity, they pose multiple challenges and can lose enzymatic activity or cause their component proteins to be structurally disordered due to [Fe-S] cluster oxidation and loss in air. Here we highlight tested protocols and strategies enabling efficient and stable [Fe-S] protein production, purification, crystallization, X-ray diffraction data collection, and structure determination. From multiple high-resolution anaerobic crystal structures, we furthermore analyze exemplary data defining [Fe-S] clusters, substrate entry, and product exit for the functional oxidation states of type II molybdo-bis(molybdopterin guanine dinucleotide) (Mo-bisMGD) enzymes. Notably, these enzymes perform electron shuttling between quinone pools and specific substrates to catalyze respiratory metabolism. The identified structure-activity relationships for this enzyme class have broad implications germane to perchlorate environments on Earth and Mars extending to an alternative mechanism underlying metabolic origins for the evolution of the oxygen atmosphere. Integrated structural analyses of type II Mo-bisMGD enzymes unveil novel distinctive shared molecular mechanisms for dynamic control of substrate entry and product release gated by hydrophobic residues. Collective findings support a prototypic model for type II Mo-bisMGD enzymes including insights for a fundamental molecular mechanistic understanding of selectivity and regulation by a conformationally gated channel with general implications for [Fe-S] cluster respiratory enzymes. © 2018 Elsevier Inc. All rights reserved.

Multiscale structure and damage tolerance of coconut shells.

PubMed

Gludovatz, B; Walsh, F; Zimmermann, E A; Naleway, S E; Ritchie, R O; Kruzic, J J

2017-12-01

We investigated the endocarp of the fruit of Cocos nucifera (i.e., the inner coconut shell), examining the structure across multiple length scales through advanced characterization techniques and in situ testing of mechanical properties. Like many biological materials, the coconut shell possesses a hierarchical structure with distinct features at different length scales that depend on orientation and age. Aged coconut was found to have a significantly stronger (ultimate tensile strength, UTS = 48.5MPa), stiffer (Young's modulus, E = 1.92GPa), and tougher (fracture resistance (R-curve) peak of K J = 3.2MPa m 1/2 ) endocarp than the younger fruit for loading in the latitudinal orientation. While the mechanical properties of coconut shell were observed to improve with age, they also become more anisotropic: the young coconut shell had the same strength (17MPa) and modulus (0.64GPa) values and similar R-curves for both longitudinal and latitudinal loading configurations, whereas the old coconut had 82% higher strength for loading in the latitudinal orientation, and >50% higher crack growth toughness for cracking on the latitudinal plane. Structural aspects affecting the mechanical properties across multiple length scales with aging were identified as improved load transfer to the cellulose crystalline nanostructure (identified by synchrotron x-ray diffraction) and sclerification of the endocarp, the latter of which included closing of the cell lumens and lignification of the cell walls. The structural changes gave a denser and mechanically superior micro and nanostructure to the old coconut shell. Additionally, the development of anisotropy was attributed to the formation of an anisotropic open channel structure throughout the shell of the old coconut that affected both crack initiation during uniaxial tensile tests and the toughening mechanisms of crack trapping and deflection during crack propagation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Polycythaemia: an unusual presentation of multiple myeloma.

PubMed

Hutchison, Elaine J; Taverna, Josephine A; Yu, Qi; Yeager, Andrew M

2016-09-20

In contrast to anaemia, polycythaemia is a distinctly uncommon finding in patients with multiple myeloma. We describe the presence of otherwise unexplained polycythaemia in a 57-year-old Caucasian man who was found to have IgG κ multiple myeloma. After treatment of myeloma, the polycythaemia resolved. We reviewed previous reports of polycythaemia associated with multiple myeloma and discuss potential pathophysiological mechanisms that link these 2 conditions. 2016 BMJ Publishing Group Ltd.

Study on the structural, optical, and electrical properties of the yellow light-emitting diode grown on free-standing (0001) GaN substrate

NASA Astrophysics Data System (ADS)

Deng, Gaoqiang; Zhang, Yuantao; Yu, Ye; Yan, Long; Li, Pengchong; Han, Xu; Chen, Liang; Zhao, Degang; Du, Guotong

2018-04-01

In this paper, GaN-based yellow light-emitting diodes (LEDs) were homoepitaxially grown on free-standing (0001) GaN substrates by metal-organic chemical vapor deposition. X-ray diffraction (XRD), photoluminescence (PL), and electroluminescence (EL) measurements were conducted to investigate the structural, optical, and electrical properties of the yellow LED. The XRD measurement results showed that the InGaN/GaN multiple quantum wells (MQWs) in the LED structure have good periodicity because the distinct MQWs related higher order satellite peaks can be clearly observed from the profile of 2θ-ω XRD scan. The low temperature (10 K) and room temperature PL measurement results yield an internal quantum efficiency of 16% for the yellow LED. The EL spectra of the yellow LED present well Gaussian distribution with relatively low linewidth (47-55 nm), indicating the homogeneous In-content in the InGaN quantum well layers in the yellow LED structure. It is believed that this work will aid in the future development of GaN on GaN LEDs with long emission wavelength.

Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome

PubMed Central

McGinty, Robert K.; Henrici, Ryan C.; Tan, Song

2014-01-01

The Polycomb group of epigenetic enzymes represses expression of developmentally regulated genes in higher eukaryotes. This group includes the Polycomb repressive complex 1 (PRC1), which ubiquitylates nucleosomal histone H2A Lys119 using its E3 ubiquitin ligase subunits, Ring1B and Bmi1, together with an E2 ubiquitin-conjugating enzyme, UbcH5c. However, the molecular mechanism of nucleosome substrate recognition by PRC1 or other chromatin enzymes is unclear. Here we present the crystal structure of the Ring1B/Bmi1/UbcH5c E3-E2 complex (the PRC1 ubiquitylation module) bound to its nucleosome core particle substrate. The structure shows how a chromatin enzyme achieves substrate specificity by interacting with multiple nucleosome surfaces spatially distinct from the site of catalysis. Our structure further reveals an unexpected role for the ubiquitin E2 enzyme in substrate recognition, and provides insight into how the related histone H2A E3 ligase, BRCA1, interacts with and ubiquitylates the nucleosome. PMID:25355358

Alternative approximation concepts for space frame synthesis

NASA Technical Reports Server (NTRS)

Lust, R. V.; Schmit, L. A.

1985-01-01

A structural synthesis methodology for the minimum mass design of 3-dimensionall frame-truss structures under multiple static loading conditions and subject to limits on displacements, rotations, stresses, local buckling, and element cross-sectional dimensions is presented. A variety of approximation concept options are employed to yield near optimum designs after no more than 10 structural analyses. Available options include: (A) formulation of the nonlinear mathematcal programming problem in either reciprocal section property (RSP) or cross-sectional dimension (CSD) space; (B) two alternative approximate problem structures in each design space; and (C) three distinct assumptions about element end-force variations. Fixed element, design element linking, and temporary constraint deletion features are also included. The solution of each approximate problem, in either its primal or dual form, is obtained using CONMIN, a feasible directions program. The frame-truss synthesis methodology is implemented in the COMPASS computer program and is used to solve a variety of problems. These problems were chosen so that, in addition to exercising the various approximation concepts options, the results could be compared with previously published work.

The impact of natural transformation on adaptation in spatially structured bacterial populations.

PubMed

Moradigaravand, Danesh; Engelstädter, Jan

2014-06-20

Recent studies have demonstrated that natural transformation and the formation of highly structured populations in bacteria are interconnected. In spite of growing evidence about this connection, little is known about the dynamics of natural transformation in spatially structured bacterial populations. In this work, we model the interdependency between the dynamics of the bacterial gene pool and those of environmental DNA in space to dissect the effect of transformation on adaptation. Our model reveals that even with only a single locus under consideration, transformation with a free DNA fragment pool results in complex adaptation dynamics that do not emerge in previous models focusing only on the gene shuffling effect of transformation at multiple loci. We demonstrate how spatial restriction on population growth and DNA diffusion in the environment affect the impact of transformation on adaptation. We found that in structured bacterial populations intermediate DNA diffusion rates predominantly cause transformation to impede adaptation by spreading deleterious alleles in the population. Overall, our model highlights distinctive evolutionary consequences of bacterial transformation in spatially restricted compared to planktonic bacterial populations.

Computational design of RNAs with complex energy landscapes.

PubMed

Höner zu Siederdissen, Christian; Hammer, Stefan; Abfalter, Ingrid; Hofacker, Ivo L; Flamm, Christoph; Stadler, Peter F

2013-12-01

RNA has become an integral building material in synthetic biology. Dominated by their secondary structures, which can be computed efficiently, RNA molecules are amenable not only to in vitro and in vivo selection, but also to rational, computation-based design. While the inverse folding problem of constructing an RNA sequence with a prescribed ground-state structure has received considerable attention for nearly two decades, there have been few efforts to design RNAs that can switch between distinct prescribed conformations. We introduce a user-friendly tool for designing RNA sequences that fold into multiple target structures. The underlying algorithm makes use of a combination of graph coloring and heuristic local optimization to find sequences whose energy landscapes are dominated by the prescribed conformations. A flexible interface allows the specification of a wide range of design goals. We demonstrate that bi- and tri-stable "switches" can be designed easily with moderate computational effort for the vast majority of compatible combinations of desired target structures. RNAdesign is freely available under the GPL-v3 license. Copyright © 2013 Wiley Periodicals, Inc.

Chromatin insulator bodies are nuclear structures that form in response to osmotic stress and cell death

PubMed Central

Schoborg, Todd; Rickels, Ryan; Barrios, Josh

2013-01-01

Chromatin insulators assist in the formation of higher-order chromatin structures by mediating long-range contacts between distant genomic sites. It has been suggested that insulators accomplish this task by forming dense nuclear foci termed insulator bodies that result from the coalescence of multiple protein-bound insulators. However, these structures remain poorly understood, particularly the mechanisms triggering body formation and their role in nuclear function. In this paper, we show that insulator proteins undergo a dramatic and dynamic spatial reorganization into insulator bodies during osmostress and cell death in a high osmolarity glycerol–p38 mitogen-activated protein kinase–independent manner, leading to a large reduction in DNA-bound insulator proteins that rapidly repopulate chromatin as the bodies disassemble upon return to isotonicity. These bodies occupy distinct nuclear territories and contain a defined structural arrangement of insulator proteins. Our findings suggest insulator bodies are novel nuclear stress foci that can be used as a proxy to monitor the chromatin-bound state of insulator proteins and provide new insights into the effects of osmostress on nuclear and genome organization. PMID:23878275

Analysis of multiple tank car releases in train accidents.

PubMed

Liu, Xiang; Liu, Chang; Hong, Yili

2017-10-01

There are annually over two million carloads of hazardous materials transported by rail in the United States. The American railroads use large blocks of tank cars to transport petroleum crude oil and other flammable liquids from production to consumption sites. Being different from roadway transport of hazardous materials, a train accident can potentially result in the derailment and release of multiple tank cars, which may result in significant consequences. The prior literature predominantly assumes that the occurrence of multiple tank car releases in a train accident is a series of independent Bernoulli processes, and thus uses the binomial distribution to estimate the total number of tank car releases given the number of tank cars derailing or damaged. This paper shows that the traditional binomial model can incorrectly estimate multiple tank car release probability by magnitudes in certain circumstances, thereby significantly affecting railroad safety and risk analysis. To bridge this knowledge gap, this paper proposes a novel, alternative Correlated Binomial (CB) model that accounts for the possible correlations of multiple tank car releases in the same train. We test three distinct correlation structures in the CB model, and find that they all outperform the conventional binomial model based on empirical tank car accident data. The analysis shows that considering tank car release correlations would result in a significantly improved fit of the empirical data than otherwise. Consequently, it is prudent to consider alternative modeling techniques when analyzing the probability of multiple tank car releases in railroad accidents. Copyright © 2017 Elsevier Ltd. All rights reserved.

Carboxyl-terminal Domain of Transient Receptor Potential Vanilloid 1 Contains Distinct Segments Differentially Involved in Capsaicin- and Heat-induced Desensitization*

PubMed Central

Joseph, John; Wang, Sen; Lee, Jongseok; Ro, Jin Y.; Chung, Man-Kyo

2013-01-01

Multiple Ca2+-dependent processes are involved in capsaicin-induced desensitization of transient receptor potential vanilloid 1 (TRPV1), but desensitization of TRPV1 by heat occurs even in the absence of extracellular Ca2+, although the mechanisms are unknown. In this study, we tested the hypothesis that capsaicin and heat desensitize TRPV1 through distinct mechanisms involving distinct structural segments of TRPV1. In HEK293 cells that heterologously express TRPV1, we found that heat-induced desensitization was not affected by the inclusion of intracellular ATP or alanine mutation of Lys155, both of which attenuate capsaicin-induced desensitization, suggesting that heat-induced desensitization occurs through mechanisms distinct from capsaicin-induced desensitization. To determine protein domains involved in heat-induced desensitization, we generated chimeric proteins between TRPV1 and TRPV3, a heat-gated channel lacking heat-induced desensitization. We found that TRPV1 with the carboxyl-terminal domain (CTD) of TRPV3 retained heat activation but was impaired in heat-induced desensitization. Further experiments using chimeric or deletion mutants within TRPV1 CTD indicated that the distal half of CTD regulates the activation and desensitization of TRPV1 in modality-specific manners. Within the distal CTD, we identified two segments that distinctly regulated capsaicin- and heat-induced desensitization. The results suggest that the activation and desensitization of TRPV1 by capsaicin and heat can be modulated differentially and disproportionally through different regions of TRPV1 CTD. Identifying the domains involved in thermal regulation of TRPV1 may facilitate the development of novel anti-hyperalgesic approaches aimed at attenuating activation and enhancing desensitization of TRPV1 by thermal stimuli. PMID:24174527

Rhodopsin TM6 Can Interact with Two Separate and Distinct Sites on Arrestin: Evidence for Structural Plasticity and Multiple Docking Modes in Arrestin–Rhodopsin Binding

PubMed Central

2015-01-01

Various studies have implicated the concave surface of arrestin in the binding of the cytosolic surface of rhodopsin. However, specific sites of contact between the two proteins have not previously been defined in detail. Here, we report that arrestin shares part of the same binding site on rhodopsin as does the transducin Gα subunit C-terminal tail, suggesting binding of both proteins to rhodopsin may share some similar underlying mechanisms. We also identify two areas of contact between the proteins near this region. Both sites lie in the arrestin N-domain, one in the so-called “finger” loop (residues 67–79) and the other in the 160 loop (residues 155–165). We mapped these sites using a novel tryptophan-induced quenching method, in which we introduced Trp residues into arrestin and measured their ability to quench the fluorescence of bimane probes attached to cysteine residues on TM6 of rhodopsin (T242C and T243C). The involvement of finger loop binding to rhodopsin was expected, but the evidence of the arrestin 160 loop contacting rhodopsin was not. Remarkably, our data indicate one site on rhodopsin can interact with multiple structurally separate sites on arrestin that are almost 30 Å apart. Although this observation at first seems paradoxical, in fact, it provides strong support for recent hypotheses that structural plasticity and conformational changes are involved in the arrestin–rhodopsin binding interface and that the two proteins may be able to interact through multiple docking modes, with arrestin binding to both monomeric and dimeric rhodopsin. PMID:24724832

Emergence of Functional Hierarchy in a Multiple Timescale Neural Network Model: A Humanoid Robot Experiment

PubMed Central

Yamashita, Yuichi; Tani, Jun

2008-01-01

It is generally thought that skilled behavior in human beings results from a functional hierarchy of the motor control system, within which reusable motor primitives are flexibly integrated into various sensori-motor sequence patterns. The underlying neural mechanisms governing the way in which continuous sensori-motor flows are segmented into primitives and the way in which series of primitives are integrated into various behavior sequences have, however, not yet been clarified. In earlier studies, this functional hierarchy has been realized through the use of explicit hierarchical structure, with local modules representing motor primitives in the lower level and a higher module representing sequences of primitives switched via additional mechanisms such as gate-selecting. When sequences contain similarities and overlap, however, a conflict arises in such earlier models between generalization and segmentation, induced by this separated modular structure. To address this issue, we propose a different type of neural network model. The current model neither makes use of separate local modules to represent primitives nor introduces explicit hierarchical structure. Rather than forcing architectural hierarchy onto the system, functional hierarchy emerges through a form of self-organization that is based on two distinct types of neurons, each with different time properties (“multiple timescales”). Through the introduction of multiple timescales, continuous sequences of behavior are segmented into reusable primitives, and the primitives, in turn, are flexibly integrated into novel sequences. In experiments, the proposed network model, coordinating the physical body of a humanoid robot through high-dimensional sensori-motor control, also successfully situated itself within a physical environment. Our results suggest that it is not only the spatial connections between neurons but also the timescales of neural activity that act as important mechanisms leading to functional hierarchy in neural systems. PMID:18989398

Structural mechanisms of chaperone mediated protein disaggregation

PubMed Central

Sousa, Rui

2014-01-01

The ClpB/Hsp104 and Hsp70 classes of molecular chaperones use ATP hydrolysis to dissociate protein aggregates and complexes, and to move proteins through membranes. ClpB/Hsp104 are members of the AAA+ family of proteins which form ring-shaped hexamers. Loops lining the pore in the ring engage substrate proteins as extended polypeptides. Interdomain rotations and conformational changes in these loops coupled to ATP hydrolysis unfold and pull proteins through the pore. This provides a mechanism that progressively disrupts local secondary and tertiary structure in substrates, allowing these chaperones to dissociate stable aggregates such as β-sheet rich prions or coiled coil SNARE complexes. While the ClpB/Hsp104 mechanism appears to embody a true power-stroke in which an ATP powered conformational change in one protein is directly coupled to movement or structural change in another, the mechanism of force generation by Hsp70s is distinct and less well understood. Both active power-stroke and purely passive mechanisms in which Hsp70 captures spontaneous fluctuations in a substrate have been proposed, while a third proposed mechanism—entropic pulling—may be able to generate forces larger than seen in ATP-driven molecular motors without the conformational coupling required for a power-stroke. The disaggregase activity of these chaperones is required for thermotolerance, but unrestrained protein complex/aggregate dissociation is potentially detrimental. Disaggregating chaperones are strongly auto-repressed, and are regulated by co-chaperones which recruit them to protein substrates and activate the disaggregases via mechanisms involving either sequential transfer of substrate from one chaperone to another and/or simultaneous interaction of substrate with multiple chaperones. By effectively subjecting substrates to multiple levels of selection by multiple chaperones, this may insure that these potent disaggregases are only activated in the appropriate context. PMID:25988153

Rhodopsin TM6 can interact with two separate and distinct sites on arrestin: evidence for structural plasticity and multiple docking modes in arrestin-rhodopsin binding.

PubMed

Sinha, Abhinav; Jones Brunette, Amber M; Fay, Jonathan F; Schafer, Christopher T; Farrens, David L

2014-05-27

Various studies have implicated the concave surface of arrestin in the binding of the cytosolic surface of rhodopsin. However, specific sites of contact between the two proteins have not previously been defined in detail. Here, we report that arrestin shares part of the same binding site on rhodopsin as does the transducin Gα subunit C-terminal tail, suggesting binding of both proteins to rhodopsin may share some similar underlying mechanisms. We also identify two areas of contact between the proteins near this region. Both sites lie in the arrestin N-domain, one in the so-called "finger" loop (residues 67-79) and the other in the 160 loop (residues 155-165). We mapped these sites using a novel tryptophan-induced quenching method, in which we introduced Trp residues into arrestin and measured their ability to quench the fluorescence of bimane probes attached to cysteine residues on TM6 of rhodopsin (T242C and T243C). The involvement of finger loop binding to rhodopsin was expected, but the evidence of the arrestin 160 loop contacting rhodopsin was not. Remarkably, our data indicate one site on rhodopsin can interact with multiple structurally separate sites on arrestin that are almost 30 Å apart. Although this observation at first seems paradoxical, in fact, it provides strong support for recent hypotheses that structural plasticity and conformational changes are involved in the arrestin-rhodopsin binding interface and that the two proteins may be able to interact through multiple docking modes, with arrestin binding to both monomeric and dimeric rhodopsin.

Catalyst-controlled oligomerization for the collective synthesis of polypyrroloindoline natural products.

PubMed

Jamison, Christopher R; Badillo, Joseph J; Lipshultz, Jeffrey M; Comito, Robert J; MacMillan, David W C

2017-12-01

In nature, many organisms generate large families of natural product metabolites that have related molecular structures as a means to increase functional diversity and gain an evolutionary advantage against competing systems within the same environment. One pathway commonly employed by living systems to generate these large classes of structurally related families is oligomerization, wherein a series of enzymatically catalysed reactions is employed to generate secondary metabolites by iteratively appending monomers to a growing serial oligomer chain. The polypyrroloindolines are an interesting class of oligomeric natural products that consist of multiple cyclotryptamine subunits. Herein we describe an iterative application of asymmetric copper catalysis towards the synthesis of six distinct oligomeric polypyrroloindoline natural products: hodgkinsine, hodgkinsine B, idiospermuline, quadrigemine H and isopsychotridine B and C. Given the customizable nature of the small-molecule catalysts employed, we demonstrate that this strategy is further amenable to the construction of quadrigemine H-type alkaloids not isolated previously from natural sources.

Polymorphic design of DNA origami structures through mechanical control of modular components.

PubMed

Lee, Chanseok; Lee, Jae Young; Kim, Do-Nyun

2017-12-12

Scaffolded DNA origami enables the bottom-up fabrication of diverse DNA nanostructures by designing hundreds of staple strands, comprised of complementary sequences to the specific binding locations of a scaffold strand. Despite its exceptionally high design flexibility, poor reusability of staples has been one of the major hurdles to fabricate assorted DNA constructs in an effective way. Here we provide a rational module-based design approach to create distinct bent shapes with controllable geometries and flexibilities from a single, reference set of staples. By revising the staple connectivity within the desired module, we can control the location, stiffness, and included angle of hinges precisely, enabling the construction of dozens of single- or multiple-hinge structures with the replacement of staple strands up to 12.8% only. Our design approach, combined with computational shape prediction and analysis, can provide a versatile and cost-effective procedure in the design of DNA origami shapes with stiffness-tunable units.

Neutral axis determination of full size concrete structures using coda wave measurements

NASA Astrophysics Data System (ADS)

Jiang, Hanwan; Zhan, Hanyu; Zhuang, Chenxu; Jiang, Ruinian

2018-03-01

Coda waves experiencing multiple scattering behaviors are sensitive to weak changes occurring in media. In this paper, a typical four-point bending test with varied external loads is conducted on a 30-meter T-beam that is removed from a bridge after being in service for 15 years, and the coda wave signals are collected with a couple of sources-receivers pairs. Then the observed coda waves at different loads are compared to calculate their relative velocity variations, which are utilized as the parameter to distinct the compression and tensile zones as well as determine the neutral axis position. Without any prior knowledge of the concrete beam, the estimated axis position agrees well with the associated strain gage measurement results, and the zones bearing stress and tension behaviors are indicated. The presented work offers significant potential for Non-Destructive Testing and Evaluation of full-size concrete structures in future work.

Catalyst-controlled oligomerization for the collective synthesis of polypyrroloindoline natural products

NASA Astrophysics Data System (ADS)

Jamison, Christopher R.; Badillo, Joseph J.; Lipshultz, Jeffrey M.; Comito, Robert J.; MacMillan, David W. C.

2017-12-01

In nature, many organisms generate large families of natural product metabolites that have related molecular structures as a means to increase functional diversity and gain an evolutionary advantage against competing systems within the same environment. One pathway commonly employed by living systems to generate these large classes of structurally related families is oligomerization, wherein a series of enzymatically catalysed reactions is employed to generate secondary metabolites by iteratively appending monomers to a growing serial oligomer chain. The polypyrroloindolines are an interesting class of oligomeric natural products that consist of multiple cyclotryptamine subunits. Herein we describe an iterative application of asymmetric copper catalysis towards the synthesis of six distinct oligomeric polypyrroloindoline natural products: hodgkinsine, hodgkinsine B, idiospermuline, quadrigemine H and isopsychotridine B and C. Given the customizable nature of the small-molecule catalysts employed, we demonstrate that this strategy is further amenable to the construction of quadrigemine H-type alkaloids not isolated previously from natural sources.

Direct observation of fast protein conformational switching.

PubMed

Ishikawa, Haruto; Kwak, Kyungwon; Chung, Jean K; Kim, Seongheun; Fayer, Michael D

2008-06-24

Folded proteins can exist in multiple conformational substates. Each substate reflects a local minimum on the free-energy landscape with a distinct structure. By using ultrafast 2D-IR vibrational echo chemical-exchange spectroscopy, conformational switching between two well defined substates of a myoglobin mutant is observed on the approximately 50-ps time scale. The conformational dynamics are directly measured through the growth of cross peaks in the 2D-IR spectra of CO bound to the heme active site. The conformational switching involves motion of the distal histidine/E helix that changes the location of the imidazole side group of the histidine. The exchange between substates changes the frequency of the CO, which is detected by the time dependence of the 2D-IR vibrational echo spectrum. These results demonstrate that interconversion between protein conformational substates can occur on very fast time scales. The implications for larger structural changes that occur on much longer time scales are discussed.

A comprehensive strategy for designing a Web-based medical curriculum.

PubMed Central

Zucker, J.; Chase, H.; Molholt, P.; Bean, C.; Kahn, R. M.

1996-01-01

In preparing for a full featured online curriculum, it is necessary to develop scaleable strategies for software design that will support the pedagogical goals of the curriculum and which will address the issues of acquisition and updating of materials, of robust content-based linking, and of integration of the online materials into other methods of learning. A complete online curriculum, as distinct from an individual computerized module, must provide dynamic updating of both content and structure and an easy pathway from the professor's notes to the finished online product. At the College of Physicians and Surgeons, we are developing such strategies including a scripted text conversion process that uses the Hypertext Markup Language (HTML) as structural markup rather than as display markup, automated linking by the use of relational databases and the Unified Medical Language System (UMLS), integration of text, images, and multimedia along with interface designs which promote multiple contexts and collaborative study. PMID:8947624

Interactions of a Pop5/Rpp1 heterodimer with the catalytic domain of RNase MRP.

PubMed

Perederina, Anna; Khanova, Elena; Quan, Chao; Berezin, Igor; Esakova, Olga; Krasilnikov, Andrey S

2011-10-01

Ribonuclease (RNase) MRP is a multicomponent ribonucleoprotein complex closely related to RNase P. RNase MRP and eukaryotic RNase P share most of their protein components, as well as multiple features of their catalytic RNA moieties, but have distinct substrate specificities. While RNase P is practically universally found in all three domains of life, RNase MRP is essential in eukaryotes. The structural organizations of eukaryotic RNase P and RNase MRP are poorly understood. Here, we show that Pop5 and Rpp1, protein components found in both RNase P and RNase MRP, form a heterodimer that binds directly to the conserved area of the putative catalytic domain of RNase MRP RNA. The Pop5/Rpp1 binding site corresponds to the protein binding site in bacterial RNase P RNA. Structural and evolutionary roles of the Pop5/Rpp1 heterodimer in RNases P and MRP are discussed.

Interactions of a Pop5/Rpp1 heterodimer with the catalytic domain of RNase MRP

PubMed Central

Perederina, Anna; Khanova, Elena; Quan, Chao; Berezin, Igor; Esakova, Olga; Krasilnikov, Andrey S.

2011-01-01

Ribonuclease (RNase) MRP is a multicomponent ribonucleoprotein complex closely related to RNase P. RNase MRP and eukaryotic RNase P share most of their protein components, as well as multiple features of their catalytic RNA moieties, but have distinct substrate specificities. While RNase P is practically universally found in all three domains of life, RNase MRP is essential in eukaryotes. The structural organizations of eukaryotic RNase P and RNase MRP are poorly understood. Here, we show that Pop5 and Rpp1, protein components found in both RNase P and RNase MRP, form a heterodimer that binds directly to the conserved area of the putative catalytic domain of RNase MRP RNA. The Pop5/Rpp1 binding site corresponds to the protein binding site in bacterial RNase P RNA. Structural and evolutionary roles of the Pop5/Rpp1 heterodimer in RNases P and MRP are discussed. PMID:21878546

Streaks, multiplets, and holes: High-resolution spatio-temporal behavior of Parkfield seismicity

USGS Publications Warehouse

Waldhauser, F.; Ellsworth, W.L.; Schaff, D.P.; Cole, A.

2004-01-01

Double-difference locations of ???8000 earthquakes from 1969-2002 on the Parkfield section of the San Andreas Fault reveal detailed fault structures and seismicity that is, although complex, highly organized in both space and time. Distinctive features of the seismicity include: 1) multiple recurrence of earthquakes of the same size at precisely the same location on the fault (multiplets), implying frictional or geometric controls on their location and size; 2) sub-horizontal alignments of hypocenters along the fault plane (streaks), suggestive of rheological transitions within the fault zone and/or stress concentrations between locked and creeping areas; 3) regions devoid of microearthquakes with typical dimensions of 1-5 km (holes), one of which contains the M6 1966 Parkfield earthquake hypocenter. These features represent long lived structures that persist through many cycles of individual event. Copyright 2004 by the American Geophysical Union.

Structural evolution of glycan recognition by a family of potent HIV antibodies.

PubMed

Garces, Fernando; Sok, Devin; Kong, Leopold; McBride, Ryan; Kim, Helen J; Saye-Francisco, Karen F; Julien, Jean-Philippe; Hua, Yuanzi; Cupo, Albert; Moore, John P; Paulson, James C; Ward, Andrew B; Burton, Dennis R; Wilson, Ian A

2014-09-25

The HIV envelope glycoprotein (Env) is densely covered with self-glycans that should help shield it from recognition by the human immune system. Here, we examine how a particularly potent family of broadly neutralizing antibodies (Abs) has evolved common and distinct structural features to counter the glycan shield and interact with both glycan and protein components of HIV Env. The inferred germline antibody already harbors potential binding pockets for a glycan and a short protein segment. Affinity maturation then leads to divergent evolutionary branches that either focus on a single glycan and protein segment (e.g., Ab PGT124) or engage multiple glycans (e.g., Abs PGT121-123). Furthermore, other surrounding glycans are avoided by selecting an appropriate initial antibody shape that prevents steric hindrance. Such molecular recognition lessons are important for engineering proteins that can recognize or accommodate glycans. Copyright © 2014 Elsevier Inc. All rights reserved.

Femtosecond laser induced tunable surface transformations on (111) Si aided by square grids diffraction

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

Han, Weina; Jiang, Lan; Li, Xiaowei, E-mail: lixiaowei@bit.edu.cn

We report an extra freedom to modulate the femtosecond laser energy distribution to control the surface ablated structures through a copper-grid mask. Due to the reduced deposited pulse energy by changing the scanning speed or the pulse fluence, a sequential evolution of three distinctly different surface patterns with periodic distributions is formed, namely, striped ripple lines, ripple microdots, and surface modification. By changing the scanning speed, the number of the multiple dots in a lattice can be modulated. Moreover, by exploring the ablation process through the copper grid mask, it shows an abnormal enhanced ablation effect with strong dependence ofmore » the diffraction-aided fs laser ablated surface structures on polarization direction. The sensitivity shows a quasi-cosinusoid-function with a periodicity of π/2. Particularly, the connection process of striped ripple lines manifests a preferential formation direction with the laser polarization.« less

The development of comparative bias index

NASA Astrophysics Data System (ADS)

Aimran, Ahmad Nazim; Ahmad, Sabri; Afthanorhan, Asyraf; Awang, Zainudin

2017-08-01

Structural Equation Modeling (SEM) is a second generation statistical analysis techniques developed for analyzing the inter-relationships among multiple variables in a model simultaneously. There are two most common used methods in SEM namely Covariance-Based Structural Equation Modeling (CB-SEM) and Partial Least Square Path Modeling (PLS-PM). There have been continuous debates among researchers in the use of PLS-PM over CB-SEM. While there is few studies were conducted to test the performance of CB-SEM and PLS-PM bias in estimating simulation data. This study intends to patch this problem by a) developing the Comparative Bias Index and b) testing the performance of CB-SEM and PLS-PM using developed index. Based on balanced experimental design, two multivariate normal simulation data with of distinct specifications of size 50, 100, 200 and 500 are generated and analyzed using CB-SEM and PLS-PM.

Application of the Ugi reaction with multiple amino acid-derived components: synthesis and conformational evaluation of piperazine-based minimalist peptidomimetics.

PubMed

Stucchi, Mattia; Cairati, Silvia; Cetin-Atalay, Rengul; Christodoulou, Michael S; Grazioso, Giovanni; Pescitelli, Gennaro; Silvani, Alessandra; Yildirim, Deniz Cansen; Lesma, Giordano

2015-05-07

The concurrent employment of α-amino acid-derived chiral components such as aldehydes and α-isocyanoacetates, in a sequential Ugi reaction/cyclization two-step strategy, opens the door to the synthesis of three structurally distinct piperazine-based scaffolds, characterized by the presence of L-Ala and/or L-Phe-derived side chains and bearing appropriate functionalities to be easily applied in peptide chemistry. By means of computational studies, these scaffolds have been demonstrated to act as minimalist peptidomimetics, able to mimic a well defined range of peptide secondary structures and therefore potentially useful for the synthesis of small-molecule PPI modulators. Preliminary biological evaluation of two different resistant hepatocellular carcinoma cellular lines, for which differentiation versus resistance ability seem to be strongly correlated with well defined types of PPIs, has revealed a promising antiproliferative activity for selected compounds.

Solution Mask Liquid Lithography (SMaLL) for One-Step, Multimaterial 3D Printing.

PubMed

Dolinski, Neil D; Page, Zachariah A; Callaway, E Benjamin; Eisenreich, Fabian; Garcia, Ronnie V; Chavez, Roberto; Bothman, David P; Hecht, Stefan; Zok, Frank W; Hawker, Craig J

2018-06-21

A novel methodology for printing 3D objects with spatially resolved mechanical and chemical properties is reported. Photochromic molecules are used to control polymerization through coherent bleaching fronts, providing large depths of cure and rapid build rates without the need for moving parts. The coupling of these photoswitches with resin mixtures containing orthogonal photo-crosslinking systems allows simultaneous and selective curing of multiple networks, providing access to 3D objects with chemically and mechanically distinct domains. The power of this approach is showcased through the one-step fabrication of bioinspired soft joints and mechanically reinforced "brick-and-mortar" structures. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multiple scaling behaviour and nonlinear traits in music scores

PubMed Central

Larralde, Hernán; Martínez-Mekler, Gustavo; Müller, Markus

2017-01-01

We present a statistical analysis of music scores from different composers using detrended fluctuation analysis (DFA). We find different fluctuation profiles that correspond to distinct autocorrelation structures of the musical pieces. Further, we reveal evidence for the presence of nonlinear autocorrelations by estimating the DFA of the magnitude series, a result validated by a corresponding study of appropriate surrogate data. The amount and the character of nonlinear correlations vary from one composer to another. Finally, we performed a simple experiment in order to evaluate the pleasantness of the musical surrogate pieces in comparison with the original music and find that nonlinear correlations could play an important role in the aesthetic perception of a musical piece. PMID:29308256

Multiple scaling behaviour and nonlinear traits in music scores

NASA Astrophysics Data System (ADS)

González-Espinoza, Alfredo; Larralde, Hernán; Martínez-Mekler, Gustavo; Müller, Markus

2017-12-01

We present a statistical analysis of music scores from different composers using detrended fluctuation analysis (DFA). We find different fluctuation profiles that correspond to distinct autocorrelation structures of the musical pieces. Further, we reveal evidence for the presence of nonlinear autocorrelations by estimating the DFA of the magnitude series, a result validated by a corresponding study of appropriate surrogate data. The amount and the character of nonlinear correlations vary from one composer to another. Finally, we performed a simple experiment in order to evaluate the pleasantness of the musical surrogate pieces in comparison with the original music and find that nonlinear correlations could play an important role in the aesthetic perception of a musical piece.

Conceptual models for cumulative risk assessment.

PubMed

Linder, Stephen H; Sexton, Ken

2011-12-01

In the absence of scientific consensus on an appropriate theoretical framework, cumulative risk assessment and related research have relied on speculative conceptual models. We argue for the importance of theoretical backing for such models and discuss 3 relevant theoretical frameworks, each supporting a distinctive "family" of models. Social determinant models postulate that unequal health outcomes are caused by structural inequalities; health disparity models envision social and contextual factors acting through individual behaviors and biological mechanisms; and multiple stressor models incorporate environmental agents, emphasizing the intermediary role of these and other stressors. The conclusion is that more careful reliance on established frameworks will lead directly to improvements in characterizing cumulative risk burdens and accounting for disproportionate adverse health effects.

Conceptual Models for Cumulative Risk Assessment

PubMed Central

Sexton, Ken

2011-01-01

In the absence of scientific consensus on an appropriate theoretical framework, cumulative risk assessment and related research have relied on speculative conceptual models. We argue for the importance of theoretical backing for such models and discuss 3 relevant theoretical frameworks, each supporting a distinctive “family” of models. Social determinant models postulate that unequal health outcomes are caused by structural inequalities; health disparity models envision social and contextual factors acting through individual behaviors and biological mechanisms; and multiple stressor models incorporate environmental agents, emphasizing the intermediary role of these and other stressors. The conclusion is that more careful reliance on established frameworks will lead directly to improvements in characterizing cumulative risk burdens and accounting for disproportionate adverse health effects. PMID:22021317

Phase-shift detection in a Fourier-transform method for temperature sensing using a tapered fiber microknot resonator.

PubMed

Larocque, Hugo; Lu, Ping; Bao, Xiaoyi

2016-04-01

Phase-shift detection in a fast-Fourier-transform (FFT)-based spectrum analysis technique for temperature sensing using a tapered fiber microknot resonator is proposed and demonstrated. Multiple transmission peaks in the FFT spectrum of the device were identified as optical modes having completed different amounts of round trips within the ring structure. Temperature variation induced phase shifts for each set of peaks were characterized, and experimental results show that different peaks have distinct temperature sensitivities reaching values up to -0.542  rad/°C, which is about 10 times greater than that of a regular adiabatic taper Mach-Zehnder interferometer when using similar phase-tracking schemes.

Overlapping and Divergent Actions of Structurally Distinct Histone Deacetylase Inhibitors in Cardiac Fibroblasts.

PubMed

Schuetze, Katherine B; Stratton, Matthew S; Blakeslee, Weston W; Wempe, Michael F; Wagner, Florence F; Holson, Edward B; Kuo, Yin-Ming; Andrews, Andrew J; Gilbert, Tonya M; Hooker, Jacob M; McKinsey, Timothy A

2017-04-01

Inhibitors of zinc-dependent histone deacetylases (HDACs) profoundly affect cellular function by altering gene expression via changes in nucleosomal histone tail acetylation. Historically, investigators have employed pan-HDAC inhibitors, such as the hydroxamate trichostatin A (TSA), which simultaneously targets members of each of the three zinc-dependent HDAC classes (classes I, II, and IV). More recently, class- and isoform-selective HDAC inhibitors have been developed, providing invaluable chemical biology probes for dissecting the roles of distinct HDACs in the control of various physiologic and pathophysiological processes. For example, the benzamide class I HDAC-selective inhibitor, MGCD0103 [ N -(2-aminophenyl)-4-[[(4-pyridin-3-ylpyrimidin-2-yl)amino]methyl] benzamide], was shown to block cardiac fibrosis, a process involving excess extracellular matrix deposition, which often results in heart dysfunction. Here, we compare the mechanisms of action of structurally distinct HDAC inhibitors in isolated primary cardiac fibroblasts, which are the major extracellular matrix-producing cells of the heart. TSA, MGCD0103, and the cyclic peptide class I HDAC inhibitor, apicidin, exhibited a common ability to enhance histone acetylation, and all potently blocked cardiac fibroblast cell cycle progression. In contrast, MGCD0103, but not TSA or apicidin, paradoxically increased expression of a subset of fibrosis-associated genes. Using the cellular thermal shift assay, we provide evidence that the divergent effects of HDAC inhibitors on cardiac fibroblast gene expression relate to differential engagement of HDAC1- and HDAC2-containing complexes. These findings illustrate the importance of employing multiple compounds when pharmacologically assessing HDAC function in a cellular context and during HDAC inhibitor drug development. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Stereochemical determinants of C-terminal specificity in PDZ peptide-binding domains: a novel contribution of the carboxylate-binding loop.

PubMed

Amacher, Jeanine F; Cushing, Patrick R; Bahl, Christopher D; Beck, Tobias; Madden, Dean R

2013-02-15

PDZ (PSD-95/Dlg/ZO-1) binding domains often serve as cellular traffic engineers, controlling the localization and activity of a wide variety of binding partners. As a result, they play important roles in both physiological and pathological processes. However, PDZ binding specificities overlap, allowing multiple PDZ proteins to mediate distinct effects on shared binding partners. For example, several PDZ domains bind the cystic fibrosis (CF) transmembrane conductance regulator (CFTR), an epithelial ion channel mutated in CF. Among these binding partners, the CFTR-associated ligand (CAL) facilitates post-maturational degradation of the channel and is thus a potential therapeutic target. Using iterative optimization, we previously developed a selective CAL inhibitor peptide (iCAL36). Here, we investigate the stereochemical basis of iCAL36 specificity. The crystal structure of iCAL36 in complex with the CAL PDZ domain reveals stereochemical interactions distributed along the peptide-binding cleft, despite the apparent degeneracy of the CAL binding motif. A critical selectivity determinant that distinguishes CAL from other CFTR-binding PDZ domains is the accommodation of an isoleucine residue at the C-terminal position (P(0)), a characteristic shared with the Tax-interacting protein-1. Comparison of the structures of these two PDZ domains in complex with ligands containing P(0) Leu or Ile residues reveals two distinct modes of accommodation for β-branched C-terminal side chains. Access to each mode is controlled by distinct residues in the carboxylate-binding loop. These studies provide new insights into the primary sequence determinants of binding motifs, which in turn control the scope and evolution of PDZ interactomes.

Muscles innervated by a single motor neuron exhibit divergent synaptic properties on multiple time scales.

PubMed

Blitz, Dawn M; Pritchard, Amy E; Latimer, John K; Wakefield, Andrew T

2017-04-01

Adaptive changes in the output of neural circuits underlying rhythmic behaviors are relayed to muscles via motor neuron activity. Presynaptic and postsynaptic properties of neuromuscular junctions can impact the transformation from motor neuron activity to muscle response. Further, synaptic plasticity occurring on the time scale of inter-spike intervals can differ between multiple muscles innervated by the same motor neuron. In rhythmic behaviors, motor neuron bursts can elicit additional synaptic plasticity. However, it is unknown whether plasticity regulated by the longer time scale of inter-burst intervals also differs between synapses from the same neuron, and whether any such distinctions occur across a physiological activity range. To address these issues, we measured electrical responses in muscles innervated by a chewing circuit neuron, the lateral gastric (LG) motor neuron, in a well-characterized small motor system, the stomatogastric nervous system (STNS) of the Jonah crab, Cancer borealis In vitro and in vivo , sensory, hormonal and modulatory inputs elicit LG bursting consisting of inter-spike intervals of 50-250 ms and inter-burst intervals of 2-24 s. Muscles expressed similar facilitation measured with paired stimuli except at the shortest inter-spike interval. However, distinct decay time constants resulted in differences in temporal summation. In response to bursting activity, augmentation occurred to different extents and saturated at different inter-burst intervals. Further, augmentation interacted with facilitation, resulting in distinct intra-burst facilitation between muscles. Thus, responses of multiple target muscles diverge across a physiological activity range as a result of distinct synaptic properties sensitive to multiple time scales. © 2017. Published by The Company of Biologists Ltd.

Object similarity affects the perceptual strategy underlying invariant visual object recognition in rats

PubMed Central

Rosselli, Federica B.; Alemi, Alireza; Ansuini, Alessio; Zoccolan, Davide

2015-01-01

In recent years, a number of studies have explored the possible use of rats as models of high-level visual functions. One central question at the root of such an investigation is to understand whether rat object vision relies on the processing of visual shape features or, rather, on lower-order image properties (e.g., overall brightness). In a recent study, we have shown that rats are capable of extracting multiple features of an object that are diagnostic of its identity, at least when those features are, structure-wise, distinct enough to be parsed by the rat visual system. In the present study, we have assessed the impact of object structure on rat perceptual strategy. We trained rats to discriminate between two structurally similar objects, and compared their recognition strategies with those reported in our previous study. We found that, under conditions of lower stimulus discriminability, rat visual discrimination strategy becomes more view-dependent and subject-dependent. Rats were still able to recognize the target objects, in a way that was largely tolerant (i.e., invariant) to object transformation; however, the larger structural and pixel-wise similarity affected the way objects were processed. Compared to the findings of our previous study, the patterns of diagnostic features were: (i) smaller and more scattered; (ii) only partially preserved across object views; and (iii) only partially reproducible across rats. On the other hand, rats were still found to adopt a multi-featural processing strategy and to make use of part of the optimal discriminatory information afforded by the two objects. Our findings suggest that, as in humans, rat invariant recognition can flexibly rely on either view-invariant representations of distinctive object features or view-specific object representations, acquired through learning. PMID:25814936

Bifurcation of potential vorticity gradients across the Southern Hemisphere stratospheric polar vortex

NASA Astrophysics Data System (ADS)

Conway, Jonathan; Bodeker, Greg; Cameron, Chris

2018-06-01

The wintertime stratospheric westerly winds circling the Antarctic continent, also known as the Southern Hemisphere polar vortex, create a barrier to mixing of air between middle and high latitudes. This dynamical isolation has important consequences for export of ozone-depleted air from the Antarctic stratosphere to lower latitudes. The prevailing view of this dynamical barrier has been an annulus compromising steep gradients of potential vorticity (PV) that create a single semi-permeable barrier to mixing. Analyses presented here show that this barrier often displays a bifurcated structure where a double-walled barrier exists. The bifurcated structure manifests as enhanced gradients of PV at two distinct latitudes - usually on the inside and outside flanks of the region of highest wind speed. Metrics that quantify the bifurcated nature of the vortex have been developed and their variation in space and time has been analysed. At most isentropic levels between 395 and 850 K, bifurcation is strongest in mid-winter and decreases dramatically during spring. From August onwards a distinct structure emerges, where elevated bifurcation remains between 475 and 600 K, and a mostly single-walled barrier occurs at other levels. While bifurcation at a given level evolves from month to month, and does not always persist through a season, interannual variations in the strength of bifurcation display coherence across multiple levels in any given month. Accounting for bifurcation allows the region of reduced mixing to be better characterised. These results suggest that improved understanding of cross-vortex mixing requires consideration of the polar vortex not as a single mixing barrier but as a barrier with internal structure that is likely to manifest as more complex gradients in trace gas concentrations across the vortex barrier region.

Maximum likelihood Bayesian model averaging and its predictive analysis for groundwater reactive transport models

USGS Publications Warehouse

Curtis, Gary P.; Lu, Dan; Ye, Ming

2015-01-01

While Bayesian model averaging (BMA) has been widely used in groundwater modeling, it is infrequently applied to groundwater reactive transport modeling because of multiple sources of uncertainty in the coupled hydrogeochemical processes and because of the long execution time of each model run. To resolve these problems, this study analyzed different levels of uncertainty in a hierarchical way, and used the maximum likelihood version of BMA, i.e., MLBMA, to improve the computational efficiency. This study demonstrates the applicability of MLBMA to groundwater reactive transport modeling in a synthetic case in which twenty-seven reactive transport models were designed to predict the reactive transport of hexavalent uranium (U(VI)) based on observations at a former uranium mill site near Naturita, CO. These reactive transport models contain three uncertain model components, i.e., parameterization of hydraulic conductivity, configuration of model boundary, and surface complexation reactions that simulate U(VI) adsorption. These uncertain model components were aggregated into the alternative models by integrating a hierarchical structure into MLBMA. The modeling results of the individual models and MLBMA were analyzed to investigate their predictive performance. The predictive logscore results show that MLBMA generally outperforms the best model, suggesting that using MLBMA is a sound strategy to achieve more robust model predictions relative to a single model. MLBMA works best when the alternative models are structurally distinct and have diverse model predictions. When correlation in model structure exists, two strategies were used to improve predictive performance by retaining structurally distinct models or assigning smaller prior model probabilities to correlated models. Since the synthetic models were designed using data from the Naturita site, the results of this study are expected to provide guidance for real-world modeling. Limitations of applying MLBMA to the synthetic study and future real-world modeling are discussed.

Two Perspectives on Proportional Relationships: Extending Complementary Origins of Multiplication in Terms of Quantities

ERIC Educational Resources Information Center

Beckmann, Sybilla; Izsák, Andrew

2015-01-01

In this article, we present a mathematical analysis that distinguishes two distinct quantitative perspectives on ratios and proportional relationships: variable number of fixed quantities and fixed numbers of variable parts. This parallels the distinction between measurement and partitive meanings for division and between two meanings for…

A Case Study of Two Groups of Elementary Prospective Teachers' Experiences in Distinct Mathematics Content Courses

ERIC Educational Resources Information Center

Auslander, Susan Swars; Smith, Stephanie Z.; Smith, Marvin E.; Hart, Lynn C.; Carothers, Jody

2016-01-01

This multiple case study examined two groups of elementary prospective teachers (n=12) completing distinct mathematics content courses. Data were collected via two belief surveys, one content knowledge assessment, and individual interviews. The findings revealed differences in specialized content knowledge and mathematical beliefs between the two…

Comparison of Radio Frequency Distinct Native Attribute and Matched Filtering Techniques for Device Discrimination and Operation Identification

DTIC Science & Technology

identification. URE from ten MSP430F5529 16-bit microcontrollers were analyzed using: 1) RF distinct native attributes (RF-DNA) fingerprints paired with multiple...discriminant analysis/maximum likelihood (MDA/ML) classification, 2) RF-DNA fingerprints paired with generalized relevance learning vector quantized

Multiple nuclear loci reveal the distinctiveness of the threatened, Neotropical Pinus chiapensis

Treesearch

John Syring; Rafael F. del Castillo; Richard Cronn; Aaron Liston

2007-01-01

Pinus chiapensis is a threatened species of pine from southern Mexico and Guatemala. It was first described as a disjunct variety of P. strobus from the eastern United States and Canada. Subsequent morphological work indicates that P. chinpensis is a distinct species, but this interpretation is controversial. To...

The iFlow modelling framework v2.4: a modular idealized process-based model for flow and transport in estuaries

NASA Astrophysics Data System (ADS)

Dijkstra, Yoeri M.; Brouwer, Ronald L.; Schuttelaars, Henk M.; Schramkowski, George P.

2017-07-01

The iFlow modelling framework is a width-averaged model for the systematic analysis of the water motion and sediment transport processes in estuaries and tidal rivers. The distinctive solution method, a mathematical perturbation method, used in the model allows for identification of the effect of individual physical processes on the water motion and sediment transport and study of the sensitivity of these processes to model parameters. This distinction between processes provides a unique tool for interpreting and explaining hydrodynamic interactions and sediment trapping. iFlow also includes a large number of options to configure the model geometry and multiple choices of turbulence and salinity models. Additionally, the model contains auxiliary components, including one that facilitates easy and fast sensitivity studies. iFlow has a modular structure, which makes it easy to include, exclude or change individual model components, called modules. Depending on the required functionality for the application at hand, modules can be selected to construct anything from very simple quasi-linear models to rather complex models involving multiple non-linear interactions. This way, the model complexity can be adjusted to the application. Once the modules containing the required functionality are selected, the underlying model structure automatically ensures modules are called in the correct order. The model inserts iteration loops over groups of modules that are mutually dependent. iFlow also ensures a smooth coupling of modules using analytical and numerical solution methods. This way the model combines the speed and accuracy of analytical solutions with the versatility of numerical solution methods. In this paper we present the modular structure, solution method and two examples of the use of iFlow. In the examples we present two case studies, of the Yangtze and Scheldt rivers, demonstrating how iFlow facilitates the analysis of model results, the understanding of the underlying physics and the testing of parameter sensitivity. A comparison of the model results to measurements shows a good qualitative agreement. iFlow is written in Python and is available as open source code under the LGPL license.

A Modular Approach to Arithmetic and Logic Unit Design on a Reconfigurable Hardware Platform for Educational Purpose

NASA Astrophysics Data System (ADS)

Oztekin, Halit; Temurtas, Feyzullah; Gulbag, Ali

The Arithmetic and Logic Unit (ALU) design is one of the important topics in Computer Architecture and Organization course in Computer and Electrical Engineering departments. There are ALU designs that have non-modular nature to be used as an educational tool. As the programmable logic technology has developed rapidly, it is feasible that ALU design based on Field Programmable Gate Array (FPGA) is implemented in this course. In this paper, we have adopted the modular approach to ALU design based on FPGA. All the modules in the ALU design are realized using schematic structure on Altera's Cyclone II Development board. Under this model, the ALU content is divided into four distinct modules. These are arithmetic unit except for multiplication and division operations, logic unit, multiplication unit and division unit. User can easily design any size of ALU unit since this approach has the modular nature. Then, this approach was applied to microcomputer architecture design named BZK.SAU.FPGA10.0 instead of the current ALU unit.

Multiple mechanisms generate a universal scaling with dissipation for the air-water gas transfer velocity

NASA Astrophysics Data System (ADS)

Katul, Gabriel; Liu, Heping

2017-02-01

A large corpus of field and laboratory experiments support the finding that the water side transfer velocity kL of sparingly soluble gases near air-water interfaces scales as kL˜(νɛ)1/4, where ν is the kinematic water viscosity and ɛ is the mean turbulent kinetic energy dissipation rate. Originally predicted from surface renewal theory, this scaling appears to hold for marine and coastal systems and across many environmental conditions. It is shown that multiple approaches to representing the effects of turbulence on kL lead to this expression when the Kolmogorov microscale is assumed to be the most efficient transporting eddy near the interface. The approaches considered range from simplified surface renewal schemes with distinct models for renewal durations, scaling and dimensional considerations, and a new structure function approach derived using analogies between scalar and momentum transfer. The work offers a new perspective as to why the aforementioned 1/4 scaling is robust.

A tentative framework for the acquisition of language and modern human cognition.

PubMed

Tattersall, Ian

2016-06-20

Modern human beings process information symbolically, rearranging mental symbols to envision multiple potential realities. They also express the ideas they form using structured articulate language. No other living creature does either of these things. Yet it is evident that we are descended from a non-symbolic and non-linguistic ancestor. How did this astonishing transformation occur? Scrutiny of the fossil and archaeological records reveals that the transition to symbolic reasoning happened very late in hominid history - indeed, within the tenure of anatomically recognizable Homo sapiens. It was evidently not simply a passive result of the increase in brain size that typified multiple lineages of the genus Homo over the Pleistocene. Instead, a brain exaptively capable of complex symbolic manipulation and language acquisition was acquired in the major developmental reorganization that gave rise to the anatomically distinctive species Homo sapiens. The new capacity it conferred was later recruited through the action of a cultural stimulus, most plausibly the spontaneous invention of language.

Reconstruction and topological characterization of the sigma factor regulatory network of Mycobacterium tuberculosis

PubMed Central

Chauhan, Rinki; Ravi, Janani; Datta, Pratik; Chen, Tianlong; Schnappinger, Dirk; Bassler, Kevin E.; Balázsi, Gábor; Gennaro, Maria Laura

2016-01-01

Accessory sigma factors, which reprogram RNA polymerase to transcribe specific gene sets, activate bacterial adaptive responses to noxious environments. Here we reconstruct the complete sigma factor regulatory network of the human pathogen Mycobacterium tuberculosis by an integrated approach. The approach combines identification of direct regulatory interactions between M. tuberculosis sigma factors in an E. coli model system, validation of selected links in M. tuberculosis, and extensive literature review. The resulting network comprises 41 direct interactions among all 13 sigma factors. Analysis of network topology reveals (i) a three-tiered hierarchy initiating at master regulators, (ii) high connectivity and (iii) distinct communities containing multiple sigma factors. These topological features are likely associated with multi-layer signal processing and specialized stress responses involving multiple sigma factors. Moreover, the identification of overrepresented network motifs, such as autoregulation and coregulation of sigma and anti-sigma factor pairs, provides structural information that is relevant for studies of network dynamics. PMID:27029515

College drinking behaviors: mediational links between parenting styles, parental bonds, depression, and alcohol problems.

PubMed

Patock-Peckham, Julie A; Morgan-Lopez, Antonio A

2007-09-01

Mediational links between parenting styles (authoritative, authoritarian, permissive), parental bond (positive, negative), depression, alcohol use and abuse were tested. A 2-group, multiple-indicator, multiple-cause structural equation model with 441 (216 female, 225 male) college students was examined. In general, a poor parental bond with one's father was highly predictive of depression, a well-known predictor of alcohol abuse and related problems for both genders. In contrast, a positive parental bond with one's father significantly mediated the positive effects of authoritative fathering on depression, which then decreased alcohol use problems for both genders. For women, a negative parental bond with one's father significantly mediated the effect of having an authoritarian father on depression, which increased alcohol use problems. These findings suggest that parental influences on pathways to alcohol abuse through depression (primarily through fathers for both genders) are distinct from pathways stemming from poor impulse control (with influences primarily from the same-sex parents for both genders).

High frequency, spontaneous motA mutations in Campylobacter jejuni strain 81-176.

PubMed

Mohawk, Krystle L; Poly, Frédéric; Sahl, Jason W; Rasko, David A; Guerry, Patricia

2014-01-01

Campylobacter jejuni is an important cause of bacterial diarrhea worldwide. The pathogenesis of C. jejuni is poorly understood and complicated by phase variation of multiple surface structures including lipooligosaccharide, capsule, and flagellum. When C. jejuni strain 81-176 was plated on blood agar for single colonies, the presence of translucent, non-motile colonial variants was noted among the majority of opaque, motile colonies. High-throughput genomic sequencing of two flagellated translucent and two opaque variants as well as the parent strain revealed multiple genetic changes compared to the published genome. However, the only mutated open reading frame common between the two translucent variants and absent from the opaque variants and the parent was motA, encoding a flagellar motor protein. A total of 18 spontaneous motA mutations were found that mapped to four distinct sites in the gene, with only one class of mutation present in a phase variable region. This study exemplifies the mutative/adaptive properties of C. jejuni and demonstrates additional variability in C. jejuni beyond phase variation.

The Cryptococcus neoformans Capsule: a Sword and a Shield

PubMed Central

O'Meara, Teresa R.

2012-01-01

Summary: The human fungal pathogen Cryptococcus neoformans is characterized by its ability to induce a distinct polysaccharide capsule in response to a number of host-specific environmental stimuli. The induction of capsule is a complex biological process encompassing regulation at multiple steps, including the biosynthesis, transport, and maintenance of the polysaccharide at the cell surface. By precisely regulating the composition of its cell surface and secreted polysaccharides, C. neoformans has developed intricate ways to establish chronic infection and dormancy in the human host. The plasticity of the capsule structure in response to various host conditions also underscores the complex relationship between host and parasite. Much of this precise regulation of capsule is achieved through the transcriptional responses of multiple conserved signaling pathways that have been coopted to regulate this C. neoformans-specific virulence-associated phenotype. This review focuses on specific host stimuli that trigger the activation of the signal transduction cascades and on the downstream transcriptional responses that are required for robust encapsulation around the cell. PMID:22763631

Concerted Dynamic Motions of an FABP4 Model and Its Ligands Revealed by Microsecond Molecular Dynamics Simulations

PubMed Central

2015-01-01

In this work, we investigate the dynamic motions of fatty acid binding protein 4 (FABP4) in the absence and presence of a ligand by explicitly solvated all-atom molecular dynamics simulations. The dynamics of one ligand-free FABP4 and four ligand-bound FABP4s is compared via multiple 1.2 μs simulations. In our simulations, the protein interconverts between the open and closed states. Ligand-free FABP4 prefers the closed state, whereas ligand binding induces a conformational transition to the open state. Coupled with opening and closing of FABP4, the ligand adopts distinct binding modes, which are identified and compared with crystal structures. The concerted dynamics of protein and ligand suggests that there may exist multiple FABP4–ligand binding conformations. Thus, this work provides details about how ligand binding affects the conformational preference of FABP4 and how ligand binding is coupled with a conformational change of FABP4 at an atomic level. PMID:25231537

Concerted dynamic motions of an FABP4 model and its ligands revealed by microsecond molecular dynamics simulations.

PubMed

Li, Yan; Li, Xiang; Dong, Zigang

2014-10-14

In this work, we investigate the dynamic motions of fatty acid binding protein 4 (FABP4) in the absence and presence of a ligand by explicitly solvated all-atom molecular dynamics simulations. The dynamics of one ligand-free FABP4 and four ligand-bound FABP4s is compared via multiple 1.2 μs simulations. In our simulations, the protein interconverts between the open and closed states. Ligand-free FABP4 prefers the closed state, whereas ligand binding induces a conformational transition to the open state. Coupled with opening and closing of FABP4, the ligand adopts distinct binding modes, which are identified and compared with crystal structures. The concerted dynamics of protein and ligand suggests that there may exist multiple FABP4-ligand binding conformations. Thus, this work provides details about how ligand binding affects the conformational preference of FABP4 and how ligand binding is coupled with a conformational change of FABP4 at an atomic level.

The Relationship of Hypochondriasis to Anxiety, Depressive, and Somatoform Disorders

PubMed Central

Scarella, Timothy M.; Laferton, Johannes A. C.; Ahern, David K.; Fallon, Brian A.; Barsky, Arthur

2015-01-01

Background Though the phenotype of anxiety about medical illness has long been recognized, there continues to be debate as to whether it is a distinct psychiatric disorder and, if so, to which diagnostic category it belongs. Our objective was to investigate the pattern of psychiatric co-morbidity in hypochondriasis and to assess the relationship of health anxiety to anxiety, depressive, and somatoform disorders. Methods Data were collected as part of a clinical trial on treatment methods for hypochondriasis. 194 participants meeting criteria for DSM-IV hypochondriasis were assessed by sociodemographic variables, results of structured diagnostic interviews, and validated instruments for assessing various symptom dimensions of psychopathology. Results The majority of individuals with hypochondriasis had co-morbid psychiatric illness; the mean number of co-morbid diagnoses was 1.4, and 35.1% had hypochondriasis as their only diagnosis. Participants were more likely to have only co-morbid anxiety disorders than only co-morbid depressive or somatoform disorders. Multiple regression analysis of continuous measures of symptoms revealed the strongest correlation of health anxiety with anxiety symptoms, and a weaker correlation with somatoform symptoms; in multiple regression analysis, there was no correlation between health anxiety and depressive symptoms. Conclusion Our findings suggest that the entity of health anxiety (Hypochondriasis in DSM-IV, Illness Anxiety Disorder in DSM-5) is a clinical syndrome distinct from other psychiatric disorders. Analysis of co-morbidity patterns and continuous measures of symptoms suggest its appropriate classification is with anxiety rather than somatoform or mood disorders. PMID:26785798

Novel TDP2-ubiquitin interactions and their importance for the repair of topoisomerase II-mediated DNA damage

PubMed Central

Rao, Timsi; Gao, Rui; Takada, Saeko; Al Abo, Muthana; Chen, Xiang; Walters, Kylie J.; Pommier, Yves; Aihara, Hideki

2016-01-01

Tyrosyl DNA phosphodiesterase 2 (TDP2) is a multifunctional protein implicated in DNA repair, signal transduction and transcriptional regulation. In its DNA repair role, TDP2 safeguards genome integrity by hydrolyzing 5′-tyrosyl DNA adducts formed by abortive topoisomerase II (Top2) cleavage complexes to allow error-free repair of DNA double-strand breaks, thereby conferring cellular resistance against Top2 poisons. TDP2 consists of a C-terminal catalytic domain responsible for its phosphodiesterase activity, and a functionally uncharacterized N-terminal region. Here, we demonstrate that this N-terminal region contains a ubiquitin (Ub)-associated (UBA) domain capable of binding multiple forms of Ub with distinct modes of interactions and preference for either K48- or K63-linked polyUbs over monoUb. The structure of TDP2 UBA bound to monoUb shows a canonical mode of UBA-Ub interaction. However, the absence of the highly conserved MGF motif and the presence of a fourth α-helix make TDP2 UBA distinct from other known UBAs. Mutations in the TDP2 UBA-Ub binding interface do not affect nuclear import of TDP2, but severely compromise its ability to repair Top2-mediated DNA damage, thus establishing the importance of the TDP2 UBA–Ub interaction in DNA repair. The differential binding to multiple Ub forms could be important for responding to DNA damage signals under different contexts or to support the multi-functionality of TDP2. PMID:27543075

Leveraging structure determination with fragment screening for infectious disease drug targets: MECP synthase from Burkholderia pseudomallei

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

Begley, Darren W.; Hartley, Robert C.; Davies, Douglas R.

As part of the Seattle Structural Genomics Center for Infectious Disease, we seek to enhance structural genomics with ligand-bound structure data which can serve as a blueprint for structure-based drug design. We have adapted fragment-based screening methods to our structural genomics pipeline to generate multiple ligand-bound structures of high priority drug targets from pathogenic organisms. In this study, we report fragment screening methods and structure determination results for 2C-methyl-D-erythritol-2,4-cyclo-diphosphate (MECP) synthase from Burkholderia pseudomallei, the gram-negative bacterium which causes melioidosis. Screening by nuclear magnetic resonance spectroscopy as well as crystal soaking followed by X-ray diffraction led to the identification ofmore » several small molecules which bind this enzyme in a critical metabolic pathway. A series of complex structures obtained with screening hits reveal distinct binding pockets and a range of small molecules which form complexes with the target. Additional soaks with these compounds further demonstrate a subset of fragments to only bind the protein when present in specific combinations. This ensemble of fragment-bound complexes illuminates several characteristics of MECP synthase, including a previously unknown binding surface external to the catalytic active site. These ligand-bound structures now serve to guide medicinal chemists and structural biologists in rational design of novel inhibitors for this enzyme.« less

Identification and characterization of a class of MALAT1 -like genomic loci

DOE PAGES

Zhang, Bin; Mao, Yuntao S.; Diermeier, Sarah D.; ...

2017-05-23

The MALAT1 (Metastasis-Associated Lung Adenocarcinoma Transcript 1) gene encodes a noncoding RNA that is processed into a long nuclear retained transcript ( MALAT1) and a small cytoplasmic tRNA-like transcript (mascRNA). Using an RNA sequence- and structure-based covariance model, we identified more than 130 genomic loci in vertebrate genomes containing the MALAT1 3' end triple-helix structure and its immediate downstream tRNA-like structure, including 44 in the green lizard Anolis carolinensis. Structural and computational analyses revealed a co-occurrence of components of the 3' end module. MALAT1-like genes in Anolis carolinensis are highly expressed in adult testis, thus we named them testis-abundant longmore » noncoding RNAs (tancRNAs). MALAT1-like loci also produce multiple small RNA species, including PIWI-interacting RNAs (piRNAs), from the antisense strand. The 3' ends of tancRNAs serve as potential targets for the PIWI-piRNA complex. Furthermore, we have identified an evolutionarily conserved class of long noncoding RNAs (lncRNAs) with similar structural constraints, post-transcriptional processing, and subcellular localization and a distinct function in spermatocytes.« less

Identification and characterization of a class of MALAT1 -like genomic loci

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

Zhang, Bin; Mao, Yuntao S.; Diermeier, Sarah D.

The MALAT1 (Metastasis-Associated Lung Adenocarcinoma Transcript 1) gene encodes a noncoding RNA that is processed into a long nuclear retained transcript ( MALAT1) and a small cytoplasmic tRNA-like transcript (mascRNA). Using an RNA sequence- and structure-based covariance model, we identified more than 130 genomic loci in vertebrate genomes containing the MALAT1 3' end triple-helix structure and its immediate downstream tRNA-like structure, including 44 in the green lizard Anolis carolinensis. Structural and computational analyses revealed a co-occurrence of components of the 3' end module. MALAT1-like genes in Anolis carolinensis are highly expressed in adult testis, thus we named them testis-abundant longmore » noncoding RNAs (tancRNAs). MALAT1-like loci also produce multiple small RNA species, including PIWI-interacting RNAs (piRNAs), from the antisense strand. The 3' ends of tancRNAs serve as potential targets for the PIWI-piRNA complex. Furthermore, we have identified an evolutionarily conserved class of long noncoding RNAs (lncRNAs) with similar structural constraints, post-transcriptional processing, and subcellular localization and a distinct function in spermatocytes.« less

Chemical and Conformational Diversity of Modified Nucleosides Affects tRNA Structure and Function.

PubMed

Väre, Ville Y P; Eruysal, Emily R; Narendran, Amithi; Sarachan, Kathryn L; Agris, Paul F

2017-03-16

RNAs are central to all gene expression through the control of protein synthesis. Four major nucleosides, adenosine, guanosine, cytidine and uridine, compose RNAs and provide sequence variation, but are limited in contributions to structural variation as well as distinct chemical properties. The ability of RNAs to play multiple roles in cellular metabolism is made possible by extensive variation in length, conformational dynamics, and the over 100 post-transcriptional modifications. There are several reviews of the biochemical pathways leading to RNA modification, but the physicochemical nature of modified nucleosides and how they facilitate RNA function is of keen interest, particularly with regard to the contributions of modified nucleosides. Transfer RNAs (tRNAs) are the most extensively modified RNAs. The diversity of modifications provide versatility to the chemical and structural environments. The added chemistry, conformation and dynamics of modified nucleosides occurring at the termini of stems in tRNA's cloverleaf secondary structure affect the global three-dimensional conformation, produce unique recognition determinants for macromolecules to recognize tRNAs, and affect the accurate and efficient decoding ability of tRNAs. This review will discuss the impact of specific chemical moieties on the structure, stability, electrochemical properties, and function of tRNAs.

Crystal Structure of the Oligomeric Form of Lassa Virus Matrix Protein Z.

PubMed

Hastie, Kathryn M; Zandonatti, Michelle; Liu, Tong; Li, Sheng; Woods, Virgil L; Saphire, Erica Ollmann

2016-05-01

The arenavirus matrix protein Z is highly multifunctional and occurs in both monomeric and oligomeric forms. The crystal structure of a dodecamer of Z from Lassa virus, presented here, illustrates a ring-like structure with a highly basic center. Mutagenesis demonstrates that the dimeric interface within the dodecamer and a Lys-Trp-Lys triad at the center of the ring are important for oligomerization. This structure provides an additional template to explore the many functions of Z. The arenavirus Lassa virus causes hundreds of thousands of infections each year, many of which develop into fatal hemorrhagic fever. The arenavirus matrix protein Z is multifunctional, with at least four distinct roles. Z exists in both monomeric and oligomeric forms, each of which likely serves a specific function in the viral life cycle. Here we present the dodecameric form of Lassa virus Z and demonstrate that Z forms a "wreath" with a highly basic center. This structure and that of monomeric Z now provide a pair of critical templates by which the multiple roles of Z in the viral life cycle may be interpreted. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Mangrove vegetation structure in Southeast Brazil from phased array L-band synthetic aperture radar data

NASA Astrophysics Data System (ADS)

de Souza Pereira, Francisca Rocha; Kampel, Milton; Cunha-Lignon, Marilia

2016-07-01

The potential use of phased array type L-band synthetic aperture radar (PALSAR) data for discriminating distinct physiographic mangrove types with different forest structure developments in a subtropical mangrove forest located in Cananéia on the Southern coast of São Paulo, Brazil, is investigated. The basin and fringe physiographic types and the structural development of mangrove vegetation were identified with the application of the Kruskal-Wallis statistical test to the SAR backscatter values of 10 incoherent attributes. The best results to separate basin to fringe types were obtained using copolarized HH, cross-polarized HV, and the biomass index (BMI). Mangrove structural parameters were also estimated using multiple linear regressions. BMI and canopy structure index were used as explanatory variables for canopy height, mean height, and mean diameter at breast height regression models, with significant R2=0.69, 0.73, and 0.67, respectively. The current study indicates that SAR L-band images can be used as a tool to discriminate physiographic types and to characterize mangrove forests. The results are relevant considering the crescent availability of freely distributed SAR images that can be more utilized for analysis, monitoring, and conservation of the mangrove ecosystem.

An Analysis of Cassini Observations Regarding the Structure of Jupiter's Equatorial Atmosphere

NASA Technical Reports Server (NTRS)

Choi, David S.; Simon-Miller, Amy A.

2012-01-01

A variety of intriguing atmospheric phenomena reside on both sides of Jupiter's equator. 5-micron bright hot spots and opaque plumes prominently exhibit dynamic behavior to the north, whereas compact, dark chevron-shaped features and isolated anticyclonic disturbances periodically occupy the southern equatorial latitudes. All of these phenomena are associated with the vertical and meridional perturbations of Rossby waves disturbing the mean atmospheric state. As previous observational analysis and numerical simulations have investigated the dynamics of the region, an examination of the atmosphere's vertical structure though radiative transfer analysis is necessary for improved understanding of this unique environment. Here we present preliminary analysis of a multispectral Cassini imaging data set acquired during the spacecraft's flyby of Jupiter in 2000. We evaluated multiple methane and continuum spectral channels at available viewing angles to improve constraints on the vertical structure of the haze and cloud layers comprising these interesting features. Our preliminary results indicate distinct differences in the structure for both hemispheres. Upper troposphere hazes and cloud layers are prevalent in the northern equatorial latitudes, but are not present in corresponding southern latitudes. Continued analysis will further constrain the precise structure present in these phenomena and the differences between them.

A theory of self-organized zonal flow with fine radial structure in tokamak

NASA Astrophysics Data System (ADS)

Zhang, Y. Z.; Liu, Z. Y.; Xie, T.; Mahajan, S. M.; Liu, J.

2017-12-01

The (low frequency) zonal flow-ion temperature gradient (ITG) wave system, constructed on Braginskii's fluid model in tokamak, is shown to be a reaction-diffusion-advection system; it is derived by making use of a multiple spatiotemporal scale technique and two-dimensional (2D) ballooning theory. For real regular group velocities of ITG waves, two distinct temporal processes, sharing a very similar meso-scale radial structure, are identified in the nonlinear self-organized stage. The stationary and quasi-stationary structures reflect a particular feature of the poloidal group velocity. The equation set posed to be an initial value problem is numerically solved for JET low mode parameters; the results are presented in several figures and two movies that show the spatiotemporal evolutions as well as the spectrum analysis—frequency-wave number spectrum, auto power spectrum, and Lissajous diagram. This approach reveals that the zonal flow in tokamak is a local traveling wave. For the quasi-stationary process, the cycle of ITG wave energy is composed of two consecutive phases in distinct spatiotemporal structures: a pair of Cavitons growing and breathing slowly without long range propagation, followed by a sudden decay into many Instantons that carry negative wave energy rapidly into infinity. A spotlight onto the motion of Instantons for a given radial position reproduces a Blob-Hole temporal structure; the occurrence as well as the rapid decay of Caviton into Instantons is triggered by zero-crossing of radial group velocity. A sample of the radial profile of zonal flow contributed from 31 nonlinearly coupled rational surfaces near plasma edge is found to be very similar to that observed in the JET Ohmic phase [J. C. Hillesheim et al., Phys. Rev. Lett. 116, 165002 (2016)]. The theory predicts an interior asymmetric dipole structure associated with the zonal flow that is driven by the gradients of ITG turbulence intensity.

Limited Pollen Dispersal Contributes to Population Genetic Structure but Not Local Adaptation in Quercus oleoides Forests of Costa Rica.

PubMed

Deacon, Nicholas John; Cavender-Bares, Jeannine

2015-01-01

Quercus oleoides Cham. and Schlect., tropical live oak, is a species of conservation importance in its southern range limit of northwestern Costa Rica. It occurs in high-density stands across a fragmented landscape spanning a contrasting elevation and precipitation gradient. We examined genetic diversity and spatial genetic structure in this geographically isolated and genetically distinct population. We characterized population genetic diversity at 11 nuclear microsatellite loci in 260 individuals from 13 sites. We monitored flowering time at 10 sites, and characterized the local environment in order to compare observed spatial genetic structure to hypotheses of isolation-by-distance and isolation-by-environment. Finally, we quantified pollen dispersal distances and tested for local adaptation through a reciprocal transplant experiment in order to experimentally address these hypotheses. High genetic diversity is maintained in the population and the genetic variation is significantly structured among sampled sites. We identified 5 distinct genetic clusters and average pollen dispersal predominately occurred over short distances. Differences among sites in flowering phenology and environmental factors, however, were not strictly associated with genetic differentiation. Growth and survival of upland and lowland progeny in their native and foreign environments was expected to exhibit evidence of local adaptation due to the more extreme dry season in the lowlands. Seedlings planted in the lowland garden experienced much higher mortality than seedlings in the upland garden, but we did not identify evidence for local adaptation. Overall, this study indicates that the Costa Rican Q. oleoides population has a rich population genetic history. Despite environmental heterogeneity and habitat fragmentation, isolation-by-distance and isolation-by-environment alone do not explain spatial genetic structure. These results add to studies of genetic structure by examining a common, tropical tree over multiple habitats and provide information for managers of a successional forest in a protected area.

BowMapCL: Burrows-Wheeler Mapping on Multiple Heterogeneous Accelerators.

PubMed

Nogueira, David; Tomas, Pedro; Roma, Nuno

2016-01-01

The computational demand of exact-search procedures has pressed the exploitation of parallel processing accelerators to reduce the execution time of many applications. However, this often imposes strict restrictions in terms of the problem size and implementation efforts, mainly due to their possibly distinct architectures. To circumvent this limitation, a new exact-search alignment tool (BowMapCL) based on the Burrows-Wheeler Transform and FM-Index is presented. Contrasting to other alternatives, BowMapCL is based on a unified implementation using OpenCL, allowing the exploitation of multiple and possibly different devices (e.g., NVIDIA, AMD/ATI, and Intel GPUs/APUs). Furthermore, to efficiently exploit such heterogeneous architectures, BowMapCL incorporates several techniques to promote its performance and scalability, including multiple buffering, work-queue task-distribution, and dynamic load-balancing, together with index partitioning, bit-encoding, and sampling. When compared with state-of-the-art tools, the attained results showed that BowMapCL (using a single GPU) is 2 × to 7.5 × faster than mainstream multi-threaded CPU BWT-based aligners, like Bowtie, BWA, and SOAP2; and up to 4 × faster than the best performing state-of-the-art GPU implementations (namely, SOAP3 and HPG-BWT). When multiple and completely distinct devices are considered, BowMapCL efficiently scales the offered throughput, ensuring a convenient load-balance of the involved processing in the several distinct devices.

Identifying multiple coral reef regimes and their drivers across the Hawaiian archipelago

PubMed Central

Jouffray, Jean-Baptiste; Nyström, Magnus; Norström, Albert V.; Williams, Ivor D.; Wedding, Lisa M.; Kittinger, John N.; Williams, Gareth J.

2015-01-01

Loss of coral reef resilience can lead to dramatic changes in benthic structure, often called regime shifts, which significantly alter ecosystem processes and functioning. In the face of global change and increasing direct human impacts, there is an urgent need to anticipate and prevent undesirable regime shifts and, conversely, to reverse shifts in already degraded reef systems. Such challenges require a better understanding of the human and natural drivers that support or undermine different reef regimes. The Hawaiian archipelago extends across a wide gradient of natural and anthropogenic conditions and provides us a unique opportunity to investigate the relationships between multiple reef regimes, their dynamics and potential drivers. We applied a combination of exploratory ordination methods and inferential statistics to one of the most comprehensive coral reef datasets available in order to detect, visualize and define potential multiple ecosystem regimes. This study demonstrates the existence of three distinct reef regimes dominated by hard corals, turf algae or macroalgae. Results from boosted regression trees show nonlinear patterns among predictors that help to explain the occurrence of these regimes, and highlight herbivore biomass as the key driver in addition to effluent, latitude and depth.

Pathogenic implications of iron accumulation in multiple sclerosis

PubMed Central

Williams, Rachel; Buchheit, Cassandra L.; Berman, Nancy E. J.; LeVine, Steven M.

2011-01-01

Iron, an essential element used for a multitude of biochemical reactions, abnormally accumulates in the central nervous system of patients with multiple sclerosis (MS). The mechanisms of abnormal iron deposition in MS are not fully understood, nor do we know whether these deposits have adverse consequences, i.e., contribute to pathogenesis. With some exceptions, excess levels of iron are represented concomitantly in multiple deep gray matter structures often with bilateral representation, while in white matter pathological iron deposits are usually located at sites of inflammation that are associated with veins. These distinct spatial patterns suggest disparate mechanisms of iron accumulation between these regions. Iron has been postulated to promote disease activity in MS by various means: 1) iron can amplify the activated state of microglia resulting in the increased production of proinflammatory mediators; 2) excess intracellular iron deposits could promote mitochondria dysfunction; and 3) improperly managed iron could catalyze the production of damaging reactive oxygen species. The pathological consequences of abnormal iron deposits may be dependent on the affected brain region and/or accumulation process. Here we review putative mechanisms of enhanced iron uptake in MS and address the likely roles of iron in the pathogenesis of this disease. PMID:22004421

Social space and cultural class divisions: the forms of capital and contemporary lifestyle differentiation.

PubMed

Flemmen, Magne; Jarness, Vegard; Rosenlund, Lennart

2018-03-01

In this article, we address whether and how contemporary social classes are marked by distinct lifestyles. We assess the model of the social space, a novel approach to class analysis pioneered by Bourdieu's Distinction. Although pivotal in Bourdieu's work, this model is too often overlooked in later research, making its contemporary relevance difficult to assess. We redress this by using the social space as a framework through which to study the cultural manifestation of class divisions in lifestyle differences in contemporary Norwegian society. Through a Multiple Correspondence Analysis (MCA) of unusually rich survey data, we reveal a structure strikingly similar to the model in Distinction, with a primary dimension of the volume of capital, and a secondary dimension of the composition of capital. While avoiding the substantialist fallacy of predefined notions of 'highbrow' and 'lowbrow' tastes, we explore how 168 lifestyle items map onto this social space. This reveals distinct classed lifestyles according to both dimensions of the social space. The lifestyles of the upper classes are distinctly demanding in terms of resources. Among those rich in economic capital, this manifests itself in a lifestyle which involves a quest for excitement, and which is bodily oriented and expensive. For their counterparts rich in cultural capital, a more ascetic and intellectually oriented lifestyle manifests itself, demanding of resources in the sense of requiring symbolic mastery, combining a taste for canonized, legitimate culture with more cosmopolitan and 'popular' items. In contrast to many studies' descriptions of the lower classes as 'disengaged' and 'inactive', we find evidence of distinct tastes on their part. Our analysis thus affirms the validity of Bourdieu's model of social class and the contention that classes tend to take the form of status groups. We challenge dominant positions in cultural stratification research, while questioning the aptness of the metaphor of the 'omnivore', as well as recent analyses of 'emerging cultural capital'. © London School of Economics and Political Science 2017.

Biology of Epstein-Barr virus during infectious mononucleosis.

PubMed

Sitki-Green, Diane L; Edwards, Rachel Hood; Covington, Mary M; Raab-Traub, Nancy

2004-02-01

Infectious mononucleosis is the clinical manifestation of primary infection with Epstein-Barr virus (EBV). We monitored primary infection during convalescence and during the establishment of persistent infection. The profiles of EBV strains in the oral cavity and in peripheral blood were determined by use of a heteroduplex tracking assay specific for the EBV gene encoding latent membrane protein 1. Multiple EBV strains were detected in most patients and persisted in and were possibly transmitted among 3 distinct compartments of infection, including the oral cavity, peripheral blood lymphocytes, and the cell-free fraction of the blood plasma. We also tracked transmission of multiple strains from an asymptomatic carrier to a patient diagnosed with primary EBV infection. These data reveal that primary EBV infection is complex, with transmission of multiple strains and clear differences in relative abundance of strains in distinct compartments.

Microcephaly, ectodermal dysplasia, multiple skeletal anomalies and distinctive facial appearance: delineation of cerebro-dermato-osseous-dysplasia.

PubMed

Castori, Marco; Pascolini, Giulia; Parisi, Valentina; Sana, Maria Elena; Novelli, Antonio; Nürnberg, Peter; Iascone, Maria; Grammatico, Paola

2015-04-01

In 1980, a novel multiple malformation syndrome has been described in a 17-year-old woman with micro- and turricephaly, intellectual disability, distinctive facial appearance, congenital atrichia, and multiple skeletal anomalies mainly affecting the limbs. Four further sporadic patients and a couple of affected sibs are also reported with a broad clinical variability. Here, we describe a 4-year-old girl strikingly resembling the original report. Phenotype comparison identified a recurrent pattern of multisystem features involving the central nervous system, and skin and bones in five sporadic patients (including ours), while the two sibs and a further sporadic case show significant phenotypic divergence. Marked clinical variability within the same entity versus syndrome splitting is discussed and the term "cerebro-dermato-osseous dysplasia" is introduced to define this condition. © 2015 Wiley Periodicals, Inc.

Ethanol-assisted gel chromatography for single-chirality separation of carbon nanotubes

NASA Astrophysics Data System (ADS)

Zeng, Xiang; Hu, Jinwen; Zhang, Xiao; Zhou, Naigen; Zhou, Weiya; Liu, Huaping; Xie, Sishen

2015-10-01

Surfactants or polymers are usually used for the liquid processing of carbon nanotubes for their structure separation. However, they are difficult to remove after separation, affecting the intrinsic properties and applications of the separated species. Here, we report an ethanol-assisted gel chromatography for the chirality separation of single-walled carbon nanotubes (SWCNTs), in which ethanol is employed to finely tune the density/coverage of sodium dodecyl sulfate (SDS) on nanotubes, and thus the interactions between SWCNTs and an allyl dextran-based gel. Incrementally increasing the ethanol content in a low-concentration SDS eluent leads to successive desorption of the different structure SWCNTs adsorbed on the gel, and to achieve multiple distinct (n, m) single-chirality species. The use of ethanol enables the working concentration of SDS to be reduced dramatically and also avoids the introduction of other surfactants or chemical reagents. More importantly, ethanol can be easily removed after separation. The ability of ethanol to tune the interactions between SWCNTs and the gel also gives a deeper insight into the separation mechanism of SWCNTs using gel chromatography.Surfactants or polymers are usually used for the liquid processing of carbon nanotubes for their structure separation. However, they are difficult to remove after separation, affecting the intrinsic properties and applications of the separated species. Here, we report an ethanol-assisted gel chromatography for the chirality separation of single-walled carbon nanotubes (SWCNTs), in which ethanol is employed to finely tune the density/coverage of sodium dodecyl sulfate (SDS) on nanotubes, and thus the interactions between SWCNTs and an allyl dextran-based gel. Incrementally increasing the ethanol content in a low-concentration SDS eluent leads to successive desorption of the different structure SWCNTs adsorbed on the gel, and to achieve multiple distinct (n, m) single-chirality species. The use of ethanol enables the working concentration of SDS to be reduced dramatically and also avoids the introduction of other surfactants or chemical reagents. More importantly, ethanol can be easily removed after separation. The ability of ethanol to tune the interactions between SWCNTs and the gel also gives a deeper insight into the separation mechanism of SWCNTs using gel chromatography. Electronic supplementary information (ESI) available: Fig. S1-S13, additional discussion and experimental details. See DOI: 10.1039/c5nr04116c

Lin28a uses distinct mechanisms of binding to RNA and affects miRNA levels positively and negatively.

PubMed

Nowak, Jakub Stanislaw; Hobor, Fruzsina; Downie Ruiz Velasco, Angela; Choudhury, Nila Roy; Heikel, Gregory; Kerr, Alastair; Ramos, Andres; Michlewski, Gracjan

2017-03-01

Lin28a inhibits the biogenesis of let-7 miRNAs by triggering the polyuridylation and degradation of their precursors by terminal uridylyltransferases TUT4/7 and 3'-5' exoribonuclease Dis3l2, respectively. Previously, we showed that Lin28a also controls the production of neuro-specific miRNA-9 via a polyuridylation-independent mechanism. Here we reveal that the sequences and structural characteristics of pre-let-7 and pre-miRNA-9 are eliciting two distinct modes of binding to Lin28a. We present evidence that Dis3l2 controls miRNA-9 production. Finally, we show that the constitutive expression of untagged Lin28a during neuronal differentiation in vitro positively and negatively affects numerous other miRNAs. Our findings shed light on the role of Lin28a in differentiating cells and on the ways in which one RNA-binding protein can perform multiple roles in the regulation of RNA processing. © 2017 Nowak et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

The role of lipids in host microbe interactions.

PubMed

Lang, Roland; Mattner, Jochen

2017-06-01

Lipids are one of the major subcellular constituents and serve as signal molecules, energy sources, metabolic precursors and structural membrane components in various organisms. The function of lipids can be modified by multiple biochemical processes such as (de-)phosphorylation or (de-)glycosylation, and the organization of fatty acids into distinct cellular pools and subcellular compartments plays a pivotal role for the morphology and function of various cell populations. Thus, lipids regulate, for example, phagosome formation and maturation within host cells and thus, are critical for the elimination of microbial pathogens. Vice versa, microbial pathogens can manipulate the lipid composition of phagosomal membranes in host cells, and thus avoid their delivery to phagolysosomes. Lipids of microbial origin belong also to the strongest and most versatile inducers of mammalian immune responses upon engagement of distinct receptors on myeloid and lymphoid cells. Furthermore, microbial lipid toxins can induce membrane injuries and cell death. Thus, we will review here selected examples for mutual host-microbe interactions within the broad and divergent universe of lipids in microbial defense, tissue injury and immune evasion.

Tissue-Specific Chromatin Modifications at a Multigene Locus Generate Asymmetric Transcriptional Interactions

PubMed Central

Yoo, Eung Jae; Cajiao, Isabela; Kim, Jeong-Seon; Kimura, Atsushi P.; Zhang, Aiwen; Cooke, Nancy E.; Liebhaber, Stephen A.

2006-01-01

Random assortment within mammalian genomes juxtaposes genes with distinct expression profiles. This organization, along with the prevalence of long-range regulatory controls, generates a potential for aberrant transcriptional interactions. The human CD79b/GH locus contains six tightly linked genes with three mutually exclusive tissue specificities and interdigitated control elements. One consequence of this compact organization is that the pituitarycell-specific transcriptional events that activate hGH-N also trigger ectopic activation of CD79b. However, the B-cell-specific events that activate CD79b do not trigger reciprocal activation of hGH-N. Here we utilized DNase I hypersensitive site mapping, chromatin immunoprecipitation, and transgenic models to explore the basis for this asymmetric relationship. The results reveal tissue-specific patterns of chromatin structures and transcriptional controls at the CD79b/GH locus in B cells distinct from those in the pituitary gland and placenta. These three unique transcriptional environments suggest a set of corresponding gene expression pathways and transcriptional interactions that are likely to be found juxtaposed at multiple sites within the eukaryotic genome. PMID:16847312

Combining a Toggle Switch and a Repressilator within the AC-DC Circuit Generates Distinct Dynamical Behaviors.

PubMed

Perez-Carrasco, Ruben; Barnes, Chris P; Schaerli, Yolanda; Isalan, Mark; Briscoe, James; Page, Karen M

2018-04-25

Although the structure of a genetically encoded regulatory circuit is an important determinant of its function, the relationship between circuit topology and the dynamical behaviors it can exhibit is not well understood. Here, we explore the range of behaviors available to the AC-DC circuit. This circuit consists of three genes connected as a combination of a toggle switch and a repressilator. Using dynamical systems theory, we show that the AC-DC circuit exhibits both oscillations and bistability within the same region of parameter space; this generates emergent behaviors not available to either the toggle switch or the repressilator alone. The AC-DC circuit can switch on oscillations via two distinct mechanisms, one of which induces coherence into ensembles of oscillators. In addition, we show that in the presence of noise, the AC-DC circuit can behave as an excitable system capable of spatial signal propagation or coherence resonance. Together, these results demonstrate how combinations of simple motifs can exhibit multiple complex behaviors. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Pathways to fraction learning: Numerical abilities mediate the relation between early cognitive competencies and later fraction knowledge.

PubMed

Ye, Ai; Resnick, Ilyse; Hansen, Nicole; Rodrigues, Jessica; Rinne, Luke; Jordan, Nancy C

2016-12-01

The current study investigated the mediating role of number-related skills in the developmental relationship between early cognitive competencies and later fraction knowledge using structural equation modeling. Fifth-grade numerical skills (i.e., whole number line estimation, non-symbolic proportional reasoning, multiplication, and long division skills) mapped onto two distinct factors: magnitude reasoning and calculation. Controlling for participants' (N=536) demographic characteristics, these two factors fully mediated relationships between third-grade general cognitive competencies (attentive behavior, verbal and nonverbal intellectual abilities, and working memory) and sixth-grade fraction knowledge (concepts and procedures combined). However, specific developmental pathways differed by type of fraction knowledge. Magnitude reasoning ability fully mediated paths from all four cognitive competencies to knowledge of fraction concepts, whereas calculation ability fully mediated paths from attentive behavior and verbal ability to knowledge of fraction procedures (all with medium to large effect sizes). These findings suggest that there are partly overlapping, yet distinct, developmental pathways from cognitive competencies to general fraction knowledge, fraction concepts, and fraction procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Tuskan, Gerald A; Tschaplinski, Timothy J; Chen, Jay

Genetic determination of gender is a fundamental developmental and evolutionary process in plants. Although it appears that dioecy in Populus is partially genetically controlled, the precise gender-determining systems remain unclear. The recently-released second draft assembly and annotated gene set of the Populus genome provided an opportunity to re-visit this topic. We hypothesized that over evolutionary time, selective pressure has reformed the genome structure and gene composition in the peritelomeric region of the chromosome XIX which has resulted in a distinctive genome structure and cluster of genes contributing to gender determination in Populus. Multiple lines of evidence support this working hypothesis.more » First, the peritelomeric region of the chromosome XIX contains significantly fewer single nucleotide polymorphisms than the rest of Populus genome and has a distinct evolutionary history. Second, the peritelomeric end of chromosome XIX contains the largest cluster of the nucleotide-binding site-leucine-rich repeat (NBS-LRR) class of disease resistances genes in the entire Populus genome. Third, there is a high occurrence of small microRNAs on chromosome XIX coincident to the region containing the putative gender-determining locus and the major cluster of NBS-LRR genes. Further, by analyzing the metabolomic profiles of floral bud in male and female Populus trees using a gas chromatography-mass spectrometry, we found there are gender-specific accumulations of phenolic glycosides. Taken together, these findings provide new insights into the genetic control of gender determination in Populus.« less

Mutations in the Arabidopsis Peroxisomal ABC Transporter COMATOSE Allow Differentiation between Multiple Functions In Planta: Insights from an Allelic Series

PubMed Central

Dietrich, Daniela; Schmuths, Heike; Lousa, Carine De Marcos; Baldwin, Jocelyn M.; Baldwin, Stephen A.; Baker, Alison; Holdsworth, Michael J.

2009-01-01

COMATOSE (CTS), the Arabidopsis homologue of human Adrenoleukodystrophy protein (ALDP), is required for import of substrates for peroxisomal β-oxidation. A new allelic series and a homology model based on the bacterial ABC transporter, Sav1866, provide novel insights into structure-function relations of ABC subfamily D proteins. In contrast to ALDP, where the majority of mutations result in protein absence from the peroxisomal membrane, all CTS mutants produced stable protein. Mutation of conserved residues in the Walker A and B motifs in CTS nucleotide-binding domain (NBD) 1 resulted in a null phenotype but had little effect in NBD2, indicating that the NBDs are functionally distinct in vivo. Two alleles containing mutations in NBD1 outside the Walker motifs (E617K and C631Y) exhibited resistance to auxin precursors 2,4-dichlorophenoxybutyric acid (2,4-DB) and indole butyric acid (IBA) but were wild type in all other tests. The homology model predicted that the transmission interfaces are domain-swapped in CTS, and the differential effects of mutations in the conserved “EAA motif” of coupling helix 2 supported this prediction, consistent with distinct roles for each NBD. Our findings demonstrate that CTS functions can be separated by mutagenesis and the structural model provides a framework for interpretation of phenotypic data. PMID:19019987

Molecular complexity of successive bacterial epidemics deconvoluted by comparative pathogenomics.

PubMed

Beres, Stephen B; Carroll, Ronan K; Shea, Patrick R; Sitkiewicz, Izabela; Martinez-Gutierrez, Juan Carlos; Low, Donald E; McGeer, Allison; Willey, Barbara M; Green, Karen; Tyrrell, Gregory J; Goldman, Thomas D; Feldgarden, Michael; Birren, Bruce W; Fofanov, Yuriy; Boos, John; Wheaton, William D; Honisch, Christiane; Musser, James M

2010-03-02

Understanding the fine-structure molecular architecture of bacterial epidemics has been a long-sought goal of infectious disease research. We used short-read-length DNA sequencing coupled with mass spectroscopy analysis of SNPs to study the molecular pathogenomics of three successive epidemics of invasive infections involving 344 serotype M3 group A Streptococcus in Ontario, Canada. Sequencing the genome of 95 strains from the three epidemics, coupled with analysis of 280 biallelic SNPs in all 344 strains, revealed an unexpectedly complex population structure composed of a dynamic mixture of distinct clonally related complexes. We discovered that each epidemic is dominated by micro- and macrobursts of multiple emergent clones, some with distinct strain genotype-patient phenotype relationships. On average, strains were differentiated from one another by only 49 SNPs and 11 insertion-deletion events (indels) in the core genome. Ten percent of SNPs are strain specific; that is, each strain has a unique genome sequence. We identified nonrandom temporal-spatial patterns of strain distribution within and between the epidemic peaks. The extensive full-genome data permitted us to identify genes with significantly increased rates of nonsynonymous (amino acid-altering) nucleotide polymorphisms, thereby providing clues about selective forces operative in the host. Comparative expression microarray analysis revealed that closely related strains differentiated by seemingly modest genetic changes can have significantly divergent transcriptomes. We conclude that enhanced understanding of bacterial epidemics requires a deep-sequencing, geographically centric, comparative pathogenomics strategy.

Numerical Simulations of Silverpit Crater Collapse

NASA Technical Reports Server (NTRS)

Collins, G. S.; Ivanov, B. A.; Turtle, E. P.; Melosh, H. J.

2003-01-01

The Silverpit crater is a recently discovered, 60-65 Myr old complex crater, which lies buried beneath the North Sea, about 150 km east of Britain. High-resolution images of Silverpit's subsurface structure, provided by three-dimensional seismic reflection data, reveal an inner-crater morphology similar to that expected for a 5-8 km diameter terrestrial crater. The crater walls show evidence of terrace-style slumping and there is a distinct central uplift, which may have produced a central peak in the pristine crater morphology. However, Silverpit is not a typical 5-km diameter terrestrial crater, because it exhibits multiple, concentric rings outside the main cavity. External concentric rings are normally associated with much larger impact structures, for example Chicxulub on Earth, or Orientale on the Moon. Furthermore, external rings associated with large impacts on the terrestrial planets and moons are widely-spaced, predominantly inwardly-facing, asymmetric scarps. However, the seismic data show that the external rings at Silverpit represent closely-spaced, concentric faultbound graben, with both inwardly and outwardly facing fault-scarps. This type of multi-ring structure directly analogous to the Valhalla-type multi-ring basins found on the icy satellites. Thus, the presence and style of the multiple rings at Silverpit is surprising given both the size of the crater and its planetary setting. A further curiosity of the Silverpit structure is that the external concentric rings appear to be extensional features on the West side of the crater and compressional features on the East side. The crater also lies in a local depression, thought to be created by postimpact movement of a salt layer buried beneath the crater.

Diversity of Staphylococcus pseudintermedius in carriage sites and skin lesions of dogs with superficial bacterial folliculitis: potential implications for diagnostic testing and therapy.

PubMed

Larsen, Rikke Friis; Boysen, Lene; Jessen, Lisbeth Rem; Guardabassi, Luca; Damborg, Peter

2018-05-21

Staphylococcus pseudintermedius is genotypically diverse within the canine population and multiple strains may colonize individual dogs at any given time. If multiple strains with distinct antimicrobial resistance profiles are present in superficial bacterial folliculitis (SBF), sampling a single skin lesion for culture and antimicrobial susceptibility testing (AST) might be inadequate to select effective therapy. To investigate S. pseudintermedius diversity in carriage sites and lesions of dogs with SBF. Fourteen dogs with SBF. Staphylococcus pseudintermedius isolates obtained from perineum, gingiva and four to six skin lesions per dog were subjected to pulsed-field gel electrophoresis (PFGE) and AST to assess diversity between lesions. For two dogs, 14-16 isolates per lesion were included in the analysis to assess diversity within lesions. Analysis of one isolate per lesion revealed one to four strains displaying unique PFGE profiles, and up to three unique antimicrobial resistance (AMR) profiles for each dog. Multiple pustules from the same dog always harboured the same strain, whereas papules, crusts and collarettes did not. Up to four strains with distinct AMR profiles were isolated from the same lesion in two dogs. In 12 dogs, at least one carriage site strain also was represented in lesions. Lesions of SBF may harbour multiple S. pseudintermedius strains with distinct antimicrobial resistance profiles. Pustules are the best target for bacterial culture. It remains unclear whether isolation of different strains from other lesion types is a consequence of contamination or co-infection by multiple strains. © 2018 ESVD and ACVD.

The intrinsically disordered C-terminal domain of the measles virus nucleoprotein interacts with the C-terminal domain of the phosphoprotein via two distinct sites and remains predominantly unfolded

PubMed Central

Bourhis, Jean-Marie; Receveur-Bréchot, Véronique; Oglesbee, Michael; Zhang, Xinsheng; Buccellato, Matthew; Darbon, Hervé; Canard, Bruno; Finet, Stéphanie; Longhi, Sonia

2005-01-01

Measles virus is a negative-sense, single-stranded RNA virus within theMononegavirales order,which includes several human pathogens, including rabies, Ebola, Nipah, and Hendra viruses. Themeasles virus nucleoprotein consists of a structured N-terminal domain, and of an intrinsically disordered C-terminal domain, NTAIL (aa 401–525), which undergoes induced folding in the presence of the C-terminal domain (XD, aa 459–507) of the viral phosphoprotein. With in NTAIL, an α-helical molecular recognition element (α-MoRE, aa 488–499) involved in binding to P and in induced folding was identified and then observed in the crystal structure of XD. Using small-angle X-ray scattering, we have derived a low-resolution structural model of the complex between XD and NTAIL, which shows that most of NTAIL remains disordered in the complex despite P-induced folding within the α-MoRE. The model consists of an extended shape accommodating the multiple conformations adopted by the disordered N-terminal region of NTAIL, and of a bulky globular region, corresponding to XD and to the C terminus of NTAIL (aa 486–525). Using surface plasmon resonance, circular dichroism, fluorescence spectroscopy, and heteronuclear magnetic resonance, we show that NTAIL has an additional site (aa 517–525) involved in binding to XD but not in the unstructured-to-structured transition. This work provides evidence that intrinsically disordered domains can establish complex interactions with their partners, and can contact them through multiple sites that do not all necessarily gain regular secondary structure. PMID:16046624

Disrupted topological organization of structural networks revealed by probabilistic diffusion tractography in Tourette syndrome children.

PubMed

Wen, Hongwei; Liu, Yue; Rekik, Islem; Wang, Shengpei; Zhang, Jishui; Zhang, Yue; Peng, Yun; He, Huiguang

2017-08-01

Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder. Although previous TS studies revealed structural abnormalities in distinct corticobasal ganglia circuits, the topological alterations of the whole-brain white matter (WM) structural networks remain poorly understood. Here, we used diffusion MRI probabilistic tractography and graph theoretical analysis to investigate the topological organization of WM networks in 44 drug-naive TS children and 41 age- and gender-matched healthy children. The WM networks were constructed by estimating inter-regional connectivity probability and the topological properties were characterized using graph theory. We found that both TS and control groups showed an efficient small-world organization in WM networks. However, compared to controls, TS children exhibited decreased global and local efficiency, increased shortest path length and small worldness, indicating a disrupted balance between local specialization and global integration in structural networks. Although both TS and control groups showed highly similar hub distributions, TS children exhibited significant decreased nodal efficiency, mainly distributed in the default mode, language, visual, and sensorimotor systems. Furthermore, two separate networks showing significantly decreased connectivity in TS group were identified using network-based statistical (NBS) analysis, primarily composed of the parieto-occipital cortex, precuneus, and paracentral lobule. Importantly, we combined support vector machine and multiple kernel learning frameworks to fuse multiple levels of network topological features for classification of individuals, achieving high accuracy of 86.47%. Together, our study revealed the disrupted topological organization of structural networks related to pathophysiology of TS, and the discriminative topological features for classification are potential quantitative neuroimaging biomarkers for clinical TS diagnosis. Hum Brain Mapp 38:3988-4008, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Multiple competing interactions and reentrant ferrimagnetism in Tb 0.8Nd 0.2Mn 6Ge 6

NASA Astrophysics Data System (ADS)

Schobinger-Papamantellos, P.; André, G.; Rodríguez-Carvajal, J.; Duong, N. P.; Buschow, K. H. J.

2001-06-01

The magnetic ordering of the hexagonal compound Tb 0.8Nd 0.2Mn 6Ge 6 has been studied by neutron diffraction and magnetic measurements in the temperature range 1.5-800 K. This compound was found to undergo consecutive magnetic transitions with temperature. The magnetic phase diagram comprises four distinct regions and requires the wave vectors: q1=(0, 0, qz) and q2=0 for its description. The low temperature range (LT): 1.5 K< T< T1=85 K, is characterised by a triple ferrimagnetic conical (spiral) structure with qz=0.128 r.l.u and a net moment along the c direction ( q2=0). The intermediate temperature range displays two transitions: At T1=85 K the conical structure transforms to a simple triple (flat) spiral persisting in range (ITa) 85 K< T< T2≈340 K, with a small thermal variation of the wave vector. Above T2 in range (ITb) T2< T< TS≈390 K the destabilised spiral transforms to a FAN-like structure with a fast decrease of the wave vector length towards zero while a ferrimagnetic planar structure ( q2=0) develops at the cost of the spiral. The planar ferrimagnetic magnetic structure ( q2=0) dominates the high temperature range (HT) 390 K< T< Tc=450 K. The onset of re-entrant ferrimagnetism reflects the interplay of multiple competing inter- and intra- sublattice interactions of the three types of magnetic ions with different crystal field anisotropies. The Nd and Tb sublattices are coupled antiferromagnetically while the Tb-Mn and Nd-Mn interactions are negative and positive, respectively.

Geometric Patterns for Neighboring Bases Near the Stacked State in Nucleic Acid Strands.

PubMed

Sedova, Ada; Banavali, Nilesh K

2017-03-14

Structural variation in base stacking has been analyzed frequently in isolated double helical contexts for nucleic acids, but not as often in nonhelical geometries or in complex biomolecular environments. In this study, conformations of two neighboring bases near their stacked state in any environment are comprehensively characterized for single-strand dinucleotide (SSD) nucleic acid crystal structure conformations. An ensemble clustering method is used to identify a reduced set of representative stacking geometries based on pairwise distances between select atoms in consecutive bases, with multiple separable conformational clusters obtained for categories divided by nucleic acid type (DNA/RNA), SSD sequence, stacking face orientation, and the presence or absence of a protein environment. For both DNA and RNA, SSD conformations are observed that are either close to the A-form, or close to the B-form, or intermediate between the two forms, or further away from either form, illustrating the local structural heterogeneity near the stacked state. Among this large variety of distinct conformations, several common stacking patterns are observed between DNA and RNA, and between nucleic acids in isolation or in complex with proteins, suggesting that these might be stable stacking orientations. Noncanonical face/face orientations of the two bases are also observed for neighboring bases in the same strand, but their frequency is much lower, with multiple SSD sequences across categories showing no occurrences of such unusual stacked conformations. The resulting reduced set of stacking geometries is directly useful for stacking-energy comparisons between empirical force fields, prediction of plausible localized variations in single-strand structures near their canonical states, and identification of analogous stacking patterns in newly solved nucleic acid containing structures.

Amobarbital treatment of multiple personality. Use of structured video tape interviews as a basis for intensive psychotherapy.

PubMed

Hall, R C; LeCann, A F; Schoolar, J C

1978-09-01

The case of a 30-year-old woman with five distinct personalities is presented. The patient was treated, using a system of structured video taped sodium amobarbital interviews, in which areas to be explored were developed in psychotherapy. Tapes were played for the patient after each session. The taped material was used as the basis for psychotherapeutic investigation. The patient evidenced many of the features previously reported in cases of multiple personality, specifically: being the product of an unwanted pregnancy in a repressively rigid family; emotional distancing by one parent; strong sibling rivalry with an adopted sib; family history of mental illness; a traumatic first sexual experience (rape); a marriage to a maladjusted individual in an attempt to escape the parental home; a high internalized standard of performance and an inability to display anger or negative feelings toward the parents. In the course of treatment, the patient's personalties fused and she was able to accept each component as part of herself. No further fragmentation has occurred during the year following discharge. The therapy technique minimized dependency, and the possiblity of addiction to amobarbital interviews permitted more active patient therapy involvement, and set clear-cut goals and expectations for improvement before further amobarbital interviews could be conducted.

Dissecting the genetic structure and admixture of four geographical Malay populations

PubMed Central

Deng, Lian; Hoh, Boon-Peng; Lu, Dongsheng; Saw, Woei-Yuh; Twee-Hee Ong, Rick; Kasturiratne, Anuradhani; Janaka de Silva, H.; Zilfalil, Bin Alwi; Kato, Norihiro; Wickremasinghe, Ananda R.; Teo, Yik-Ying; Xu, Shuhua

2015-01-01

The Malay people are an important ethnic composition in Southeast Asia, but their genetic make-up and population structure remain poorly studied. Here we conducted a genome-wide study of four geographical Malay populations: Peninsular Malaysian Malay (PMM), Singaporean Malay (SGM), Indonesian Malay (IDM) and Sri Lankan Malay (SLM). All the four Malay populations showed substantial admixture with multiple ancestries. We identified four major ancestral components in Malay populations: Austronesian (17%–62%), Proto-Malay (15%–31%), East Asian (4%–16%) and South Asian (3%–34%). Approximately 34% of the genetic makeup of SLM is of South Asian ancestry, resulting in its distinct genetic pattern compared with the other three Malay populations. Besides, substantial differentiation was observed between the Malay populations from the north and the south, and between those from the west and the east. In summary, this study revealed that the genetic identity of the Malays comprises a mixed entity of multiple ancestries represented by Austronesian, Proto-Malay, East Asian and South Asian, with most of the admixture events estimated to have occurred 175 to 1,500 years ago, which in turn suggests that geographical isolation and independent admixture have significantly shaped the genetic architectures and the diversity of the Malay populations. PMID:26395220

Marginal Structural Cox Models for Estimating the Association Between β-Interferon Exposure and Disease Progression in a Multiple Sclerosis Cohort

PubMed Central

Karim, Mohammad Ehsanul; Gustafson, Paul; Petkau, John; Zhao, Yinshan; Shirani, Afsaneh; Kingwell, Elaine; Evans, Charity; van der Kop, Mia; Oger, Joel; Tremlett, Helen

2014-01-01

Longitudinal observational data are required to assess the association between exposure to β-interferon medications and disease progression among relapsing-remitting multiple sclerosis (MS) patients in the “real-world” clinical practice setting. Marginal structural Cox models (MSCMs) can provide distinct advantages over traditional approaches by allowing adjustment for time-varying confounders such as MS relapses, as well as baseline characteristics, through the use of inverse probability weighting. We assessed the suitability of MSCMs to analyze data from a large cohort of 1,697 relapsing-remitting MS patients in British Columbia, Canada (1995–2008). In the context of this observational study, which spanned more than a decade and involved patients with a chronic yet fluctuating disease, the recently proposed “normalized stabilized” weights were found to be the most appropriate choice of weights. Using this model, no association between β-interferon exposure and the hazard of disability progression was found (hazard ratio = 1.36, 95% confidence interval: 0.95, 1.94). For sensitivity analyses, truncated normalized unstabilized weights were used in additional MSCMs and to construct inverse probability weight-adjusted survival curves; the findings did not change. Additionally, qualitatively similar conclusions from approximation approaches to the weighted Cox model (i.e., MSCM) extend confidence in the findings. PMID:24939980

The contrasting nature of woody plant species in different neotropical forest biomes reflects differences in ecological stability.

PubMed

Pennington, R Toby; Lavin, Matt

2016-04-01

A fundamental premise of this review is that distinctive phylogenetic and biogeographic patterns in clades endemic to different major biomes illuminate the evolutionary process. In seasonally dry tropical forests (SDTFs), phylogenies are geographically structured and multiple individuals representing single species coalesce. This pattern of monophyletic species, coupled with their old species stem ages, is indicative of maintenance of small effective population sizes over evolutionary timescales, which suggests that SDTF is difficult to immigrate into because of persistent resident lineages adapted to a stable, seasonally dry ecology. By contrast, lack of coalescence in conspecific accessions of abundant and often widespread species is more frequent in rain forests and is likely to reflect large effective population sizes maintained over huge areas by effective seed and pollen flow. Species nonmonophyly, young species stem ages and lack of geographical structure in rain forest phylogenies may reflect more widespread disturbance by drought and landscape evolution causing resident mortality that opens up greater opportunities for immigration and speciation. We recommend full species sampling and inclusion of multiple accessions representing individual species in phylogenies to highlight nonmonophyletic species, which we predict will be frequent in rain forest and savanna, and which represent excellent case studies of incipient speciation. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

A survey. Financial accounting and internal control functions pursued by hospital boards.

PubMed

Gavin, T A

1984-09-01

Justification for a board committee's existence is its ability to devote time to issues judged to be important by the full board. This seems to have happened. Multiple committees pursue more functions than the other committee structures. Boards lacking an FA/IC committee pursue significantly fewer functions than their counterparts with committees. Substantial respondent agreement exists on those functions most and least frequently pursued, those perceived to be most and least important, and those perceived to be most and least effectively undertaken. Distinctions between committee structures and the full board, noted in the previous paragraph, hold true with respect to the importance of functions. All board structures identified reviewing the budget and comparing it to actual results as important. Committee structures are generally more inclined to address functions related to the work of the independent auditor and the effectiveness of the hospital's system and controls than are full board structures. Functions related to the internal auditor are pursued least frequently by all FA/IC board structures. The following suggestions are made to help boards pay adequate attention to and obtain objective information about the financial affairs of their hospitals. Those boards that do not have some form of an FA/IC committee should consider starting one. Evidence shows chief financial officers have been a moving force in establishing and strengthening such committees. Boards having a joint or single committee structure should consider upgrading their structure to either a single committee or multiple committees respectively. The complexity of the healthcare environment requires that more FA/IC functions be addressed by the board. The board or its FA/IC committee(s) should meet with their independent CPA's, fiscal intermediary auditors, and internal auditors. Where the hospital lacks an internal audit function a study should be undertaken to determine the feasibility of initiating such a function. In most cases, the benefits derived from an independent, properly staffed internal audit function far exceed the cost of such a function.

Crustal structure of Central Sicily

NASA Astrophysics Data System (ADS)

Giustiniani, Michela; Tinivella, Umberta; Nicolich, Rinaldo

2018-01-01

We processed crustal seismic profile SIRIPRO, acquired across Central Sicily. To improve the seismic image we utilized the wave equation datuming technique, a process of upward or downward continuation of the wave-field between two arbitrarily shaped surfaces. Wave equation datuming was applied to move shots and receivers to a given datum plane, removing time shifts related to topography and to near-surface velocity variations. The datuming procedure largely contributed to attenuate ground roll, enhance higher frequencies, increase resolution and improve the signal/noise ratio. Processed data allow recognizing geometries of crust structures differentiating seismic facies and offering a direct image of ongoing tectonic setting within variable lithologies characterizing the crust of Central Sicily. Migrated sections underline distinctive features of Hyblean Plateau foreland and above all a crustal thinning towards the Caltanissetta trough, to the contact with a likely deep Permo-Triassic rifted basin or rather a zone of a continent to oceanic transition. Inhomogeneity and fragmentation of Sicily crust, with a distinct separation of Central Sicily basin from western and eastern blocks, appear to have guided the tectonic transport inside the Caltanissetta crustal scale syncline and the accumulation of allochthonous terrains with south and north-verging thrusts. Major tectonic stack operated on the construction of a wide anticline of the Maghrebian chain in northern Sicily. Sequential south-verging imbrications of deep elements forming the anticline core denote a crust wedge indenting foreland structures. Deformation processes involved multiple detachment planes down to decoupling levels located near crust/mantle transition, supporting a presence of high-density lenses beneath the chain, interrelated to a southwards push of Tyrrhenian mantle and asthenosphere.

Molecular design of boronic acid-functionalized squarylium cyanine dyes for multiple discriminant analysis of sialic acid in biological samples: selectivity toward monosaccharides controlled by different alkyl side chain lengths.

PubMed

Ouchi, Kazuki; Colyer, Christa L; Sebaiy, Mahmoud; Zhou, Jin; Maeda, Takeshi; Nakazumi, Hiroyuki; Shibukawa, Masami; Saito, Shingo

2015-02-03

We designed a new series of boronic acid-functionalized squarylium cyanine dyes (SQ-BA) with different lengths of alkyl chain residues, suitable for multiple discriminant analysis (MDA) of sialic acid (Neu5Ac) in biological samples. The SQ-BA dyes form aggregates based on hydrophobic interactions, which result in quenched fluorescence in aqueous solutions. When the boronic acid binds with saccharides, the fluorescence intensity increases as a result of dissociation to the emissive monomeric complex. We inferred that different dye aggregate structures (H-aggregates and J-aggregates) were induced depending on the alkyl chain length, so that monosaccharides would be recognized in different ways (especially, multipoint interaction with J-aggregates). A distinctive emission enhancement of SQ-BA dyes with shorter-alkyl-chains in the presence of Neu5Ac was observed (2.4-fold fluorescence enhancement; with formation constant 10(1.7) M(-1)), with no such enhancement for SQ-BA dyes with longer-alkyl-chain. In addition, various enhancement factors for other monosaccharides were observed depending on the alkyl chain length. Detailed thermodynamic and NMR studies of the SQ-BA complexes revealed the unique recognition mechanism: the dye aggregate with a shorter-alkyl-chain causes the slipped parallel structure and forms a stable 2:1 complex with Neu5Ac, as distinct from longer-alkyl-chain dyes, which form a 1:1 monomeric complex. MDA using the four SQ-BA dyes was performed for human urine samples, resulting in the successful discrimination between normal and abnormal Neu5Ac levels characteristic of disease. Thus, we successfully controlled various responses to similar monosaccharides with a novel approach that chemically modified not the boronic acid moiety itself but the length of the alkyl chain residue attached to the dye in order to generate specificity.

Multimodal fluorescence microscopy of prion strain specific PrP deposits stained by thiophene-based amyloid ligands.

PubMed

Magnusson, Karin; Simon, Rozalyn; Sjölander, Daniel; Sigurdson, Christina J; Hammarström, Per; Nilsson, K Peter R

2014-01-01

The disease-associated prion protein (PrP) forms aggregates which vary in structural conformation yet share an identical primary sequence. These variations in PrP conformation are believed to manifest in prion strains exhibiting distinctly different periods of disease incubation as well as regionally specific aggregate deposition within the brain. The anionic luminescent conjugated polythiophene (LCP), polythiophene acetic acid (PTAA) has previously been used to distinguish PrP deposits associated with distinct mouse adapted strains via distinct fluorescence emission profiles from the dye. Here, we employed PTAA and 3 structurally related chemically defined luminescent conjugated oligothiophenes (LCOs) to stain brain tissue sections from mice inoculated with 2 distinct prion strains. Our results showed that in addition to emission spectra, excitation, and fluorescence lifetime imaging microscopy (FLIM) can fruitfully be assessed for optical distinction of PrP deposits associated with distinct prion strains. Our findings support the theory that alterations in LCP/LCO fluorescence are due to distinct conformational restriction of the thiophene backbone upon interaction with PrP aggregates associated with distinct prion strains. We foresee that LCP and LCO staining in combination with multimodal fluorescence microscopy might aid in detecting structural differences among discrete protein aggregates and in linking protein conformational features with disease phenotypes for a variety of neurodegenerative proteinopathies.

Multimodal fluorescence microscopy of prion strain specific PrP deposits stained by thiophene-based amyloid ligands

PubMed Central

Magnusson, Karin; Simon, Rozalyn; Sjölander, Daniel; Sigurdson, Christina J; Hammarström, Per; Nilsson, K Peter R

2014-01-01

The disease-associated prion protein (PrP) forms aggregates which vary in structural conformation yet share an identical primary sequence. These variations in PrP conformation are believed to manifest in prion strains exhibiting distinctly different periods of disease incubation as well as regionally specific aggregate deposition within the brain. The anionic luminescent conjugated polythiophene (LCP), polythiophene acetic acid (PTAA) has previously been used to distinguish PrP deposits associated with distinct mouse adapted strains via distinct fluorescence emission profiles from the dye. Here, we employed PTAA and 3 structurally related chemically defined luminescent conjugated oligothiophenes (LCOs) to stain brain tissue sections from mice inoculated with 2 distinct prion strains. Our results showed that in addition to emission spectra, excitation, and fluorescence lifetime imaging microscopy (FLIM) can fruitfully be assessed for optical distinction of PrP deposits associated with distinct prion strains. Our findings support the theory that alterations in LCP/LCO fluorescence are due to distinct conformational restriction of the thiophene backbone upon interaction with PrP aggregates associated with distinct prion strains. We foresee that LCP and LCO staining in combination with multimodal fluorescence microscopy might aid in detecting structural differences among discrete protein aggregates and in linking protein conformational features with disease phenotypes for a variety of neurodegenerative proteinopathies. PMID:25495506

Increased dysbindin-1B isoform expression in schizophrenia and its propensity in aggresome formation

PubMed Central

Xu, Yiliang; Sun, Yuhui; Ye, Haihong; Zhu, Li; Liu, Jianghong; Wu, Xiaofeng; Wang, Le; He, Tingting; Shen, Yan; Wu, Jane Y; Xu, Qi

2015-01-01

Genetic variations in the human dysbindin-1 gene (DTNBP1) have been associated with schizophrenia. As a result of alternative splicing, the human DTNBP1 gene generates at least three distinct protein isoforms, dysbindin-1A, -1B and -1C. Significant effort has focused on dysbindin-1A, an important player in multiple steps of neurodevelopment. However, the other isoforms, dysbindin-1B and dysbindin-1C have not been well characterized. Nor have been associated with human diseases. Here we report an increase in expression of DTNBP1b mRNA in patients with paranoid schizophrenia as compared with healthy controls. A single-nucleotide polymorphism located in intron 9, rs117610176, has been identified and associated with paranoid schizophrenia, and its C allele leads to an increase of DTNBP1b mRNA splicing. Our data show that different dysbindin splicing isoforms exhibit distinct subcellular distribution, suggesting their distinct functional activities. Dysbindin-1B forms aggresomes at the perinuclear region, whereas dysbindin-1A and -1C proteins exhibit diffused patterns in the cytoplasm. Dysbindin-1A interacts with dysbindin-1B, getting recruited to the aggresome structure when co-expressed with dysbindin-1B. Moreover, cortical neurons over-expressing dysbindin-1B show reduction in neurite outgrowth, suggesting that dysbindin-1B may interfere with dysbindin-1A function in a dominant-negative manner. Taken together, our study uncovers a previously unknown association of DTNBP1b expression with schizophrenia in addition to its distinct biochemical and functional properties. PMID:27462430

Your Divided Attention, Please! The Maintenance of Multiple Attentional Control Sets over Distinct Regions in Space

ERIC Educational Resources Information Center

Adamo, Maha; Pun, Carson; Pratt, Jay; Ferber, Susanne

2008-01-01

When non-informative peripheral cues precede a target defined by a specific feature, cues that share the critical feature will capture attention while cues that do not will be effectively ignored. We tested whether different attentional control sets can be simultaneously maintained over distinct regions of space. Participants were instructed to…

On the formation modes in vortex interaction for multiple co-axial co-rotating vortex rings

NASA Astrophysics Data System (ADS)

Qin, Suyang; Liu, Hong; Xiang, Yang

2018-01-01

Interaction among multiple vortices is of particular importance to biological locomotion. It plays an essential role in the force and energy capture. This study examines the motion and dynamics of multiple co-axial co-rotating vortex rings. The vortex rings, which have the same formation time, are successively generated in a piston-cylinder apparatus by accurately controlling the interval time. The flow fields are visualized by the finite-time Lyapunov exponent and then repelling Lagrangian coherent structures (r-LCSs) are determined. Two types of vortex interactions ("strong" and "weak") are defined by investigating the r-LCSs: a strong interaction is indicated by connected r-LCSs showing a channel for fluid transport (termed as a "flux window"); a weak interaction is indicated by disconnected r-LCSs between the vortex rings. For strong interaction, leapfrogging and merger of vortex rings can happen in the later stage of the evolution process; however, the rings are separated for weak interaction. Two distinct formation modes, the formation enhancement mode (FEM) and formation restraint mode (FRM), refer to the effect of one or multiple vortex ring(s) on the initial circulation of the subsequently formed vortex ring. In the FEM, the circulation of a vortex ring is larger than that of an isolated (without interaction) vortex ring. On the other hand, the situation is opposite in the FRM. A dimensionless number reflecting the interaction mechanism, "structure stretching number" S*, is proposed, which evaluates the induced effect of the wake vortices on the formation of a vortex ring. A limiting S* (SL*=(2 ±0.4 ) ×1 0-4) is the bifurcation point of the two formation modes. The augmentation of circulation reaches up to 10% for the FEM when S*SL*), the circulation decreases for at most 20%. The newly defined formation modes and number could shed light on the understanding of the dynamics of multiple vortex ring flows.

Synergies and Distinctions between Computational Disciplines in Biomedical Research: Perspective from the Clinical and Translational Science Award Programs

PubMed Central

Bernstam, Elmer V.; Hersh, William R.; Johnson, Stephen B.; Chute, Christopher G.; Nguyen, Hien; Sim, Ida; Nahm, Meredith; Weiner, Mark; Miller, Perry; DiLaura, Robert P.; Overcash, Marc; Lehmann, Harold P.; Eichmann, David; Athey, Brian D.; Scheuermann, Richard H.; Anderson, Nick; Starren, Justin B.; Harris, Paul A.; Smith, Jack W.; Barbour, Ed; Silverstein, Jonathan C.; Krusch, David A.; Nagarajan, Rakesh; Becich, Michael J.

2010-01-01

Clinical and translational research increasingly requires computation. Projects may involve multiple computationally-oriented groups including information technology (IT) professionals, computer scientists and biomedical informaticians. However, many biomedical researchers are not aware of the distinctions among these complementary groups, leading to confusion, delays and sub-optimal results. Although written from the perspective of clinical and translational science award (CTSA) programs within academic medical centers, the paper addresses issues that extend beyond clinical and translational research. The authors describe the complementary but distinct roles of operational IT, research IT, computer science and biomedical informatics using a clinical data warehouse as a running example. In general, IT professionals focus on technology. The authors distinguish between two types of IT groups within academic medical centers: central or administrative IT (supporting the administrative computing needs of large organizations) and research IT (supporting the computing needs of researchers). Computer scientists focus on general issues of computation such as designing faster computers or more efficient algorithms, rather than specific applications. In contrast, informaticians are concerned with data, information and knowledge. Biomedical informaticians draw on a variety of tools, including but not limited to computers, to solve information problems in health care and biomedicine. The paper concludes with recommendations regarding administrative structures that can help to maximize the benefit of computation to biomedical research within academic health centers. PMID:19550198

An Atomistic View of Amyloidogenic Self-assembly: Structure and Dynamics of Heterogeneous Conformational States in the Pre-nucleation Phase

PubMed Central

Matthes, Dirk; Gapsys, Vytautas; Brennecke, Julian T.; de Groot, Bert L.

2016-01-01

The formation of well-defined filamentous amyloid structures involves a polydisperse collection of oligomeric states for which relatively little is known in terms of structural organization. Here we use extensive, unbiased explicit solvent molecular dynamics (MD) simulations to investigate the structural and dynamical features of oligomeric aggregates formed by a number of highly amyloidogenic peptides at atomistic resolution on the μs time scale. A consensus approach has been adopted to analyse the simulations in multiple force fields, yielding an in-depth characterization of pre-fibrillar oligomers and their global and local structure properties. A collision cross section analysis revealed structurally heterogeneous aggregate ensembles for the individual oligomeric states that lack a single defined quaternary structure during the pre-nucleation phase. To gain insight into the conformational space sampled in early aggregates, we probed their substructure and found emerging β-sheet subunit layers and a multitude of ordered intermolecular β-structure motifs with growing aggregate size. Among those, anti-parallel out-of-register β-strands compatible with toxic β-barrel oligomers were particularly prevalent already in smaller aggregates and formed prior to ordered fibrillar structure elements. Notably, also distinct fibril-like conformations emerged in the oligomeric state and underscore the notion that pre-nucleated oligomers serve as a critical intermediate step on-pathway to fibrils. PMID:27616019

Spatially Restricted and Developmentally Dynamic Expression of Engrailed Genes in Multiple Cerebellar Cell Types

PubMed Central

Wilson, Sandra L.; Kalinovsky, Anna; Orvis, Grant D.

2011-01-01

The cerebellum is a highly organized structure partitioned into lobules along the anterior–posterior (A-P) axis and into striped molecular domains along the medial–lateral (M-L) axis. The Engrailed (En) homeobox genes are required for patterning the morphological and molecular domains along both axes, as well as for the establishment of the normal afferent topography required to generate a fully functional cerebellum. As a means to understand how the En genes regulate multiple levels of cerebellum construction, we characterized En1 and En2 expression around birth and at postnatal day (P)21 during the period when the cerebellum undergoes a remarkable transformation from a smooth ovoid structure to a highly foliated structure. We show that both En1 and En2 are expressed in many neuronal cell types in the cerebellum, and expression persists until at least P21. En1 and En2 expression, however, undergoes profound changes in their cellular and spatial distributions between embryonic stages and P21, and their expression domains become largely distinct. Comparison of the distribution of En-expressing Purkinje cells relative to early- and late-onset Purkinje cell M-L stripe proteins revealed that although En1- and En2-expressing Purkinje cell domains do not strictly align with those of ZEBRINII at P21, a clear pattern exists that is most evident at E17.5 by an inverse correlation between the level of En2 expression and PLCβ4 and EPHA4. PMID:21431469

Profiling the array of Ca(v)3.1 variants from the human T-type calcium channel gene CACNA1G: alternative structures, developmental expression, and biophysical variations.

PubMed

Emerick, Mark C; Stein, Rebecca; Kunze, Robin; McNulty, Megan M; Regan, Melissa R; Hanck, Dorothy A; Agnew, William S

2006-08-01

We describe the regulated transcriptome of CACNA1G, a human gene for T-type Ca(v)3.1 calcium channels that is subject to extensive alternative RNA splicing. Fifteen sites of transcript variation include 2 alternative 5'-UTR promoter sites, 2 alternative 3'-UTR polyadenylation sites, and 11 sites of alternative splicing within the open reading frame. A survey of 1580 fetal and adult human brain full-length complementary DNAs reveals a family of 30 distinct transcripts, including multiple functional forms that vary in expression with development. Statistical analyses of fetal and adult transcript populations reveal patterns of linkages among intramolecular splice site configurations that change dramatically with development. A shift from nearly independent, biased splicing in fetal transcripts to strongly concerted splicing in adult transcripts suggests progressive activation of multiple "programs" of splicing regulation that reorganize molecular structures in differentiating cells. Patch-clamp studies of nine selected variants help relate splicing regulation to permutations of the gating parameters most likely to modify T-channel physiology in expressing neurons. Gating behavior reflects combinatorial interactions between variable domains so that molecular phenotype depends on ensembles of coselected domains, consistent with the observed emergence of concerted splicing during development. We conclude that the structural gene and networks of splicing regulatory factors define an integrated system for the phenotypic variation of Ca(v)3.1 biophysics during nervous system development. Copyright 2006 Wiley-Liss, Inc.

Characterizing mercury concentrations and flux dynamics in a coastal plain watershed using multiple models

EPA Science Inventory

The primary goal was to asess Hg cycling within a small coastal plain watershed (McTier Creek) using multiple watershed models with distinct mathematical frameworks that emphasize different system dynamics; a secondary goal was to identify current needs in watershed-scale Hg mode...

Adolescent Racial Identity: Self-Identification of Multiple and "Other" Race/Ethnicities

ERIC Educational Resources Information Center

Harris, Bryn; Ravert, Russell D.; Sullivan, Amanda L.

2017-01-01

This mixed methods study focused on adolescents who rejected conventional singular racial/ethnic categorization by selecting multiple race/ethnicities or writing descriptions of "Other" racial/ethnic identities in response to a survey item asking them to identify their race/ethnicity. Written responses reflected eight distinct categories…

Molecular Diversity of Cyanobacteria Inhabiting Coniform Structures and Surrounding Mat in a Yellowstone Hot Spring

NASA Astrophysics Data System (ADS)

Lau, Evan; Nash, Cody Z.; Vogler, Detlev R.; Cullings, K. W.

2005-02-01

Lithified coniform structures are common within cyanobacterial mats in Yellowstone National Park hot springs. It is unknown whether these structures and the mats from which they develop are inhabited by the same cyanobacterial populations. Denaturing gradient gel electrophoresis and sequencing and phylogenetic analysis of 16S rDNA was used to determine whether (1) three different morphological types of lithified coniform structures are inhabited by different cyanobacterial species, (2) these species are partitioned along a vertical gradient of these structures, and (3) lithified and non-lithified sections of mat are inhabited by different cyanobacterial species. Our results, based on multiple samplings, indicate that the cyanobacterial community compositions in the three lithified morphological types were identical and lacked any vertical differentiation. However, lithified and non-lithified portions of the same mat were inhabited by distinct and different populations of cyanobacteria. Cyanobacteria inhabiting lithified structures included at least one undefined Oscillatorialean taxon, which may represent the dominant cyanobacteria genus in lithified coniform stromatolites, Phormidium, three Synechococcus-like species, and two unknown cyanobacterial taxa. In contrast, the surrounding mats contained four closely related Synechococcus-like species. Our results indicate that the distribution of lithified coniform stromatolites may be dependent on the presence of one or more microorganisms, which are phylogenetically different from those inhabiting surrounding non-lithified mats.

Long-term impact of hydrological regime on structure and functions of microbial communities in riverine wetland sediments.

PubMed

Foulquier, Arnaud; Volat, Bernadette; Neyra, Marc; Bornette, Gudrun; Montuelle, Bernard

2013-08-01

In a context of global change, alterations in the water cycle may impact the structure and function of terrestrial and aquatic ecosystems. Wetlands are particularly at risk because hydrological regime has a major influence on microbially mediated biogeochemical processes in sediments. While the influence of water availability on wetland biogeochemical processes has been comprehensively studied, the influence of hydrological regime on microbial community structure has been overlooked. We tested for the effect of hydrological regime on the structure and functions of microbial communities by comparing sediments collected at multiple sites in the Ain département (Eastern France). Each site consisted of two plots, one permanently and one seasonally inundated. At the time of sampling, all plots were continuously inundated for more than 6 months but still harboured distinct bacterial communities. This change in community structure was not associated with marked modifications in the rates of microbial activities involved in the C and N cycles. These results suggest that the observed structural change could be related to bacterial taxa responding to the environmental variations associated with different hydrological regimes, but not strongly associated with the biogeochemical processes monitored here. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Wanting, liking, and preference construction.

PubMed

Dai, Xianchi; Brendl, C Miguel; Ariely, Dan

2010-06-01

According to theories on preference construction, multiple preferences result from multiple contexts (e.g., loss vs. gain frames). This implies that people can have different representations of a preference in different contexts. Drawing on Berridge's (1999) distinction between unconscious liking and wanting, we hypothesize that people may have multiple representations of a preference toward an object even within a single context. Specifically, we propose that people can have different representations of an object's motivational value, or incentive value, versus its emotional value, or likability, even when the object is placed in the same context. Study 1 establishes a divergence between incentive value and likability of faces using behavioral measures. Studies 2A and 2B, using self-report measures, provide support for our main hypothesis that people are perfectly aware of these distinct representations and are able to access them concurrently at will. We also discuss implications of our findings for the truism that people seek pleasure and for expectancy-value theories.

Market segmentation for multiple option healthcare delivery systems--an application of cluster analysis.

PubMed

Jarboe, G R; Gates, R H; McDaniel, C D

1990-01-01

Healthcare providers of multiple option plans may be confronted with special market segmentation problems. This study demonstrates how cluster analysis may be used for discovering distinct patterns of preference for multiple option plans. The availability of metric, as opposed to categorical or ordinal, data provides the ability to use sophisticated analysis techniques which may be superior to frequency distributions and cross-tabulations in revealing preference patterns.

Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis.

PubMed

Khavari, Rose; Karmonik, Christof; Shy, Michael; Fletcher, Sophie; Boone, Timothy

2017-02-01

Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas of interest for future intervention. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Seven-pass transmembrane cadherins: roles and emerging mechanisms in axonal and dendritic patterning.

PubMed

Berger-Müller, Sandra; Suzuki, Takashi

2011-12-01

The Flamingo/Celsr seven-transmembrane cadherins represent a conserved subgroup of the cadherin superfamily involved in multiple aspects of development. In the developing nervous system, Fmi/Celsr control axonal blueprint and dendritic morphogenesis from invertebrates to mammals. As expected from their molecular structure, seven-transmembrane cadherins can induce cell-cell homophilic interactions but also intracellular signaling. Fmi/Celsr is known to regulate planar cell polarity (PCP) through interactions with PCP proteins. In the nervous system, Fmi/Celsr can function in collaboration with or independently of other PCP genes. Here, we focus on recent studies which show that seven-transmembrane cadherins use distinct molecular mechanisms to achieve diverse functions in the development of the nervous system.

Distribution and function of voltage-gated sodium channels in the nervous system.

PubMed

Wang, Jun; Ou, Shao-Wu; Wang, Yun-Jie

2017-11-02

Voltage-gated sodium channels (VGSCs) are the basic ion channels for neuronal excitability, which are crucial for the resting potential and the generation and propagation of action potentials in neurons. To date, at least nine distinct sodium channel isoforms have been detected in the nervous system. Recent studies have identified that voltage-gated sodium channels not only play an essential role in the normal electrophysiological activities of neurons but also have a close relationship with neurological diseases. In this study, the latest research findings regarding the structure, type, distribution, and function of VGSCs in the nervous system and their relationship to neurological diseases, such as epilepsy, neuropathic pain, brain tumors, neural trauma, and multiple sclerosis, are reviewed in detail.

Protocols for the Design of Kinase-focused Compound Libraries.

PubMed

Jacoby, Edgar; Wroblowski, Berthold; Buyck, Christophe; Neefs, Jean-Marc; Meyer, Christophe; Cummings, Maxwell D; van Vlijmen, Herman

2018-05-01

Protocols for the design of kinase-focused compound libraries are presented. Kinase-focused compound libraries can be differentiated based on the design goal. Depending on whether the library should be a discovery library specific for one particular kinase, a general discovery library for multiple distinct kinase projects, or even phenotypic screening, there exists today a variety of in silico methods to design candidate compound libraries. We address the following scenarios: 1) Datamining of SAR databases and kinase focused vendor catalogues; 2) Predictions and virtual screening; 3) Structure-based design of combinatorial kinase inhibitors; 4) Design of covalent kinase inhibitors; 5) Design of macrocyclic kinase inhibitors; and 6) Design of allosteric kinase inhibitors and activators. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Field enhancement of multiphoton induced luminescence processes in ZnO nanorods

NASA Astrophysics Data System (ADS)

Hyyti, Janne; Perestjuk, Marko; Mahler, Felix; Grunwald, Rüdiger; Güell, Frank; Gray, Ciarán; McGlynn, Enda; Steinmeyer, Günter

2018-03-01

The near-ultraviolet photoluminescence of ZnO nanorods induced by multiphoton absorption of unamplified Ti:sapphire pulses is investigated. Power dependence measurements have been conducted with an adaptation of the ultrashort pulse characterization method of interferometric frequency-resolved optical gating. These measurements enable the separation of second harmonic and photoluminescence bands due to their distinct coherence properties. A detailed analysis yields fractional power dependence exponents in the range of 3-4, indicating the presence of multiple nonlinear processes. The range in measured exponents is attributed to differences in local field enhancement, which is supported by independent photoluminescence and structural measurements. Simulations based on Keldysh theory suggest contributions by three- and four-photon absorption as well as avalanche ionization in agreement with experimental findings.

Impact of heat-shock protein 90 on cancer metastasis

PubMed Central

Tsutsumi, Shinji; Beebe, Kristin; Neckers, Len

2009-01-01

Cancer metastasis is the result of complex processes, including alteration of cell adhesion/motility in the microenvironment and neoangiogenesis, that are necessary to support cancer growth in tissues distant from the primary tumor. The molecular chaperone heat-shock protein 90 (Hsp90), also termed the ‘cancer chaperone’, plays a crucial role in maintaining the stability and activity of numerous signaling proteins involved in these processes. Small-molecule Hsp90 inhibitors display anticancer activity both in vitro and in vivo, and multiple Phase II and Phase III clinical trials of several structurally distinct Hsp90 inhibitors are currently underway. In this review, we will highlight the importance of Hsp90 in cancer metastasis and the therapeutic potential of Hsp90 inhibitors as antimetastasis drugs. PMID:19519207

Shortest-path constraints for 3D multiobject semiautomatic segmentation via clustering and Graph Cut.

PubMed

Kéchichian, Razmig; Valette, Sébastien; Desvignes, Michel; Prost, Rémy

2013-11-01

We derive shortest-path constraints from graph models of structure adjacency relations and introduce them in a joint centroidal Voronoi image clustering and Graph Cut multiobject semiautomatic segmentation framework. The vicinity prior model thus defined is a piecewise-constant model incurring multiple levels of penalization capturing the spatial configuration of structures in multiobject segmentation. Qualitative and quantitative analyses and comparison with a Potts prior-based approach and our previous contribution on synthetic, simulated, and real medical images show that the vicinity prior allows for the correct segmentation of distinct structures having identical intensity profiles and improves the precision of segmentation boundary placement while being fairly robust to clustering resolution. The clustering approach we take to simplify images prior to segmentation strikes a good balance between boundary adaptivity and cluster compactness criteria furthermore allowing to control the trade-off. Compared with a direct application of segmentation on voxels, the clustering step improves the overall runtime and memory footprint of the segmentation process up to an order of magnitude without compromising the quality of the result.

Contrasting population structure from nuclear intron sequences and mtDNA of humpback whales.

PubMed

Palumbi, S R; Baker, C S

1994-05-01

Powerful analyses of population structure require information from multiple genetic loci. To help develop a molecular toolbox for obtaining this information, we have designed universal oligonucleotide primers that span conserved intron-exon junctions in a wide variety of animal phyla. We test the utility of exon-primed, intron-crossing amplifications by analyzing the variability of actin intron sequences from humpback, blue, and bowhead whales and comparing the results with mitochondrial DNA (mtDNA) haplotype data. Humpback actin introns fall into two major clades that exist in different frequencies in different oceanic populations. It is surprising that Hawaii and California populations, which are very distinct in mtDNAs, are similar in actin intron alleles. This discrepancy between mtDNA and nuclear DNA results may be due either to differences in genetic drift in mitochondrial and nuclear genes or to preferential movement of males, which do not transmit mtDNA to offspring, between separate breeding grounds. Opposing mtDNA and nuclear DNA results can help clarify otherwise hidden patterns of structure in natural populations.

Modular assembly of thick multifunctional cardiac patches

PubMed Central

Fleischer, Sharon; Shapira, Assaf; Feiner, Ron; Dvir, Tal

2017-01-01

In cardiac tissue engineering cells are seeded within porous biomaterial scaffolds to create functional cardiac patches. Here, we report on a bottom-up approach to assemble a modular tissue consisting of multiple layers with distinct structures and functions. Albumin electrospun fiber scaffolds were laser-patterned to create microgrooves for engineering aligned cardiac tissues exhibiting anisotropic electrical signal propagation. Microchannels were patterned within the scaffolds and seeded with endothelial cells to form closed lumens. Moreover, cage-like structures were patterned within the scaffolds and accommodated poly(lactic-co-glycolic acid) (PLGA) microparticulate systems that controlled the release of VEGF, which promotes vascularization, or dexamethasone, an anti-inflammatory agent. The structure, morphology, and function of each layer were characterized, and the tissue layers were grown separately in their optimal conditions. Before transplantation the tissue and microparticulate layers were integrated by an ECM-based biological glue to form thick 3D cardiac patches. Finally, the patches were transplanted in rats, and their vascularization was assessed. Because of the simple modularity of this approach, we believe that it could be used in the future to assemble other multicellular, thick, 3D, functional tissues. PMID:28167795

Multiple capsid-stabilizing interactions revealed in a high-resolution structure of an emerging picornavirus causing neonatal sepsis

NASA Astrophysics Data System (ADS)

Shakeel, Shabih; Westerhuis, Brenda M.; Domanska, Ausra; Koning, Roman I.; Matadeen, Rishi; Koster, Abraham J.; Bakker, Arjen Q.; Beaumont, Tim; Wolthers, Katja C.; Butcher, Sarah J.

2016-07-01

The poorly studied picornavirus, human parechovirus 3 (HPeV3) causes neonatal sepsis with no therapies available. Our 4.3-Å resolution structure of HPeV3 on its own and at 15 Å resolution in complex with human monoclonal antibody Fabs demonstrates the expected picornavirus capsid structure with three distinct features. First, 25% of the HPeV3 RNA genome in 60 sites is highly ordered as confirmed by asymmetric reconstruction, and interacts with conserved regions of the capsid proteins VP1 and VP3. Second, the VP0 N terminus stabilizes the capsid inner surface, in contrast to other picornaviruses where on expulsion as VP4, it forms an RNA translocation channel. Last, VP1's hydrophobic pocket, the binding site for the antipicornaviral drug, pleconaril, is blocked and thus inappropriate for antiviral development. Together, these results suggest a direction for development of neutralizing antibodies, antiviral drugs based on targeting the RNA-protein interactions and dissection of virus assembly on the basis of RNA nucleation.

Family life course transitions and rural household economy during China's market reform.

PubMed

Chen, Feinian; Korinek, Kim

2010-11-01

This article investigates the effect of family life course transitions on labor allocation strategies in rural Chinese households. We highlight three types of economic activity that involve reallocation of household labor oriented toward a more diversified, nonfarm rural economy: involvement in wage employment, household entrepreneurship, and/or multiple activities that span economic sectors. With the use of data from the China Health and Nutrition Survey (CHNS 1997, 2000, and 2004), our longitudinal analyses of rural household economic activity point to the significance of household demography, life course transitions, and local economic structures as factors facilitating household labor reallocation. First, as expected, a relatively youthful household structure is conducive to innovative economic behavior. Second, household entrances and exits are significant, but their impacts are not equal. Life events such as births, deaths, marriage, or leaving home for school or employment affect household economy in distinctive ways. Finally, the reallocations of household labor undertaken by households are shaped by local economic structures: in particular, the extent of village-level entrepreneurial activity, off-farm employment, and out-migration.

cis-Golgi proteins accumulate near the ER exit sites and act as the scaffold for Golgi regeneration after brefeldin A treatment in tobacco BY-2 cells

PubMed Central

Ito, Yoko; Uemura, Tomohiro; Shoda, Keiko; Fujimoto, Masaru; Ueda, Takashi; Nakano, Akihiko

2012-01-01

The Golgi apparatus forms stacks of cisternae in many eukaryotic cells. However, little is known about how such a stacked structure is formed and maintained. To address this question, plant cells provide a system suitable for live-imaging approaches because individual Golgi stacks are well separated in the cytoplasm. We established tobacco BY-2 cell lines expressing multiple Golgi markers tagged by different fluorescent proteins and observed their responses to brefeldin A (BFA) treatment and BFA removal. BFA treatment disrupted cis, medial, and trans cisternae but caused distinct relocalization patterns depending on the proteins examined. Medial- and trans-Golgi proteins, as well as one cis-Golgi protein, were absorbed into the endoplasmic reticulum (ER), but two other cis-Golgi proteins formed small punctate structures. After BFA removal, these puncta coalesced first, and then the Golgi stacks regenerated from them in the cis-to-trans order. We suggest that these structures have a property similar to the ER-Golgi intermediate compartment and function as the scaffold of Golgi regeneration. PMID:22740633

cis-Golgi proteins accumulate near the ER exit sites and act as the scaffold for Golgi regeneration after brefeldin A treatment in tobacco BY-2 cells.

PubMed

Ito, Yoko; Uemura, Tomohiro; Shoda, Keiko; Fujimoto, Masaru; Ueda, Takashi; Nakano, Akihiko

2012-08-01

The Golgi apparatus forms stacks of cisternae in many eukaryotic cells. However, little is known about how such a stacked structure is formed and maintained. To address this question, plant cells provide a system suitable for live-imaging approaches because individual Golgi stacks are well separated in the cytoplasm. We established tobacco BY-2 cell lines expressing multiple Golgi markers tagged by different fluorescent proteins and observed their responses to brefeldin A (BFA) treatment and BFA removal. BFA treatment disrupted cis, medial, and trans cisternae but caused distinct relocalization patterns depending on the proteins examined. Medial- and trans-Golgi proteins, as well as one cis-Golgi protein, were absorbed into the endoplasmic reticulum (ER), but two other cis-Golgi proteins formed small punctate structures. After BFA removal, these puncta coalesced first, and then the Golgi stacks regenerated from them in the cis-to-trans order. We suggest that these structures have a property similar to the ER-Golgi intermediate compartment and function as the scaffold of Golgi regeneration.

Scop3D: three-dimensional visualization of sequence conservation.

PubMed

Vermeire, Tessa; Vermaere, Stijn; Schepens, Bert; Saelens, Xavier; Van Gucht, Steven; Martens, Lennart; Vandermarliere, Elien

2015-04-01

The integration of a protein's structure with its known sequence variation provides insight on how that protein evolves, for instance in terms of (changing) function or immunogenicity. Yet, collating the corresponding sequence variants into a multiple sequence alignment, calculating each position's conservation, and mapping this information back onto a relevant structure is not straightforward. We therefore built the Sequence Conservation on Protein 3D structure (scop3D) tool to perform these tasks automatically. The output consists of two modified PDB files in which the B-values for each position are replaced by the percentage sequence conservation, or the information entropy for each position, respectively. Furthermore, text files with absolute and relative amino acid occurrences for each position are also provided, along with snapshots of the protein from six distinct directions in space. The visualization provided by scop3D can for instance be used as an aid in vaccine development or to identify antigenic hotspots, which we here demonstrate based on an analysis of the fusion proteins of human respiratory syncytial virus and mumps virus. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Family Life Course Transitions and Rural Household Economy During China’s Market Reform

PubMed Central

CHEN, FEINIAN; KORINEK, KIM

2010-01-01

This article investigates the effect of family life course transitions on labor allocation strategies in rural Chinese households. We highlight three types of economic activity that involve reallocation of household labor oriented toward a more diversified, nonfarm rural economy: involvement in wage employment, household entrepreneurship, and/or multiple activities that span economic sectors. With the use of data from the China Health and Nutrition Survey (CHNS 1997, 2000, and 2004), our longitudinal analyses of rural household economic activity point to the significance of household demography, life course transitions, and local economic structures as factors facilitating household labor reallocation. First, as expected, a relatively youthful household structure is conducive to innovative economic behavior. Second, household entrances and exits are significant, but their impacts are not equal. Life events such as births, deaths, marriage, or leaving home for school or employment affect household economy in distinctive ways. Finally, the reallocations of household labor undertaken by households are shaped by local economic structures: in particular, the extent of village-level entrepreneurial activity, off-farm employment, and out-migration. PMID:21308566

The Role of Electron Microscopy in Studying the Continuum of Changes in Membranous Structures during Poliovirus Infection

PubMed Central

Rossignol, Evan D.; Yang, Jie E.; Bullitt, Esther

2015-01-01

Replication of the poliovirus genome is localized to cytoplasmic replication factories that are fashioned out of a mixture of viral proteins, scavenged cellular components, and new components that are synthesized within the cell due to viral manipulation/up-regulation of protein and phospholipid synthesis. These membranous replication factories are quite complex, and include markers from multiple cytoplasmic cellular organelles. This review focuses on the role of electron microscopy in advancing our understanding of poliovirus RNA replication factories. Structural data from the literature provide the basis for interpreting a wide range of biochemical studies that have been published on virus-induced lipid biosynthesis. In combination, structural and biochemical experiments elucidate the dramatic membrane remodeling that is a hallmark of poliovirus infection. Temporal and spatial membrane modifications throughout the infection cycle are discussed. Early electron microscopy studies of morphological changes following viral infection are re-considered in light of more recent data on viral manipulation of lipid and protein biosynthesis. These data suggest the existence of distinct subcellular vesicle populations, each of which serves specialized roles in poliovirus replication processes. PMID:26473912

Plate tectonics of virus shell assembly and reorganization in phage φ8, a distant relative of mammalian reoviruses.

PubMed

El Omari, Kamel; Sutton, Geoff; Ravantti, Janne J; Zhang, Hanwen; Walter, Thomas S; Grimes, Jonathan M; Bamford, Dennis H; Stuart, David I; Mancini, Erika J

2013-08-06

The hallmark of a virus is its capsid, which harbors the viral genome and is formed from protein subunits, which assemble following precise geometric rules. dsRNA viruses use an unusual protein multiplicity (120 copies) to form their closed capsids. We have determined the atomic structure of the capsid protein (P1) from the dsRNA cystovirus Φ8. In the crystal P1 forms pentamers, very similar in shape to facets of empty procapsids, suggesting an unexpected assembly pathway that proceeds via a pentameric intermediate. Unlike the elongated proteins used by dsRNA mammalian reoviruses, P1 has a compact trapezoid-like shape and a distinct arrangement in the shell, with two near-identical conformers in nonequivalent structural environments. Nevertheless, structural similarity with the analogous protein from the mammalian viruses suggests a common ancestor. The unusual shape of the molecule may facilitate dramatic capsid expansion during phage maturation, allowing P1 to switch interaction interfaces to provide capsid plasticity. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Choosing a DIVA: a comparison of emerging digital imagery vegetation analysis techniques

USGS Publications Warehouse

Jorgensen, Christopher F.; Stutzman, Ryan J.; Anderson, Lars C.; Decker, Suzanne E.; Powell, Larkin A.; Schacht, Walter H.; Fontaine, Joseph J.

2013-01-01

Question: What is the precision of five methods of measuring vegetation structure using ground-based digital imagery and processing techniques? Location: Lincoln, Nebraska, USA Methods: Vertical herbaceous cover was recorded using digital imagery techniques at two distinct locations in a mixed-grass prairie. The precision of five ground-based digital imagery vegetation analysis (DIVA) methods for measuring vegetation structure was tested using a split-split plot analysis of covariance. Variability within each DIVA technique was estimated using coefficient of variation of mean percentage cover. Results: Vertical herbaceous cover estimates differed among DIVA techniques. Additionally, environmental conditions affected the vertical vegetation obstruction estimates for certain digital imagery methods, while other techniques were more adept at handling various conditions. Overall, percentage vegetation cover values differed among techniques, but the precision of four of the five techniques was consistently high. Conclusions: DIVA procedures are sufficient for measuring various heights and densities of standing herbaceous cover. Moreover, digital imagery techniques can reduce measurement error associated with multiple observers' standing herbaceous cover estimates, allowing greater opportunity to detect patterns associated with vegetation structure.

Factorial structure of the 'ToM Storybooks': A test evaluating multiple components of Theory of Mind.

PubMed

Bulgarelli, Daniela; Testa, Silvia; Molina, Paola

2015-06-01

This study examined the factorial structure of the Theory of Mind (ToM) Storybooks, a comprehensive 93-item instrument tapping the five components in Wellman's model of ToM (emotion recognition, understanding of desire and beliefs, ability to distinguish between physical and mental entities, and awareness of the link between perception and knowledge). A sample of 681 three- to eight-year-old Italian children was divided into three age groups to assess whether factorial structure varied across different age ranges. Partial credit model analysis was applied to the data, leading to the empirical identification of 23 composite variables aggregating the ToM Storybooks items. Confirmatory factor analysis was then conducted on the composite variables, providing support for the theoretical model. There were partial differences in the specific composite variables making up the dimensions for each of the three age groups. A single test evaluating distinct dimensions of ToM is a valuable resource for clinical practice which may be used to define differential profiles for specific populations. © 2014 The British Psychological Society.

Using Pinochle to Motivate the Restricted Combinations with Repetitions Problem

ERIC Educational Resources Information Center

Gorman, Patrick S.; Kunkel, Jeffrey D.; Vasko, Francis J.

2011-01-01

A standard example used in introductory combinatoric courses is to count the number of five-card poker hands possible from a straight deck of 52 distinct cards. A more interesting problem is to count the number of distinct hands possible from a Pinochle deck in which there are multiple, but obviously limited, copies of each type of card (two…

An ambiguity principle for assigning protein structural domains.

PubMed

Postic, Guillaume; Ghouzam, Yassine; Chebrek, Romain; Gelly, Jean-Christophe

2017-01-01

Ambiguity is the quality of being open to several interpretations. For an image, it arises when the contained elements can be delimited in two or more distinct ways, which may cause confusion. We postulate that it also applies to the analysis of protein three-dimensional structure, which consists in dividing the molecule into subunits called domains. Because different definitions of what constitutes a domain can be used to partition a given structure, the same protein may have different but equally valid domain annotations. However, knowledge and experience generally displace our ability to accept more than one way to decompose the structure of an object-in this case, a protein. This human bias in structure analysis is particularly harmful because it leads to ignoring potential avenues of research. We present an automated method capable of producing multiple alternative decompositions of protein structure (web server and source code available at www.dsimb.inserm.fr/sword/). Our innovative algorithm assigns structural domains through the hierarchical merging of protein units, which are evolutionarily preserved substructures that describe protein architecture at an intermediate level, between domain and secondary structure. To validate the use of these protein units for decomposing protein structures into domains, we set up an extensive benchmark made of expert annotations of structural domains and including state-of-the-art domain parsing algorithms. The relevance of our "multipartitioning" approach is shown through numerous examples of applications covering protein function, evolution, folding, and structure prediction. Finally, we introduce a measure for the structural ambiguity of protein molecules.

A non-canonical DNA structure enables homologous recombination in various genetic systems.

PubMed

Masuda, Tokiha; Ito, Yutaka; Terada, Tohru; Shibata, Takehiko; Mikawa, Tsutomu

2009-10-30

Homologous recombination, which is critical to genetic diversity, depends on homologous pairing (HP). HP is the switch from parental to recombinant base pairs, which requires expansion of inter-base pair spaces. This expansion unavoidably causes untwisting of the parental double-stranded DNA. RecA/Rad51-catalyzed ATP-dependent HP is extensively stimulated in vitro by negative supercoils, which compensates for untwisting. However, in vivo, double-stranded DNA is relaxed by bound proteins and thus is an unfavorable substrate for RecA/Rad51. In contrast, Mhr1, an ATP-independent HP protein required for yeast mitochondrial homologous recombination, catalyzes HP without the net untwisting of double-stranded DNA. Therefore, we questioned whether Mhr1 uses a novel strategy to promote HP. Here, we found that, like RecA, Mhr1 induced the extension of bound single-stranded DNA. In addition, this structure was induced by all evolutionarily and structurally distinct HP proteins so far tested, including bacterial RecO, viral RecT, and human Rad51. Thus, HP includes the common non-canonical DNA structure and uses a common core mechanism, independent of the species of HP proteins. We discuss the significance of multiple types of HP proteins.

Structural Characterization of Proline-rich Tyrosine Kinase 2 (PYK2) Reveals a Unique (DFG-out) Conformation and Enables Inhibitor Design

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

Han, Seungil; Mistry, Anil; Chang, Jeanne S.

Proline-rich tyrosine kinase 2 (PYK2) is a cytoplasmic, non-receptor tyrosine kinase implicated in multiple signaling pathways. It is a negative regulator of osteogenesis and considered a viable drug target for osteoporosis treatment. The high-resolution structures of the human PYK2 kinase domain with different inhibitor complexes establish the conventional bilobal kinase architecture and show the conformational variability of the DFG loop. The basis for the lack of selectivity for the classical kinase inhibitor, PF-431396, within the FAK family is explained by our structural analyses. Importantly, the novel DFG-out conformation with two diarylurea inhibitors (BIRB796, PF-4618433) reveals a distinct subclass of non-receptormore » tyrosine kinases identifiable by the gatekeeper Met-502 and the unique hinge loop conformation of Leu-504. This is the first example of a leucine residue in the hinge loop that blocks the ATP binding site in the DFG-out conformation. Our structural, biophysical, and pharmacological studies suggest that the unique features of the DFG motif, including Leu-504 hinge-loop variability, can be exploited for the development of selective protein kinase inhibitors.« less

The taxonomic distinctness of macroinvertebrate communities of Atlantic Forest streams cannot be predicted by landscape and climate variables, but traditional biodiversity indices can.

PubMed

Roque, F O; Guimarães, E A; Ribeiro, M C; Escarpinati, S C; Suriano, M T; Siqueira, T

2014-11-01

Predicting how anthropogenic activities may influence the various components of biodiversity is essential for finding ways to reduce diversity loss. This challenge involves: a) understanding how environmental factors influence diversity across different spatial scales, and b) developing ways to measure these relationships in a way that is fast, economical, and easy to communicate. In this study, we investigate whether landscape and bioclimatic variables could explain variation in biodiversity indices in macroinvertebrate communities from 39 Atlantic Forest streams. In addition to traditional diversity measures, i.e., species richness, abundance and Shannon index, we used a taxonomic distinctness index that measures the degree of phylogenetic relationship among taxa. The amount of variation in the diversity measures that was explained by environmental and spatial variables was estimated using variation partitioning based on multiple regression. Our study demonstrates that taxonomic distinctness does not respond in the same way as the traditional used in biodiversity studies. We found no evidence that taxonomic distinctness responds predictably to variation in landscape metrics, indicating the need for the incorporation of predictors at multiple scales in this type of study. The lack of congruence between taxonomic distinctness and other indices and its low predictability may be related to the fact that this measure expresses long-term evolutionary adaptation to ecosystem conditions, while the other traditional biodiversity metrics respond to short-term environmental changes.

The Theory of Multiple Intelligences: A Case of Missing Cognitive Matter.

ERIC Educational Resources Information Center

Allix, Nicholas M.

2000-01-01

Argues that although Gardner's conception of human cognition, characterized by a set of multiple and distinct cognitive capabilities, is an advance over the narrow conception of IQ, it runs into fundamental difficulties of a methodological kind and is based on a discredited empiricist theory of knowledge which work with artificial neural networks…

MULTIPLE ENZYME RESTRICTION FRAGMENT LENGTH POLYMORPHISM ANALYSIS FOR HIGH RESOLUTION DISTINCTION OF PSEUDOMONAS (SENSU STRICTO) 16S RRNA GENES

EPA Science Inventory

Pseudomonas specific 16S rDNA PCR amplification and multiple enzyme restriction fragment length polymorphism (MERFLP) analysis using a single digestion mixture of Alu I, Hinf I, Rsa I, and Tru 9I distinguished 150 published sequences and reference strains of authentic Pseudomonas...

Measurement Invariance for Latent Constructs in Multiple Populations: A Critical View and Refocus

ERIC Educational Resources Information Center

Raykov, Tenko; Marcoulides, George A.; Li, Cheng-Hsien

2012-01-01

Popular measurement invariance testing procedures for latent constructs evaluated by multiple indicators in distinct populations are revisited and discussed. A frequently used test of factor loading invariance is shown to possess serious limitations that in general preclude it from accomplishing its goal of ascertaining this invariance. A process…

Alterity: Learning Polyvalent Selves, Resisting Disabling Notions of the Self

ERIC Educational Resources Information Center

Walker, Wayland

2011-01-01

This article queries how one type of human difference--alterity, the experience of multiple distinct consciousnesses, or "alters," by one person--is pathologized in American culture. This experience is inscribed as a mental illness, labeled now as dissociative identity disorder (DID) and formerly known as multiple personality disorder (MPD). In…

Multiple Disabilities and Visual Impairment: An Action Research Project

ERIC Educational Resources Information Center

Argyropoulos, Vassilios; Thymakis, Paraskevas

2014-01-01

Children with visual and motor disabilities constitute a distinct group with a unique set of educational needs. Such children are often grouped with the broader population of children with multiple disabilities and visual impairments (that is, those who are blind or have low vision) (Erin, 2000; McLinden, 1997). The chief characteristic of…

Distinct Roles of Dopamine and Subthalamic Nucleus in Learning and Probabilistic Decision Making

ERIC Educational Resources Information Center

Coulthard, Elizabeth J.; Bogacz, Rafal; Javed, Shazia; Mooney, Lucy K.; Murphy, Gillian; Keeley, Sophie; Whone, Alan L.

2012-01-01

Even simple behaviour requires us to make decisions based on combining multiple pieces of learned and new information. Making such decisions requires both learning the optimal response to each given stimulus as well as combining probabilistic information from multiple stimuli before selecting a response. Computational theories of decision making…

Visualization and dissemination of multidimensional proteomics data comparing protein abundance during Caenorhabditis elegans development.

PubMed

Riffle, Michael; Merrihew, Gennifer E; Jaschob, Daniel; Sharma, Vagisha; Davis, Trisha N; Noble, William S; MacCoss, Michael J

2015-11-01

Regulation of protein abundance is a critical aspect of cellular function, organism development, and aging. Alternative splicing may give rise to multiple possible proteoforms of gene products where the abundance of each proteoform is independently regulated. Understanding how the abundances of these distinct gene products change is essential to understanding the underlying mechanisms of many biological processes. Bottom-up proteomics mass spectrometry techniques may be used to estimate protein abundance indirectly by sequencing and quantifying peptides that are later mapped to proteins based on sequence. However, quantifying the abundance of distinct gene products is routinely confounded by peptides that map to multiple possible proteoforms. In this work, we describe a technique that may be used to help mitigate the effects of confounding ambiguous peptides and multiple proteoforms when quantifying proteins. We have applied this technique to visualize the distribution of distinct gene products for the whole proteome across 11 developmental stages of the model organism Caenorhabditis elegans. The result is a large multidimensional dataset for which web-based tools were developed for visualizing how translated gene products change during development and identifying possible proteoforms. The underlying instrument raw files and tandem mass spectra may also be downloaded. The data resource is freely available on the web at http://www.yeastrc.org/wormpes/ . Graphical Abstract ᅟ.

Visualization and Dissemination of Multidimensional Proteomics Data Comparing Protein Abundance During Caenorhabditis elegans Development

NASA Astrophysics Data System (ADS)

Riffle, Michael; Merrihew, Gennifer E.; Jaschob, Daniel; Sharma, Vagisha; Davis, Trisha N.; Noble, William S.; MacCoss, Michael J.

2015-11-01

Regulation of protein abundance is a critical aspect of cellular function, organism development, and aging. Alternative splicing may give rise to multiple possible proteoforms of gene products where the abundance of each proteoform is independently regulated. Understanding how the abundances of these distinct gene products change is essential to understanding the underlying mechanisms of many biological processes. Bottom-up proteomics mass spectrometry techniques may be used to estimate protein abundance indirectly by sequencing and quantifying peptides that are later mapped to proteins based on sequence. However, quantifying the abundance of distinct gene products is routinely confounded by peptides that map to multiple possible proteoforms. In this work, we describe a technique that may be used to help mitigate the effects of confounding ambiguous peptides and multiple proteoforms when quantifying proteins. We have applied this technique to visualize the distribution of distinct gene products for the whole proteome across 11 developmental stages of the model organism Caenorhabditis elegans. The result is a large multidimensional dataset for which web-based tools were developed for visualizing how translated gene products change during development and identifying possible proteoforms. The underlying instrument raw files and tandem mass spectra may also be downloaded. The data resource is freely available on the web at http://www.yeastrc.org/wormpes/.

Thinking science with thinking machines: The multiple realities of basic and applied knowledge in a research border zone.

PubMed

Hoffman, Steve G

2015-04-01

Some scholars dismiss the distinction between basic and applied science as passé, yet substantive assumptions about this boundary remain obdurate in research policy, popular rhetoric, the sociology and philosophy of science, and, indeed, at the level of bench practice. In this article, I draw on a multiple ontology framework to provide a more stable affirmation of a constructivist position in science and technology studies that cannot be reduced to a matter of competing perspectives on a single reality. The analysis is grounded in ethnographic research in the border zone of Artificial Intelligence science. I translate in-situ moments in which members of neighboring but differently situated labs engage in three distinct repertoires that render the reality of basic and applied science: partitioning, flipping, and collapsing. While the essences of scientific objects are nowhere to be found, the boundary between basic and applied is neither illusion nor mere propaganda. Instead, distinctions among scientific knowledge are made real as a matter of course.

Multiple Lower Extremity Mononeuropathies by Segmental Schwannomatosis: A Case Report

PubMed Central

Kwon, Na Yeon; Oh, Hyun-Mi

2015-01-01

Schwannoma is an encapsulated nerve sheath tumor that is distinct from neurofibromatosis. It is defined as the occurrence of multiple schwannomas without any bilateral vestibular schwannomas. A 46-year-old man with multiple schwannomas involving peripheral nerves of the ipsilateral lower extremity presented with neurologic symptoms. Electrodiagnostic studies revealed multiple mononeuropathies involving the left sciatic, common peroneal, tibial, femoral and superior gluteal nerves. Histologic findings confirmed the diagnosis of schwannoma. We reported this rare case of segmental schwannomatosis that presented with neurologic symptoms including motor weakness, which was confirmed as multiple mononeuropathies by electrodiagnostic studies. PMID:26605183

Multiple Lower Extremity Mononeuropathies by Segmental Schwannomatosis: A Case Report.

PubMed

Kwon, Na Yeon; Oh, Hyun-Mi; Ko, Young Jin

2015-10-01

Schwannoma is an encapsulated nerve sheath tumor that is distinct from neurofibromatosis. It is defined as the occurrence of multiple schwannomas without any bilateral vestibular schwannomas. A 46-year-old man with multiple schwannomas involving peripheral nerves of the ipsilateral lower extremity presented with neurologic symptoms. Electrodiagnostic studies revealed multiple mononeuropathies involving the left sciatic, common peroneal, tibial, femoral and superior gluteal nerves. Histologic findings confirmed the diagnosis of schwannoma. We reported this rare case of segmental schwannomatosis that presented with neurologic symptoms including motor weakness, which was confirmed as multiple mononeuropathies by electrodiagnostic studies.

The Relationship of Hypochondriasis to Anxiety, Depressive, and Somatoform Disorders.

PubMed

Scarella, Timothy M; Laferton, Johannes A C; Ahern, David K; Fallon, Brian A; Barsky, Arthur

2016-01-01

Though the phenotype of anxiety about medical illness has long been recognized, there continues to be debate as to whether it is a distinct psychiatric disorder and, if so, to which diagnostic category it belongs. Our objective was to investigate the pattern of psychiatric comorbidity in hypochondriasis (HC) and to assess the relationship of health anxiety to anxiety, depressive, and somatoform disorders. Data were collected as part of a clinical trial on treatment methods for HC. In all, 194 participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) HC were assessed by sociodemographic variables, results of structured diagnostic interviews, and validated instruments for assessing various symptom dimensions of psychopathology. Most of the individuals with HC had comorbid psychiatric illness; the mean number of comorbid diagnoses was 1.4, and 35.1% had HC as their only diagnosis. Participants were more likely to have only comorbid anxiety disorders than only comorbid depressive or somatoform disorders. Multiple regression analysis of continuous measures of symptoms revealed the strongest correlation of health anxiety with anxiety symptoms, and a weaker correlation with somatoform symptoms; in multiple regression analysis, there was no correlation between health anxiety and depressive symptoms. Our findings suggest that the entity of health anxiety (HC in DSM-IV and illness anxiety disorder in DSM-5) is a clinical syndrome distinct from other psychiatric disorders. Analysis of comorbidity patterns and continuous measures of symptoms suggest that its appropriate classification is with anxiety rather than somatoform or mood disorders. Copyright © 2016 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Distinct Neural Properties in the Low-Frequency Region of the Chicken Cochlear Nucleus Magnocellularis

PubMed Central

2017-01-01

Abstract Topography in the avian cochlear nucleus magnocellularis (NM) is represented as gradually increasing characteristic frequency (CF) along the caudolateral-to-rostromedial axis. In this study, we characterized the organization and cell biophysics of the caudolateral NM (NMc) in chickens (Gallus gallus). Examination of cellular and dendritic architecture first revealed that NMc contains small neurons and extensive dendritic processes, in contrast to adendritic, large neurons located more rostromedially. Individual dye-filling study further demonstrated that NMc is divided into two subregions, with NMc2 neurons having larger and more complex dendritic fields than NMc1. Axonal tract tracing studies confirmed that NMc1 and NMc2 neurons receive afferent inputs from the auditory nerve and the superior olivary nucleus, similar to the adendritic NM. However, the auditory axons synapse with NMc neurons via small bouton-like terminals, unlike the large end bulb synapses on adendritic NM neurons. Immunocytochemistry demonstrated that most NMc2 neurons express cholecystokinin but not calretinin, distinct from NMc1 and adendritic NM neurons that are cholecystokinin negative and mostly calretinin positive. Finally, whole-cell current clamp recordings revealed that NMc neurons require significantly lower threshold current for action potential generation than adendritic NM neurons. Moreover, in contrast to adendritic NM neurons that generate a single-onset action potential, NMc neurons generate multiple action potentials to suprathreshold sustained depolarization. Taken together, our data indicate that NMc contains multiple neuron types that are structurally, connectively, molecularly, and physiologically different from traditionally defined NM neurons, emphasizing specialized neural properties for processing low-frequency sounds. PMID:28413822

Structural or pigmentary? Origin of the distinctive white stripe on the blue wing of a Morpho butterfly.

PubMed

Yoshioka, Shinya; Kinoshita, Shuichi

2006-01-22

A few species of Morpho butterflies have a distinctive white stripe pattern on their structurally coloured blue wings. Since the colour pattern of a butterfly wing is formed as a mosaic of differently coloured scales, several questions naturally arise: are the microstructures the same between the blue and white scales? How is the distinctive whiteness produced, structurally or by means of pigmentation? To answer these questions, we have performed structural and optical investigations of the stripe pattern of a butterfly, Morpho cypris. It is found that besides the dorsal and ventral scale layers, the wing substrate also has the corresponding stripe pattern. Quantitative optical measurements and analysis using a simple model for the wing structure reveal the origin of the higher reflectance which makes the white stripe brighter.

Manifesting the Quantum World

NASA Astrophysics Data System (ADS)

Mohrhoff, Ulrich

2014-06-01

In resisting attempts to explain the unity of a whole in terms of a multiplicity of interacting parts, quantum mechanics calls for an explanatory concept that proceeds in the opposite direction: from unity to multiplicity. Being part of the Scientific Image of the world, the theory concerns the process by which (the physical aspect of) what Sellars called the Manifest Image of the world comes into being. This process consists in the progressive differentiation of an intrinsically undifferentiated entity. By entering into reflexive spatial relations, this entity gives rise to (i) what looks like a multiplicity of relata if the reflexive quality of the relations is not taken into account, and (ii) what looks like a substantial expanse if the spatial quality of the relations is reified. If there is a distinctly quantum domain, it is a non-spatial and non-temporal dimension across which the transition from the unity of this entity to the multiplicity of the world takes place. Instead of being constituents of the physical world, subatomic particles, atoms, and molecules are instrumental in its manifestation. These conclusions are based on the following interpretive principle and its more direct consequences: whenever the calculation of probabilities calls for the addition of amplitudes, the distinctions we make between the alternatives lack objective reality. Applied to alternatives involving distinctions between regions of space, this principle implies that, owing to the indefiniteness of positions, the spatiotemporal differentiation of the physical world is incomplete: the existence of a real-valued spatiotemporal background is an unrealistic idealization. This guarantees the existence of observables whose values are real per se, as against "real by virtue of being indicated by the values of observables that are real per se." Applied to alternatives involving distinctions between things, it implies that, intrinsically, all fundamental particles are numerically identical and thus identifiable with the aforementioned undifferentiated entity.

Leptospira interrogans causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells

PubMed Central

Sato, Hiromi

2017-01-01

Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability. Despite the burden in humans and animals, the pathogenic mechanisms of Leptospira infection remain to be elucidated. The pathogenic leptospires adhere to endothelial cells and permeabilize endothelial barriers in vivo and in vitro. In this study, human endothelial cells were infected with the pathogenic L. interrogans serovar Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate morphological changes and other distinctive phenotypes of host cell proteins by fluorescence microscopy. Among those analyzed, 17 proteins from five biological classes demonstrated distinctive phenotypes in morphology and/or signal intensity upon infection with Leptospira. The affected biological groups include: 1) extracellular matrix, 2) intercellular adhesion molecules and cell surface receptors, 3) intracellular proteins, 4) cell-cell junction proteins, and 5) a cytoskeletal protein. Infection with the pathogenic strain most profoundly disturbed the biological structures of adherens junctions (VE-cadherin and catenins) and actin filaments. Our data illuminate morphological disruptions and reduced signals of cell-cell junction proteins and filamentous actin in L. interrogans-infected endothelial cells. In addition, Leptospira infection, regardless of pathogenic status, influenced other host proteins belonging to multiple biological classes. Our data suggest that this zoonotic agent may damage endothelial cells via multiple cascades or pathways including endothelial barrier damage and inflammation, potentially leading to vascular hyperpermeability and severe illness in vivo. This work provides new insights into the pathophysiological mechanisms of Leptospira infection. PMID:28750011

Leptospira interrogans causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells.

PubMed

Sato, Hiromi; Coburn, Jenifer

2017-07-01

Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability. Despite the burden in humans and animals, the pathogenic mechanisms of Leptospira infection remain to be elucidated. The pathogenic leptospires adhere to endothelial cells and permeabilize endothelial barriers in vivo and in vitro. In this study, human endothelial cells were infected with the pathogenic L. interrogans serovar Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate morphological changes and other distinctive phenotypes of host cell proteins by fluorescence microscopy. Among those analyzed, 17 proteins from five biological classes demonstrated distinctive phenotypes in morphology and/or signal intensity upon infection with Leptospira. The affected biological groups include: 1) extracellular matrix, 2) intercellular adhesion molecules and cell surface receptors, 3) intracellular proteins, 4) cell-cell junction proteins, and 5) a cytoskeletal protein. Infection with the pathogenic strain most profoundly disturbed the biological structures of adherens junctions (VE-cadherin and catenins) and actin filaments. Our data illuminate morphological disruptions and reduced signals of cell-cell junction proteins and filamentous actin in L. interrogans-infected endothelial cells. In addition, Leptospira infection, regardless of pathogenic status, influenced other host proteins belonging to multiple biological classes. Our data suggest that this zoonotic agent may damage endothelial cells via multiple cascades or pathways including endothelial barrier damage and inflammation, potentially leading to vascular hyperpermeability and severe illness in vivo. This work provides new insights into the pathophysiological mechanisms of Leptospira infection.

NAViGaTing the Micronome – Using Multiple MicroRNA Prediction Databases to Identify Signalling Pathway-Associated MicroRNAs

PubMed Central

Shirdel, Elize A.; Xie, Wing; Mak, Tak W.; Jurisica, Igor

2011-01-01

Background MicroRNAs are a class of small RNAs known to regulate gene expression at the transcript level, the protein level, or both. Since microRNA binding is sequence-based but possibly structure-specific, work in this area has resulted in multiple databases storing predicted microRNA:target relationships computed using diverse algorithms. We integrate prediction databases, compare predictions to in vitro data, and use cross-database predictions to model the microRNA:transcript interactome – referred to as the micronome – to study microRNA involvement in well-known signalling pathways as well as associations with disease. We make this data freely available with a flexible user interface as our microRNA Data Integration Portal — mirDIP (http://ophid.utoronto.ca/mirDIP). Results mirDIP integrates prediction databases to elucidate accurate microRNA:target relationships. Using NAViGaTOR to produce interaction networks implicating microRNAs in literature-based, KEGG-based and Reactome-based pathways, we find these signalling pathway networks have significantly more microRNA involvement compared to chance (p<0.05), suggesting microRNAs co-target many genes in a given pathway. Further examination of the micronome shows two distinct classes of microRNAs; universe microRNAs, which are involved in many signalling pathways; and intra-pathway microRNAs, which target multiple genes within one signalling pathway. We find universe microRNAs to have more targets (p<0.0001), to be more studied (p<0.0002), and to have higher degree in the KEGG cancer pathway (p<0.0001), compared to intra-pathway microRNAs. Conclusions Our pathway-based analysis of mirDIP data suggests microRNAs are involved in intra-pathway signalling. We identify two distinct classes of microRNAs, suggesting a hierarchical organization of microRNAs co-targeting genes both within and between pathways, and implying differential involvement of universe and intra-pathway microRNAs at the disease level. PMID:21364759

Unraveling flp-11/flp-32 dichotomy in nematodes.

PubMed

Atkinson, Louise E; Miskelly, Iain R; Moffett, Christy L; McCoy, Ciaran J; Maule, Aaron G; Marks, Nikki J; Mousley, Angela

2016-10-01

FMRFamide-like peptide (FLP) signalling systems are core to nematode neuromuscular function. Novel drug discovery efforts associated with nematode FLP/FLP receptor biology are advanced through the accumulation of basic biological data that can reveal subtle complexities within the neuropeptidergic system. This study reports the characterisation of FMRFamide-like peptide encoding gene-11 (flp-11) and FMRFamide-like peptide encoding gene-32 (flp-32), two distinct flp genes which encode the analogous peptide, AMRN(A/S)LVRFamide, in multiple nematode species - the only known example of this phenomenon within the FLPergic system of nematodes. Using bioinformatics, in situ hybridisation, immunocytochemistry and behavioural assays we show that: (i) flp-11 and -32 are distinct flp genes expressed individually or in tandem across multiple nematode species, where they encode a highly similar peptide; (ii) flp-11 does not appear to be the most widely expressed flp in Caenorhabditis elegans; (iii) in species expressing both flp-11 and flp-32, flp-11 displays a conserved, restricted expression pattern across nematode clades and lifestyles; (iv) in species expressing both flp-11 and flp-32, flp-32 expression is more widespread and less conserved than flp-11; (v) in species expressing only flp-11, the flp-11 expression profile is more similar to the flp-32 profile observed in species expressing both; and (vi) FLP-11 peptides inhibit motor function in multiple nematode species. The biological significance and evolutionary origin of flp-11 and -32 peptide duplication remains unclear despite attempts to identify a common ancestor; this may become clearer as the availability of genomic data improves. This work provides insight into the complexity of the neuropeptidergic system in nematodes, and begins to examine how nematodes may compensate for structural neuronal simplicity. From a parasite control standpoint, this work underscores the importance of basic biological data, and has wider implications for the utility of C. elegans as a model for parasite neurobiology. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

A new zinc-1,3,5-benzenetricarboxylate framework integrated three distinct subunits (SBUs)

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

Xie, Yi-Ming, E-mail: ymxie@fjirsm.ac.cn

2013-06-01

A new metal-organic framework (MOF) [Zn₅(btc)₃(H₂O)₀.₅(O)₀.₅(DMA)₃]·1.75(DMA) (1; btc=1,3,5-benzenetricarboxylate; DMA=N,N´-dimethyl acetamide) has been solvothermally synthesized. Unusually, three distinct subunits (SBUs), [Zn₂(CO₂)₄(DMA)₂], [(μ₃-H₂O)Zn₃(CO₂)₆(DMA)] and [(µ₄-O)Zn₄(CO₂)₆(DMA)₂] are observed in 1 simultaneously. The integration of three distinct SBUs leads to an interesting Zn-btc framework materials with unusual structural topology. - Graphical abstract: Presented here is a new zinc-1,3,5-benzenetricarboxylate framework integrated three distinct subunits (SBUs). - Highlights: • A new zinc-1,3,5-benzenetricarboxylate framework has been synthesized. • Three distinct subunits (SBUs) are observed in 1 simultaneously. • The integration of three distinct SBUs leads to an unusual structural topology.

Comorbidity and ventricular and vascular structure and function in heart failure with preserved ejection fraction: a community-based study.

PubMed

Mohammed, Selma F; Borlaug, Barry A; Roger, Véronique L; Mirzoyev, Sultan A; Rodeheffer, Richard J; Chirinos, Julio A; Redfield, Margaret M

2012-11-01

Patients with heart failure and preserved ejection fraction (HFpEF) display increased adiposity and multiple comorbidities, factors that in themselves may influence cardiovascular structure and function. This has sparked debate as to whether HFpEF represents a distinct disease or an amalgamation of comorbidities. We hypothesized that fundamental cardiovascular structural and functional alterations are characteristic of HFpEF, even after accounting for body size and comorbidities. Comorbidity-adjusted cardiovascular structural and functional parameters scaled to independently generated and age-appropriate allometric powers were compared in community-based cohorts of HFpEF patients (n=386) and age/sex-matched healthy n=193 and hypertensive, n=386 controls. Within HFpEF patients, body size and concomitant comorbidity-adjusted cardiovascular structural and functional parameters and survival were compared in those with and without individual comorbidities. Among HFpEF patients, comorbidities (obesity, anemia, diabetes mellitus, and renal dysfunction) were each associated with unique clinical, structural, functional, and prognostic profiles. However, after accounting for age, sex, body size, and comorbidities, greater concentric hypertrophy, atrial enlargement and systolic, diastolic, and vascular dysfunction were consistently observed in HFpEF compared with age/sex-matched normotensive and hypertensive. Comorbidities influence ventricular-vascular properties and outcomes in HFpEF, yet fundamental disease-specific changes in cardiovascular structure and function underlie this disorder. These data support the search for mechanistically targeted therapies in this disease.

Structures of minute virus of mice replication initiator protein N-terminal domain: Insights into DNA nicking and origin binding

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

Tewary, Sunil K.; Liang, Lingfei; Lin, Zihan

Members of the Parvoviridae family all encode a non-structural protein 1 (NS1) that directs replication of single-stranded viral DNA, packages viral DNA into capsid, and serves as a potent transcriptional activator. Here we report the X-ray structure of the minute virus of mice (MVM) NS1 N-terminal domain at 1.45 Å resolution, showing that sites for dsDNA binding, ssDNA binding and cleavage, nuclear localization, and other functions are integrated on a canonical fold of the histidine-hydrophobic-histidine superfamily of nucleases, including elements specific for this Protoparvovirus but distinct from its Bocaparvovirus or Dependoparvovirus orthologs. High resolution structural analysis reveals a nickase activemore » site with an architecture that allows highly versatile metal ligand binding. The structures support a unified mechanism of replication origin recognition for homotelomeric and heterotelomeric parvoviruses, mediated by a basic-residue-rich hairpin and an adjacent helix in the initiator proteins and by tandem tetranucleotide motifs in the replication origins. - Highlights: • The structure of a parvovirus replication initiator protein has been determined; • The structure sheds light on mechanisms of ssDNA binding and cleavage; • The nickase active site is preconfigured for versatile metal ligand binding; • The binding site for the double-stranded replication origin DNA is identified; • A single domain integrates multiple functions in virus replication.« less

Socio-Cognitive Phenotypes Differentially Modulate Large-Scale Structural Covariance Networks.

PubMed

Valk, Sofie L; Bernhardt, Boris C; Böckler, Anne; Trautwein, Fynn-Mathis; Kanske, Philipp; Singer, Tania

2017-02-01

Functional neuroimaging studies have suggested the existence of 2 largely distinct social cognition networks, one for theory of mind (taking others' cognitive perspective) and another for empathy (sharing others' affective states). To address whether these networks can also be dissociated at the level of brain structure, we combined behavioral phenotyping across multiple socio-cognitive tasks with 3-Tesla MRI cortical thickness and structural covariance analysis in 270 healthy adults, recruited across 2 sites. Regional thickness mapping only provided partial support for divergent substrates, highlighting that individual differences in empathy relate to left insular-opercular thickness while no correlation between thickness and mentalizing scores was found. Conversely, structural covariance analysis showed clearly divergent network modulations by socio-cognitive and -affective phenotypes. Specifically, individual differences in theory of mind related to structural integration between temporo-parietal and dorsomedial prefrontal regions while empathy modulated the strength of dorsal anterior insula networks. Findings were robust across both recruitment sites, suggesting generalizability. At the level of structural network embedding, our study provides a double dissociation between empathy and mentalizing. Moreover, our findings suggest that structural substrates of higher-order social cognition are reflected rather in interregional networks than in the the local anatomical markup of specific regions per se. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Similar local order in disordered fluorite and aperiodic pyrochlore structures

DOE PAGES

Shamblin, Jacob; Tracy, Cameron; Palomares, Raul; ...

2017-10-01

A major challenge to understanding the response of materials to extreme environments (e.g., nuclear fuels/waste forms and fusion materials) is to unravel the processes by which a material can incorporate atomic-scale disorder, and at the same time, remain crystalline. While it has long been known that all condensed matter, even liquids and glasses, possess short-range order, the relation between fully-ordered, disordered, and aperiodic structures over multiple length scales is not well understood. For example, when defects are introduced (via pressure or irradiation) into materials adopting the pyrochlore structure, these complex oxides either disorder over specific crystallographic sites, remaining crystalline, ormore » become aperiodic. Here we present neutron total scattering results characterizing the irradiation response of two pyrochlores, one that is known to disorder (Er2Sn2O7) and the other to amorphize (Dy2Sn2O7) under ion irradiation. The results demonstrate that in both cases, the local pyrochlore structure is transformed into similar short range configurations that are best fit by the orthorhombic weberite structure, even though the two compositions have distinctly different structures, aperiodic vs. disordered-crystalline, at longer length scales. Thus, a material's resistance to amorphization may not depend primarily on local defect formation energies, but rather on the structure's compatibility with meso-scale modulations of the local order in a way that maintains long-range periodicity.« less

Genetic Diversity in Introduced Golden Mussel Populations Corresponds to Vector Activity

PubMed Central

Ghabooli, Sara; Zhan, Aibin; Sardiña, Paula; Paolucci, Esteban; Sylvester, Francisco; Perepelizin, Pablo V.; Briski, Elizabeta; Cristescu, Melania E.; MacIsaac, Hugh J.

2013-01-01

We explored possible links between vector activity and genetic diversity in introduced populations of Limnoperna fortunei by characterizing the genetic structure in native and introduced ranges in Asia and South America. We surveyed 24 populations: ten in Asia and 14 in South America using the mitochondrial cytochrome c oxidase subunit I (COI) gene, as well as eight polymorphic microsatellite markers. We performed population genetics and phylogenetic analyses to investigate population genetic structure across native and introduced regions. Introduced populations in Asia exhibit higher genetic diversity (H E = 0.667–0.746) than those in South America (H E = 0.519–0.575), suggesting higher introduction effort for the former populations. We observed pronounced geographical structuring in introduced regions, as indicated by both mitochondrial and nuclear markers based on multiple genetic analyses including pairwise ФST, F ST, Bayesian clustering method, and three-dimensional factorial correspondence analyses. Pairwise F ST values within both Asia (F ST = 0.017–0.126, P = 0.000–0.009) and South America (F ST = 0.004–0.107, P = 0.000–0.721) were lower than those between continents (F ST = 0.180–0.319, P = 0.000). Fine-scale genetic structuring was also apparent among introduced populations in both Asia and South America, suggesting either multiple introductions of distinct propagules or strong post-introduction selection and demographic stochasticity. Higher genetic diversity in Asia as compared to South America is likely due to more frequent propagule transfers associated with higher shipping activities between source and donor regions within Asia. This study suggests that the intensity of human-mediated introduction vectors influences patterns of genetic diversity in non-indigenous species. PMID:23533614

Complete structure of the polysaccharide from Streptococcus sanguis J22

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

Abeygunawardana, C.; Bush, C.A.; Cisar, J.O.

1990-01-09

The cell wall polysaccharides of certain oral streptococci such as Streptococcus sanguis strains 34 and J22, although immunologically distinct, act as receptors for the fimbrial lectins of Actinomyces viscosus T14V. The authors report the complete covalent structure of the polysaccharide from S. sanguis J22 which is composed of a heptasaccharide subunit linked by phosphodiester bonds. The repeating subunit, which contains {alpha}-GalNAc, {alpha}-rhamnose, {beta}-rhamnose, {beta}-glucose, and {beta}-galactose all in the pyranoside form and {beta}-galactofuranose, is compared with the previously published structure of the polysaccharide from strain 34. The structure has been determined almost exclusively by high-resolution nuclear magnetic resonance methods. Themore » {sup 1}H and {sup 13}C NMR spectra of the polysaccharides from both strains 34 and J22 have been completely assigned. The stereochemistry of pyranosides was assigned from J{sub H-H} values determined from phase-sensitive COSY spectra, and acetamido sugars were assigned by correlation of the resonances of the amide {sup 1}H with the sugar ring protons. The {sup 13}C spectra were assigned by {sup 1}H-detected multiple-quantum correlation (HMQC) spectra, and the assignments were confirmed by {sup 1}H-detected multiple-bond correlation (HMBC) spectra. The positions of the glycosidic linkages were assigned by detection of three-bond {sup 1}H-{sup 13}C correlation across the glycosidic linkage in the HMBC spectra. The positions of the phosphodiester linkages were determined by splittings observed in the {sup 13}C resonances due to {sup 31}P coupling and also by {sup 1}H-detected {sup 31}P correlation spectroscopy.« less

Community structure and diversity of scavenging amphipods from bathyal to hadal depths in three South Pacific Trenches

NASA Astrophysics Data System (ADS)

Lacey, Nichola C.; Rowden, Ashley A.; Clark, Malcolm R.; Kilgallen, Niamh M.; Linley, Thomas; Mayor, Dan J.; Jamieson, Alan J.

2016-05-01

There are few biological datasets that span large bathymetric ranges with sufficient resolution to identify trends across the abyssal and hadal transition zone, particularly over multiple trenches. Here, scavenging Amphipoda were collected from three trenches in the South Pacific Ocean at bathyal to hadal depths. Diversity and community structure were examined from stations within the Kermadec Trench (1490-9908 m) and New Hebrides Trench (2000-6948 m) and additional data were included from the South Fiji Basin (4000 m) and Peru-Chile Trench (4602-8074 m). The hadal community structure of the Kermadec and New Hebrides trenches were distinct from the surrounding abyssal and bathyal depths and correlated to hydrostatic pressure and POC flux. Low POC flux in the New Hebrides Trench and South Fiji Basin best explained the dissimilarity in abyssal community structure from those of the disparate Kermadec and Peru-Chile trenches. POC flux also best explained patterns in hadal community structure with the Kermadec and New Hebrides Trench communities showing greater similarity to each other than to the eutrophic Peru-Chile Trench. Hydrostatic pressure was the strongest driver of intra-trench assemblage composition in all trench environments. A unimodal pattern of species diversity, peaking between 4000 and 5000 m, was best explained by hydrostatic pressure and temperature.

Topological Constraints and Their Conformational Entropic Penalties on RNA Folds.

PubMed

Mak, Chi H; Phan, Ethan N H

2018-05-08

Functional RNAs can fold into intricate structures using a number of different secondary and tertiary structural motifs. Many factors contribute to the overall free energy of the target fold. This study aims at quantifying the entropic costs coming from the loss of conformational freedom when the sugar-phosphate backbone is subjected to constraints imposed by secondary and tertiary contacts. Motivated by insights from topology theory, we design a diagrammatic scheme to represent different types of RNA structures so that constraints associated with a folded structure may be segregated into mutually independent subsets, enabling the total conformational entropy loss to be easily calculated as a sum of independent terms. We used high-throughput Monte Carlo simulations to simulate large ensembles of single-stranded RNA sequences in solution to validate the assumptions behind our diagrammatic scheme, examining the entropic costs for hairpin initiation and formation of many multiway junctions. Our diagrammatic scheme aids in the factorization of secondary/tertiary constraints into distinct topological classes and facilitates the discovery of interrelationships among multiple constraints on RNA folds. This perspective, which to our knowledge is novel, leads to useful insights into the inner workings of some functional RNA sequences, demonstrating how they might operate by transforming their structures among different topological classes. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Genetic diversity of Diaphorina citri and its endosymbionts across east and south-east Asia.

PubMed

Wang, Yanjing; Xu, Changbao; Tian, Mingyi; Deng, Xiaoling; Cen, Yijing; He, Yurong

2017-10-01

Diaphorina citri is the vector of 'Candidatus Liberibacter asiaticus', the most widespread pathogen associated huanglongbing, the most serious disease of citrus. To enhance our understanding of the distribution and origin of the psyllid, we investigated the genetic diversity and population structures of 24 populations in Asia and one from Florida based on the mtCOI gene. Simultaneously, genetic diversity and population structures of the primary endosymbiont (P-endosymbiont) 'Candidatus Carsonella ruddii' and secondary endosymbiont (S-endosymbiont) 'Candidatus Profftella armatura' of D. citri were determined with the housekeeping genes. AMOVA analysis indicated that populations of D. citri and its endosymbionts in east and south-east Asia were genetically distinct from populations in Pakistan and Florida. Furthermore, P-endosymbiont populations displayed a strong geographical structure across east and south-east Asia, while low genetic diversity indicated the absence of genetic structure among the populations of D. citri and its S-endosymbiont across these regions. The 'Ca. C. ruddii' is more diverse and structured than the D. citri and the 'Ca. P. armatura' across east and south-east Asia. Multiple introductions of the psyllid have occurred in China. Management application for controlling the pest is proposed based on the genetic information of D. citri and its endosymbionts. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

X-ray structure of the dopamine transporter in complex with tricyclic antidepressant

PubMed Central

Penmatsa, Aravind; Wang, Kevin H.; Gouaux, Eric

2013-01-01

Antidepressants targeting Na+/Cl−-coupled neurotransmitter uptake define a major therapeutic strategy to treat clinical depression and neuropathic pain. However, identifying the molecular interactions that underlie the pharmacological activity of these transport inhibitors and thus the mechanism by which the inhibitors lead to increased synaptic neurotransmitter levels has proven elusive. Here we present the crystal structure of the Drosophila melanogaster dopamine transporter (dDAT) at 3.0 Å resolution bound to the tricyclic antidepressant nortriptyline. The transporter is locked in an outward-open conformation with nortriptyline wedged between TMs1/6 and 3/8, blocking the transporter from binding substrate and from isomerizing to an inward facing conformation. While the overall structure of dDAT is similar to that of its prokaryotic relative LeuT, there are multiple distinctions that include a kink in TM12 halfway across the membrane bilayer, a latch-like C-terminal helix that caps the cytoplasmic gate, and a cholesterol molecule wedged within a groove formed by TMs 1a, 5 and 7. Taken together, the dDAT structure reveals the molecular basis for antidepressant action on sodium-coupled neurotransmitter symporters and illuminates critical elements of eukaryotic transporter structure and modulation by lipids, thus expanding our understanding of mechanism and regulation of neurotransmitter uptake at chemical synapses. PMID:24037379

Distinct Functional Roles of β-Tubulin Isotypes in Microtubule Arrays of Tetrahymena thermophila, a Model Single-Celled Organism

PubMed Central

Pucciarelli, Sandra; Ballarini, Patrizia; Sparvoli, Daniela; Barchetta, Sabrina; Yu, Ting; Detrich, H. William; Miceli, Cristina

2012-01-01

Background The multi-tubulin hypothesis proposes that each tubulin isotype performs a unique role, or subset of roles, in the universe of microtubule function(s). To test this hypothesis, we are investigating the functions of the recently discovered, noncanonical β-like tubulins (BLTs) of the ciliate, Tetrahymena thermophila. Tetrahymena forms 17 distinct microtubular structures whose assembly had been thought to be based on single α- and β-isotypes. However, completion of the macronuclear genome sequence of Tetrahymena demonstrated that this ciliate possessed a β-tubulin multigene family: two synonymous genes (BTU1 and BTU2) encode the canonical β-tubulin, BTU2, and six genes (BLT1-6) yield five divergent β-tubulin isotypes. In this report, we examine the structural features and functions of two of the BLTs (BLT1 and BLT4) and compare them to those of BTU2. Methodology/Principal Findings With respect to BTU2, BLT1 and BLT4 had multiple sequence substitutions in their GTP-binding sites, in their interaction surfaces, and in their microtubule-targeting motifs, which together suggest that they have specialized functions. To assess the roles of these tubulins in vivo, we transformed Tetrahymena with expression vectors that direct the synthesis of GFP-tagged versions of the isotypes. We show that GFP-BLT1 and GFP-BLT4 were not detectable in somatic cilia and basal bodies, whereas GFP-BTU2 strongly labeled these structures. During cell division, GFP-BLT1 and GFP-BLT4, but not GFP-BTU2, were incorporated into the microtubule arrays of the macronucleus and into the mitotic apparatus of the micronucleus. GFP-BLT1 also participated in formation of the microtubules of the meiotic apparatus of the micronucleus during conjugation. Partitioning of the isotypes between nuclear and ciliary microtubules was confirmed biochemically. Conclusion/Significance We conclude that Tetrahymena uses a family of distinct β-tubulin isotypes to construct subsets of functionally different microtubules, a result that provides strong support for the multi-tubulin hypothesis. PMID:22745812

Hydraulic characterization of volcanic rocks in Pahute Mesa using an integrated analysis of 16 multiple-well aquifer tests, Nevada National Security Site, 2009–14

USGS Publications Warehouse

Garcia, C. Amanda; Jackson, Tracie R.; Halford, Keith J.; Sweetkind, Donald S.; Damar, Nancy A.; Fenelon, Joseph M.; Reiner, Steven R.

2017-01-20

An improved understanding of groundwater flow and radionuclide migration downgradient from underground nuclear-testing areas at Pahute Mesa, Nevada National Security Site, requires accurate subsurface hydraulic characterization. To improve conceptual models of flow and transport in the complex hydrogeologic system beneath Pahute Mesa, the U.S. Geological Survey characterized bulk hydraulic properties of volcanic rocks using an integrated analysis of 16 multiple-well aquifer tests. Single-well aquifer-test analyses provided transmissivity estimates at pumped wells. Transmissivity estimates ranged from less than 1 to about 100,000 square feet per day in Pahute Mesa and the vicinity. Drawdown from multiple-well aquifer testing was estimated and distinguished from natural fluctuations in more than 200 pumping and observation wells using analytical water-level models. Drawdown was detected at distances greater than 3 miles from pumping wells and propagated across hydrostratigraphic units and major structures, indicating that neither faults nor structural blocks noticeably impede or divert groundwater flow in the study area.Consistent hydraulic properties were estimated by simultaneously interpreting drawdown from the 16 multiple-well aquifer tests with an integrated groundwater-flow model composed of 11 well-site models—1 for each aquifer test site. Hydraulic properties were distributed across volcanic rocks with the Phase II Pahute Mesa-Oasis Valley Hydrostratigraphic Framework Model. Estimated hydraulic-conductivity distributions spanned more than two orders of magnitude in hydrostratigraphic units. Overlapping hydraulic conductivity ranges among units indicated that most Phase II Hydrostratigraphic Framework Model units were not hydraulically distinct. Simulated total transmissivity ranged from 1,600 to 68,000 square feet per day for all pumping wells analyzed. High-transmissivity zones exceeding 10,000 square feet per day exist near caldera margins and extend along the northern and eastern Pahute Mesa study area and near the southwestern edge of the study area. The estimated hydraulic-property distributions and observed hydraulic connections among geologic structures improved the characterization and representation of groundwater flow at Pahute Mesa.

Novel Insights and Therapeutics in Multiple Sclerosis.

PubMed

Wagner, Catriona A; Goverman, Joan M

2015-01-01

The last twelve years have witnessed the development of new therapies for relapsing-remitting multiple sclerosis that demonstrate increased efficacy relative to previous therapies. Many of these new drugs target the inflammatory phase of disease by manipulating different aspects of the immune system. While these new treatments are promising, the development of therapies for patients with progressive multiple sclerosis remains a significant challenge. We discuss the distinct mechanisms that may contribute to these two types of multiple sclerosis and the implications of these differences in the development of new therapeutic targets for this debilitating disease.

Intrahaplotypic Variants Differentiate Complex Linkage Disequilibrium within Human MHC Haplotypes

PubMed Central

Lam, Tze Hau; Tay, Matthew Zirui; Wang, Bei; Xiao, Ziwei; Ren, Ee Chee

2015-01-01

Distinct regions of long-range genetic fixation in the human MHC region, known as conserved extended haplotypes (CEHs), possess unique genomic characteristics and are strongly associated with numerous diseases. While CEHs appear to be homogeneous by SNP analysis, the nature of fine variations within their genomic structure is unknown. Using multiple, MHC-homozygous cell lines, we demonstrate extensive sequence conservation in two common Asian MHC haplotypes: A33-B58-DR3 and A2-B46-DR9. However, characterization of phase-resolved MHC haplotypes revealed unique intra-CEH patterns of variation and uncovered 127 single nucleotide variants (SNVs) which are missing from public databases. We further show that the strong linkage disequilibrium structure within the human MHC that typically confounds precise identification of genetic features can be resolved using intra-CEH variants, as evidenced by rs3129063 and rs448489, which affect expression of ZFP57, a gene important in methylation and epigenetic regulation. This study demonstrates an improved strategy that can be used towards genetic dissection of diseases. PMID:26593880

Genomewide analysis of Drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation

PubMed Central

Westholm, Jakub O.; Miura, Pedro; Olson, Sara; Shenker, Sol; Joseph, Brian; Sanfilippo, Piero; Celniker, Susan E.; Graveley, Brenton R.; Lai, Eric C.

2014-01-01

Circularization was recently recognized to broadly expand transcriptome complexity. Here, we exploit massive Drosophila total RNA-sequencing data, >5 billion paired-end reads from >100 libraries covering diverse developmental stages, tissues and cultured cells, to rigorously annotate >2500 fruitfly circular RNAs. These mostly derive from back-splicing of protein-coding genes and lack poly(A) tails, and circularization of hundreds of genes is conserved across multiple Drosophila species. We elucidate structural and sequence properties of Drosophila circular RNAs, which exhibit commonalities and distinctions from mammalian circles. Notably, Drosophila circular RNAs harbor >1000 well-conserved canonical miRNA seed matches, especially within coding regions, and coding conserved miRNA sites reside preferentially within circularized exons. Finally, we analyze the developmental and tissue specificity of circular RNAs, and note their preferred derivation from neural genes and enhanced accumulation in neural tissues. Interestingly, circular isoforms increase dramatically relative to linear isoforms during CNS aging, and constitute a novel aging biomarker. PMID:25544350

Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs.

PubMed

Jabłońska-Trypuć, Agata; Matejczyk, Marzena; Rosochacki, Stanisław

2016-01-01

The main group of enzymes responsible for the collagen and other protein degradation in extracellular matrix (ECM) are matrix metalloproteinases (MMPs). Collagen is the main structural component of connective tissue and its degradation is a very important process in the development, morphogenesis, tissue remodeling, and repair. Typical structure of MMPs consists of several distinct domains. MMP family can be divided into six groups: collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs, and other non-classified MMPs. MMPs and their inhibitors have multiple biological functions in all stages of cancer development: from initiation to outgrowth of clinically relevant metastases and likewise in apoptosis and angiogenesis. MMPs and their inhibitors are extensively examined as potential anticancer drugs. MMP inhibitors can be divided into two main groups: synthetic and natural inhibitors. Selected synthetic inhibitors are in clinical trials on humans, e.g. synthetic peptides, non-peptidic molecules, chemically modified tetracyclines, and bisphosphonates. Natural MMP inhibitors are mainly isoflavonoids and shark cartilage.

The Centrosome and Its Duplication Cycle

PubMed Central

Fu, Jingyan; Hagan, Iain M.; Glover, David M.

2015-01-01

The centrosome was discovered in the late 19th century when mitosis was first described. Long recognized as a key organelle of the spindle pole, its core component, the centriole, was realized more than 50 or so years later also to comprise the basal body of the cilium. Here, we chart the more recent acquisition of a molecular understanding of centrosome structure and function. The strategies for gaining such knowledge were quickly developed in the yeasts to decipher the structure and function of their distinctive spindle pole bodies. Only within the past decade have studies with model eukaryotes and cultured cells brought a similar degree of sophistication to our understanding of the centrosome duplication cycle and the multiple roles of this organelle and its component parts in cell division and signaling. Now as we begin to understand these functions in the context of development, the way is being opened up for studies of the roles of centrosomes in human disease. PMID:25646378

Structural dynamics of ribosome subunit association studied by mixing-spraying time-resolved cryo-EM

PubMed Central

Chen, Bo; Kaledhonkar, Sandip; Sun, Ming; Shen, Bingxin; Lu, Zonghuan; Barnard, David; Lu, Toh-Ming; Gonzalez, Ruben L.; Frank, Joachim

2015-01-01

Ribosomal subunit association is a key checkpoint in translation initiation, but its structural dynamics are poorly understood. Here, we used a recently developed mixing-spraying, time-resolved, cryogenic electron microscopy (cryo-EM) method to study ribosomal subunit association in the sub-second time range. We have improved this method and increased the cryo-EM data yield by tenfold. Pre-equilibrium states of the association reaction were captured by reacting the mixture of ribosomal subunits for 60 ms and 140 ms. We also identified three distinct ribosome conformations in the associated ribosomes. The observed proportions of these conformations are the same in these two time points, suggesting that ribosomes equilibrate among the three conformations within less than 60 ms upon formation. Our results demonstrate that the mixing-spraying method can capture multiple states of macromolecules during a sub-second reaction. Other fast processes, such as translation initiation, decoding and ribosome recycling, are amenable to study with this method. PMID:26004440

Portal protein functions akin to a DNA-sensor that couples genome-packaging to icosahedral capsid maturation

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

Lokareddy, Ravi K.; Sankhala, Rajeshwer S.; Roy, Ankoor

Tailed bacteriophages and herpesviruses assemble infectious particles via an empty precursor capsid (or ‘procapsid’) built by multiple copies of coat and scaffolding protein and by one dodecameric portal protein. Genome packaging triggers rearrangement of the coat protein and release of scaffolding protein, resulting in dramatic procapsid lattice expansion. Here, we provide structural evidence that the portal protein of the bacteriophage P22 exists in two distinct dodecameric conformations: an asymmetric assembly in the procapsid (PC-portal) that is competent for high affinity binding to the large terminase packaging protein, and a symmetric ring in the mature virion (MV-portal) that has negligible affinitymore » for the packaging motor. Modelling studies indicate the structure of PC-portal is incompatible with DNA coaxially spooled around the portal vertex, suggesting that newly packaged DNA triggers the switch from PC- to MV-conformation. Thus, we propose the signal for termination of ‘Headful Packaging’ is a DNA-dependent symmetrization of portal protein.« less

Three-dimensional shape transformations of hydrogel sheets induced by small-scale modulation of internal stresses

NASA Astrophysics Data System (ADS)

Wu, Zi Liang; Moshe, Michael; Greener, Jesse; Therien-Aubin, Heloise; Nie, Zhihong; Sharon, Eran; Kumacheva, Eugenia

2013-03-01

Although Nature has always been a common source of inspiration in the development of artificial materials, only recently has the ability of man-made materials to produce complex three-dimensional (3D) structures from two-dimensional sheets been explored. Here we present a new approach to the self-shaping of soft matter that mimics fibrous plant tissues by exploiting small-scale variations in the internal stresses to form three-dimensional morphologies. We design single-layer hydrogel sheets with chemically distinct, fibre-like regions that exhibit differential shrinkage and elastic moduli under the application of external stimulus. Using a planar-to-helical three-dimensional shape transformation as an example, we explore the relation between the internal architecture of the sheets and their transition to cylindrical and conical helices with specific structural characteristics. The ability to engineer multiple three-dimensional shape transformations determined by small-scale patterns in a hydrogel sheet represents a promising step in the development of programmable soft matter.

Using in vivo probabilistic tractography to reveal two segregated dorsal ‘language-cognitive’ pathways in the human brain☆

PubMed Central

Cloutman, Lauren L.; Binney, Richard J.; Morris, David M.; Parker, Geoffrey J.M.; Lambon Ralph, Matthew A.

2013-01-01

Primate studies have recently identified the dorsal stream as constituting multiple dissociable pathways associated with a range of specialized cognitive functions. To elucidate the nature and number of dorsal pathways in the human brain, the current study utilized in vivo probabilistic tractography to map the structural connectivity associated with subdivisions of the left supramarginal gyrus (SMG). The left SMG is a prominent region within the dorsal stream, which has recently been parcellated into five structurally-distinct regions which possess a dorsal–ventral (and rostral-caudal) organisation, postulated to reflect areas of functional specialisation. The connectivity patterns reveal a dissociation of the arcuate fasciculus into at least two segregated pathways connecting frontal-parietal-temporal regions. Specifically, the connectivity of the inferior SMG, implicated as an acoustic-motor speech interface, is carried by an inner/ventro-dorsal arc of fibres, whilst the pathways of the posterior superior SMG, implicated in object use and cognitive control, forms a parallel outer/dorso-dorsal crescent. PMID:23937853