Sample records for native cellular context

  1. RNA Imaging with Multiplexed Error Robust Fluorescence in situ Hybridization

    PubMed Central

    Moffitt, Jeffrey R.; Zhuang, Xiaowei

    2016-01-01

    Quantitative measurements of both the copy number and spatial distribution of large fractions of the transcriptome in single-cells could revolutionize our understanding of a variety of cellular and tissue behaviors in both healthy and diseased states. Single-molecule Fluorescence In Situ Hybridization (smFISH)—an approach where individual RNAs are labeled with fluorescent probes and imaged in their native cellular and tissue context—provides both the copy number and spatial context of RNAs but has been limited in the number of RNA species that can be measured simultaneously. Here we describe Multiplexed Error Robust Fluorescence In Situ Hybridization (MERFISH), a massively parallelized form of smFISH that can image and identify hundreds to thousands of different RNA species simultaneously with high accuracy in individual cells in their native spatial context. We provide detailed protocols on all aspects of MERFISH, including probe design, data collection, and data analysis to allow interested laboratories to perform MERFISH measurements themselves. PMID:27241748

  2. Physiological enzymology: The next frontier in understanding protein structure and function at the cellular level.

    PubMed

    Lee, Irene; Berdis, Anthony J

    2016-01-01

    Historically, the study of proteins has relied heavily on characterizing the activity of a single purified protein isolated from other cellular components. This classic approach allowed scientists to unambiguously define the intrinsic kinetic and chemical properties of that protein. The ultimate hope was to extrapolate this information toward understanding how the enzyme or receptor behaves within its native cellular context. These types of detailed in vitro analyses were necessary to reduce the innate complexities of measuring the singular activity and biochemical properties of a specific enzyme without interference from other enzymes and potential competing substrates. However, recent developments in fields encompassing cell biology, molecular imaging, and chemical biology now provide the unique chemical tools and instrumentation to study protein structure, function, and regulation in their native cellular environment. These advancements provide the foundation for a new field, coined physiological enzymology, which quantifies the function and regulation of enzymes and proteins at the cellular level. In this Special Edition, we explore the area of Physiological Enzymology and Protein Function through a series of review articles that focus on the tools and techniques used to measure the cellular activity of proteins inside living cells. This article is part of a Special Issue entitled: Physiological Enzymology and Protein Functions. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Photocrosslinking approaches to interactome mapping

    PubMed Central

    Pham, Nam D.; Parker, Randy B.; Kohler, Jennifer J.

    2012-01-01

    Photocrosslinking approaches can be used to map interactome networks within the context of living cells. Photocrosslinking methods rely on use of metabolic engineering or genetic code expansion to incorporate photocrosslinking analogs of amino acids or sugars into cellular biomolecules. Immunological and mass spectrometry techniques are used to analyze crosslinked complexes, thereby defining specific interactomes. Because photocrosslinking can be conducted in native, cellular settings, it can be used to define context-dependent interactions. Photocrosslinking methods are also ideally suited for determining interactome dynamics, mapping interaction interfaces, and identifying transient interactions in which intrinsically disordered proteins and glycoproteins engage. Here we discuss the application of cell-based photocrosslinking to the study of specific problems in immune cell signaling, transcription, membrane protein dynamics, nucleocytoplasmic transport, and chaperone-assisted protein folding. PMID:23149092

  4. Cellular Electron Cryotomography: Toward Structural Biology In Situ.

    PubMed

    Oikonomou, Catherine M; Jensen, Grant J

    2017-06-20

    Electron cryotomography (ECT) provides three-dimensional views of macromolecular complexes inside cells in a native frozen-hydrated state. Over the last two decades, ECT has revealed the ultrastructure of cells in unprecedented detail. It has also allowed us to visualize the structures of macromolecular machines in their native context inside intact cells. In many cases, such machines cannot be purified intact for in vitro study. In other cases, the function of a structure is lost outside the cell, so that the mechanism can be understood only by observation in situ. In this review, we describe the technique and its history and provide examples of its power when applied to cell biology. We also discuss the integration of ECT with other techniques, including lower-resolution fluorescence imaging and higher-resolution atomic structure determination, to cover the full scale of cellular processes.

  5. Towards native-state imaging in biological context in the electron microscope

    PubMed Central

    Weston, Anne E.; Armer, Hannah E. J.

    2009-01-01

    Modern cell biology is reliant on light and fluorescence microscopy for analysis of cells, tissues and protein localisation. However, these powerful techniques are ultimately limited in resolution by the wavelength of light. Electron microscopes offer much greater resolution due to the shorter effective wavelength of electrons, allowing direct imaging of sub-cellular architecture. The harsh environment of the electron microscope chamber and the properties of the electron beam have led to complex chemical and mechanical preparation techniques, which distance biological samples from their native state and complicate data interpretation. Here we describe recent advances in sample preparation and instrumentation, which push the boundaries of high-resolution imaging. Cryopreparation, cryoelectron microscopy and environmental scanning electron microscopy strive to image samples in near native state. Advances in correlative microscopy and markers enable high-resolution localisation of proteins. Innovation in microscope design has pushed the boundaries of resolution to atomic scale, whilst automatic acquisition of high-resolution electron microscopy data through large volumes is finally able to place ultrastructure in biological context. PMID:19916039

  6. A scalable strategy for high-throughput GFP tagging of endogenous human proteins.

    PubMed

    Leonetti, Manuel D; Sekine, Sayaka; Kamiyama, Daichi; Weissman, Jonathan S; Huang, Bo

    2016-06-21

    A central challenge of the postgenomic era is to comprehensively characterize the cellular role of the ∼20,000 proteins encoded in the human genome. To systematically study protein function in a native cellular background, libraries of human cell lines expressing proteins tagged with a functional sequence at their endogenous loci would be very valuable. Here, using electroporation of Cas9 nuclease/single-guide RNA ribonucleoproteins and taking advantage of a split-GFP system, we describe a scalable method for the robust, scarless, and specific tagging of endogenous human genes with GFP. Our approach requires no molecular cloning and allows a large number of cell lines to be processed in parallel. We demonstrate the scalability of our method by targeting 48 human genes and show that the resulting GFP fluorescence correlates with protein expression levels. We next present how our protocols can be easily adapted for the tagging of a given target with GFP repeats, critically enabling the study of low-abundance proteins. Finally, we show that our GFP tagging approach allows the biochemical isolation of native protein complexes for proteomic studies. Taken together, our results pave the way for the large-scale generation of endogenously tagged human cell lines for the proteome-wide analysis of protein localization and interaction networks in a native cellular context.

  7. Spatial reconstruction of single-cell gene expression

    PubMed Central

    Satija, Rahul; Farrell, Jeffrey A.; Gennert, David; Schier, Alexander F.; Regev, Aviv

    2015-01-01

    Spatial localization is a key determinant of cellular fate and behavior, but spatial RNA assays traditionally rely on staining for a limited number of RNA species. In contrast, single-cell RNA-seq allows for deep profiling of cellular gene expression, but established methods separate cells from their native spatial context. Here we present Seurat, a computational strategy to infer cellular localization by integrating single-cell RNA-seq data with in situ RNA patterns. We applied Seurat to spatially map 851 single cells from dissociated zebrafish (Danio rerio) embryos, inferring a transcriptome-wide map of spatial patterning. We confirmed Seurat’s accuracy using several experimental approaches, and used it to identify a set of archetypal expression patterns and spatial markers. Additionally, Seurat correctly localizes rare subpopulations, accurately mapping both spatially restricted and scattered groups. Seurat will be applicable to mapping cellular localization within complex patterned tissues in diverse systems. PMID:25867923

  8. Crowding in Cellular Environments at an Atomistic Level from Computer Simulations

    PubMed Central

    2017-01-01

    The effects of crowding in biological environments on biomolecular structure, dynamics, and function remain not well understood. Computer simulations of atomistic models of concentrated peptide and protein systems at different levels of complexity are beginning to provide new insights. Crowding, weak interactions with other macromolecules and metabolites, and altered solvent properties within cellular environments appear to remodel the energy landscape of peptides and proteins in significant ways including the possibility of native state destabilization. Crowding is also seen to affect dynamic properties, both conformational dynamics and diffusional properties of macromolecules. Recent simulations that address these questions are reviewed here and discussed in the context of relevant experiments. PMID:28666087

  9. Stabilizing the Native Trimer of HIV-1 Env by Destabilizing the Heterodimeric Interface of the gp41 Postfusion Six-Helix Bundle

    PubMed Central

    Kesavardhana, Sannula

    2014-01-01

    ABSTRACT The HIV-1 envelope glycoprotein (Env) is a trimer of gp120-gp41 heterodimers and is essential for viral entry. The gp41 subunit in native, prefusion trimeric Env exists in a metastable conformation and attains a stable six-helix bundle (6-HB) conformation comprised of a trimer of N-heptad repeat (NHR) and C-heptad repeat (CHR) heterodimers, that drives the fusion of viral and cellular membranes. We attempted to stabilize native Env trimers by incorporation of mutations at the NHR-CHR interface that disrupt the postfusion 6-HB of gp41. The mutations V570D and I573D stabilize native Env of the HIV-1 JRFL strain and occlude nonneutralizing epitopes to a greater extent than the previously identified I559P mutation that is at the interface of the NHR trimers in the 6-HB. The mutations prevent soluble-CD4 (sCD4)-induced gp120 shedding and 6-HB formation. In the context of cell surface-expressed JRFL Env, introduction of a previously reported additional disulfide between residues A501 and T605 perturbs the native conformation, though this effect is partially alleviated by furin coexpression. The data suggest that positions 570 and 573 are surface proximal in native Env and that the NHR homotrimeric coiled coil in native Env terminates before or close to residue 573. Aspartic acid substitutions at these positions stabilize native trimers through destabilization of the postfusion 6-HB conformation. These mutations can be used to stabilize Env in a DNA vaccine format. IMPORTANCE The major protein on the surface of HIV-1 is the envelope (Env) glycoprotein. Env is a trimer of gp120-gp41 heterodimers. gp120 is involved in receptor/coreceptor binding and gp41 in the fusion of viral and cellular membranes. Like many other viral fusion proteins, the gp41 subunit in native trimeric Env exists in a metastable conformation. gp41 readily forms a stable six-helix bundle (6-HB) conformation comprised of a trimer of N-heptad repeat (NHR) and C-heptad repeat (CHR) heterodimers that drives fusion of viral and cellular membranes. While it is expected that native Env is a good immunogen, its metastability results in exposure of immunodominant nonneutralizing epitopes. In the present study, we stabilize native Env trimers by incorporation of a number of different mutations at the NHR-CHR interface that disrupt the postfusion 6-HB of gp41. The stabilized constructs described here can be incorporated into DNA vaccine candidates. PMID:24920800

  10. Spatial reconstruction of single-cell gene expression data.

    PubMed

    Satija, Rahul; Farrell, Jeffrey A; Gennert, David; Schier, Alexander F; Regev, Aviv

    2015-05-01

    Spatial localization is a key determinant of cellular fate and behavior, but methods for spatially resolved, transcriptome-wide gene expression profiling across complex tissues are lacking. RNA staining methods assay only a small number of transcripts, whereas single-cell RNA-seq, which measures global gene expression, separates cells from their native spatial context. Here we present Seurat, a computational strategy to infer cellular localization by integrating single-cell RNA-seq data with in situ RNA patterns. We applied Seurat to spatially map 851 single cells from dissociated zebrafish (Danio rerio) embryos and generated a transcriptome-wide map of spatial patterning. We confirmed Seurat's accuracy using several experimental approaches, then used the strategy to identify a set of archetypal expression patterns and spatial markers. Seurat correctly localizes rare subpopulations, accurately mapping both spatially restricted and scattered groups. Seurat will be applicable to mapping cellular localization within complex patterned tissues in diverse systems.

  11. Rearrangement of Upstream Sequences of the hTERT Gene During Cellular Immortalization

    PubMed Central

    Zhao, Yuanjun; Wang, Shuwen; Popova, Evgenya Y.; Grigoryev, Sergei A.; Zhu, Jiyue

    2010-01-01

    Telomerase expression, resulting from transcriptional activation of the hTERT gene, allows cells to acquire indefinite proliferative potential during cellular immortalization and tumorigenesis. However, mechanisms of hTERT gene activation in many immortal cell lines and cancer cells are poorly understood. Here, we report our studies on hTERT activation using genetically related pairs of telomerase-negative (Tel−) and -positive (Tel+) fibroblast lines. First, whereas transiently transfected plasmid reporters did not recapitulate the endogenous hTERT promoter, the promoter in chromosomally integrated bacterial artificial chromosome (BAC) reporters was activated in a subset of Tel+ cells, indicating that activation of the hTERT promoter required native chromatin context and/or distal regulatory elements. Second, the hTERT gene, located near the telomere of chromosome 5p, was translocated in all three Tel+ cell lines but not in their parental pre-crisis cells and Tel− immortal siblings. The breakage points were mapped to regions upstream of the hTERT promoter, indicating that the hTERT gene was the target of these chromosomal rearrangements. In two Tel+ cell lines, translocation of the endogenous hTERT gene appeared to be the major mechanism of its activation as the activity of hTERT promoter in many chromosomally integrated BAC reporters, with intact upstream and downstream neighboring loci, remained relatively low. Therefore, our results suggest that rearrangement of upstream sequences is an important new mechanism of hTERT promoter activation during cellular immortalization. The chromosomal rearrangements likely occurred during cellular crisis and facilitated by telomere dysfunction. Such translocations allowed the hTERT promoter to escape from the native condensed chromatin environment. PMID:19672873

  12. Lateral diffusion and signaling of receptor for advanced glycation end-products (RAGE): a receptor involved in chronic inflammation.

    PubMed

    Syed, Aleem; Zhu, Qiaochu; Smith, Emily A

    2018-01-01

    Membrane diffusion is one of the key mechanisms in the cellular function of receptors. The signaling of receptors for advanced glycation end-products (RAGE) has been extensively studied in the context of several pathological conditions, however, very little is known about RAGE diffusion. To fill this gap, RAGE lateral diffusion is probed in native, cholesterol-depleted, and cytoskeleton-altered cellular conditions. In native GM07373 cellular conditions, RAGE has a 90% mobile fraction and an average diffusion coefficient of 0.3 μm 2 /s. When depolymerization of the actin cytoskeleton is inhibited with the small molecule jasplakinolide (Jsp), the RAGE mobile fraction and diffusion coefficient decrease by 22 and 37%, respectively. In contrast, depolymerizing the filamentous actin cytoskeleton using the small molecule cytochalasin D (CD) does not alter the RAGE diffusion properties. There is a 70 and 50% decrease in phosphorylation of extracellular signal-regulated kinase (p-ERK) when the actin cytoskeleton is disrupted by CD or Jsp, respectively, in RAGE-expressing GM07373 cells. Disrupting the actin cytoskeleton in GM07373 cells that do not express detectable amounts of RAGE results in no change in p-ERK. Cholesterol depletion results in no statistically significant change in the diffusion properties of RAGE or p-ERK. This work presents a strong link between the actin cytoskeleton and RAGE diffusion and downstream signaling, and serves to further our understanding of the factors influencing RAGE lateral diffusion.

  13. Ligand-directed tosyl chemistry for in situ native protein labeling and engineering in living systems: from basic properties to applications.

    PubMed

    Tsukiji, Shinya; Hamachi, Itaru

    2014-08-01

    The ability to introduce any chemical probe to any endogenous target protein in its native environment, that is in cells and in vivo, is anticipated to provide various new exciting tools for biological and biomedical research. Although still at the prototype stage, the ligand-directed tosyl (LDT) chemistry is a novel type of affinity labeling technique that we developed for such a dream. This chemistry allows for modifying native proteins by various chemical probes with high specificity in various biological settings ranging from in vitro (in test tubes) to in living cells and in vivo. Since the first report, the list of proteins that are successfully labeled by the LDT chemistry has been increasing. A growing number of studies have demonstrated its utility to create semisynthetic proteins directly in cellular contexts. The in situ generated semisynthetic proteins are applicable for various types of analysis and imaging of intracellular biological processes. In this review, we summarize the basic properties of the LDT chemistry and its applications toward in situ engineering and analysis of native proteins in living systems. Current limitations and future challenges of this area are also described. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. A Review of the Research Literature on the Influences of Culturally Based Education on the Academic Performance of Native American Students. Final Paper.

    ERIC Educational Resources Information Center

    Demmert, William G., Jr.; Towner, John C.

    There is a widespread, firm belief among Native American communities (American Indians, Alaska Natives, Native Hawaiians) and among professional Native educators that meaningful educational experiences require an appropriate language and cultural context. From their perspective, such context supports the traditions, knowledge, and language(s) of…

  15. Mathematics, thermodynamics, and modeling to address ten common misconceptions about protein structure, folding, and stability.

    PubMed

    Robic, Srebrenka

    2010-01-01

    To fully understand the roles proteins play in cellular processes, students need to grasp complex ideas about protein structure, folding, and stability. Our current understanding of these topics is based on mathematical models and experimental data. However, protein structure, folding, and stability are often introduced as descriptive, qualitative phenomena in undergraduate classes. In the process of learning about these topics, students often form incorrect ideas. For example, by learning about protein folding in the context of protein synthesis, students may come to an incorrect conclusion that once synthesized on the ribosome, a protein spends its entire cellular life time in its fully folded native confirmation. This is clearly not true; proteins are dynamic structures that undergo both local fluctuations and global unfolding events. To prevent and address such misconceptions, basic concepts of protein science can be introduced in the context of simple mathematical models and hands-on explorations of publicly available data sets. Ten common misconceptions about proteins are presented, along with suggestions for using equations, models, sequence, structure, and thermodynamic data to help students gain a deeper understanding of basic concepts relating to protein structure, folding, and stability.

  16. The emotional impact of being myself: Emotions and foreign-language processing.

    PubMed

    Ivaz, Lela; Costa, Albert; Duñabeitia, Jon Andoni

    2016-03-01

    Native languages are acquired in emotionally rich contexts, whereas foreign languages are typically acquired in emotionally neutral academic environments. As a consequence of this difference, it has been suggested that bilinguals' emotional reactivity in foreign-language contexts is reduced as compared with native language contexts. In the current study, we investigated whether this emotional distance associated with foreign languages could modulate automatic responses to self-related linguistic stimuli. Self-related stimuli enhance performance by boosting memory, speed, and accuracy as compared with stimuli unrelated to the self (the so-called self-bias effect). We explored whether this effect depends on the language context by comparing self-biases in a native and a foreign language. Two experiments were conducted with native Spanish speakers with a high level of English proficiency in which they were asked to complete a perceptual matching task during which they associated simple geometric shapes (circles, squares, and triangles) with the labels "you," "friend," and "other" either in their native or foreign language. Results showed a robust asymmetry in the self-bias in the native- and foreign-language contexts: A larger self-bias was found in the native than in the foreign language. An additional control experiment demonstrated that the same materials administered to a group of native English speakers yielded robust self-bias effects that were comparable in magnitude to the ones obtained with the Spanish speakers when tested in their native language (but not in their foreign language). We suggest that the emotional distance evoked by the foreign-language contexts caused these differential effects across language contexts. These results demonstrate that the foreign-language effects are pervasive enough to affect automatic stages of emotional processing. (c) 2016 APA, all rights reserved).

  17. Defining "Native Speaker" in Multilingual Settings: English as a Native Language in Asia

    ERIC Educational Resources Information Center

    Hansen Edwards, Jette G.

    2017-01-01

    The current study examines how and why speakers of English from multilingual contexts in Asia are identifying as native speakers of English. Eighteen participants from different contexts in Asia, including Singapore, Malaysia, India, Taiwan, and The Philippines, who self-identified as native speakers of English participated in hour-long interviews…

  18. Pharmacological profiling of the TRPV3 channel in recombinant and native assays.

    PubMed

    Grubisha, Olivera; Mogg, Adrian J; Sorge, Jessica L; Ball, Laura-Jayne; Sanger, Helen; Ruble, Cara L A; Folly, Elizabeth A; Ursu, Daniel; Broad, Lisa M

    2014-05-01

    Transient receptor potential vanilloid subtype 3 (TRPV3) is implicated in nociception and certain skin conditions. As such, it is an attractive target for pharmaceutical research. Understanding of endogenous TRPV3 function and pharmacology remains elusive as selective compounds and native preparations utilizing higher throughput methodologies are lacking. In this study, we developed medium-throughput recombinant and native cellular assays to assess the detailed pharmacological profile of human, rat and mouse TRPV3 channels. Medium-throughput cellular assays were developed using a Ca(2+) -sensitive dye and a fluorescent imaging plate reader. Human and rat TRPV3 pharmacology was examined in recombinant cell lines, while the mouse 308 keratinocyte cell line was used to assess endogenous TRPV3 activity. A recombinant rat TRPV3 cellular assay was successfully developed after solving a discrepancy in the published rat TRPV3 protein sequence. A medium-throughput, native, mouse TRPV3 keratinocyte assay was also developed and confirmed using genetic approaches. Whereas the recombinant human and rat TRPV3 assays exhibited similar agonist and antagonist profiles, the native mouse assay showed important differences, namely, TRPV3 activity was detected only in the presence of potentiator or during agonist synergy. Furthermore, the native assay was more sensitive to block by some antagonists. Our findings demonstrate similarities but also notable differences in TRPV3 pharmacology between recombinant and native systems. These findings offer insights into TRPV3 function and these assays should aid further research towards developing TRPV3 therapies. © 2013 The British Pharmacological Society.

  19. North America's Native Peoples: A Social Justice and Trauma Counseling Approach

    ERIC Educational Resources Information Center

    Turner, Sherri L.; Pope, Mark

    2009-01-01

    This article understands North America's indigenous peoples in the context of social justice. The authors discuss the role of legislation in shaping cultural contexts of indigenous people and influencing mental health issues in Native American communities. Trauma counseling with Native Americans is explored.

  20. Role of local sequence in the folding of cellular retinoic abinding protein I: structural propensities of reverse turns.

    PubMed

    Rotondi, Kenneth S; Gierasch, Lila M

    2003-07-08

    The experiments described here explore the role of local sequence in the folding of cellular retinoic acid binding protein I (CRABP I). This is a 136-residue, 10-stranded, antiparallel beta-barrel protein with seven beta-hairpins and is a member of the intracellular lipid binding protein (iLBP) family. The relative roles of local and global sequence information in governing the folding of this class of proteins are not well-understood. In question is whether the beta-turns are locally defined by short-range interactions within their sequences, and are thus able to play an active role in reducing the conformational space available to the folding chain, or whether the turns are passive, relying upon global forces to form. Short (six- and seven-residue) peptides corresponding to the seven CRABP I turns were analyzed by circular dichroism and NMR for their tendencies to take up the conformations they adopt in the context of the native protein. The results indicate that two of the peptides, encompassing turns III and IV in CRABP I, have a strong intrinsic bias to form native turns. Intriguingly, these turns are on linked hairpins in CRABP I and represent the best-conserved turns in the iLBP family. These results suggest that local sequence may play an important role in narrowing the conformational ensemble of CRABP I during folding.

  1. Word Stress and Pronunciation Teaching in English as a Lingua Franca Contexts

    ERIC Educational Resources Information Center

    Lewis, Christine; Deterding, David

    2018-01-01

    Traditionally, pronunciation was taught by reference to native-speaker models. However, as speakers around the world increasingly interact in English as a lingua franca (ELF) contexts, there is less focus on native-speaker targets, and there is wide acceptance that achieving intelligibility is crucial while mimicking native-speaker pronunciation…

  2. [Natural toxins in inter- and intraspecies interaction of human being (elements of ethnotoxinology)].

    PubMed

    Gelashvili, D B

    2002-01-01

    The author considers the application of natural toxins as arrow poison by Homo sapiens from ancient time till today for hunting and ethnic wars on the example of natives of Asia, Africa, South America and Oceania. Geographic isolation was important determining the spectrum of natural toxin sources and the methods of their application. Cellular and molecular mechanisms of arrow poisons effects are considered in biogeographical context: aconitin and strychnin in Asia, diamphotoxin in Africa, indole alcaloids of plants and steroid alcaloids of amphibian in Central and South America, palytoxin in Oceania islands. High efficiency and selective effect of natural toxins allow to use them as molecular markers in current studies of functional membrane architecture and cellular structures. Great differences in pace of civilization development leads to the co-existence at the beginning of the XXI century ethnic groups that use natural toxins as arrow poison and human beings that use the same toxins in fundamental and applied investigations within international scientific society.

  3. Ecophysiology of native and alien-invasive clams in an ocean warming context.

    PubMed

    Anacleto, Patrícia; Maulvault, Ana Luísa; Lopes, Vanessa M; Repolho, Tiago; Diniz, Mário; Nunes, Maria Leonor; Marques, António; Rosa, Rui

    2014-09-01

    Both climate change and biological invasions are among the most serious global environmental threats. Yet mechanisms underlying these eventual interactions remain unclear. The aim of this study was to undertake a comprehensive examination of the physiological and biochemical responses of native (Ruditapes decussatus) and alien-invasive (Ruditapes philippinarum) clams to environmental warming. We evaluated thermal tolerance limits (CTMax), routine metabolic rates (RMRs) and respective thermal sensitivity (Q10 values), critical oxygen partial pressure (Pcrit), heat shock response (HSP70/HSC70 levels), lipid peroxidation (MDA build-up) and antioxidant enzyme [glutathione-S-transferase (GST), catalase (CAT) and superoxide dismutase (SOD)] activities. Contrary to most studies that show that invasive species have a higher thermal tolerance than native congeners, here we revealed that the alien-invasive and native species had similar CTMax values. However, warming had a stronger effect on metabolism and oxidative status of the native R. decussatus, as indicated by the higher RMRs and HSP70/HSC70 and MDA levels, as well as GST, CAT and SOD activities. Moreover, we argue that the alien-invasive clams, instead of up-regulating energetically expensive cellular responses, have evolved a less demanding strategy to cope with short-term environmental (oxidative) stress-pervasive valve closure. Although efficient during stressful short-term periods to ensure isolation and guarantee longer survival, such adaptive behavioural strategy entails metabolic arrest (and the enhancement of anaerobic pathways), which to some extent will not be advantageous under the chronically warming conditions predicted in the future. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Through indigenous eyes: Native Americans and the HIV epidemic.

    PubMed

    Weaver, H N

    1999-02-01

    This article examines the phenomenon of HIV within the context of a Native American culture. Native Americans have some risk factors for HIV transmission that differ from those found in other populations. In addition, prevention and intervention activities with this population must consider cultural variables to maximize their effectiveness. Brief anecdotes are used to illustrate various concepts related to HIV and Native Americans and to include a human face along with facts and statistics. The author's unique perspective, coupled with a broad discussion of relevant issues enables non-Native American readers to understand better the phenomenon of HIV as it exists within a Native American context.

  5. The Emotional Impact of Being Myself: Emotions and Foreign-Language Processing

    ERIC Educational Resources Information Center

    Ivaz, Lela; Costa, Albert; Duñabeitia, Jon Andoni

    2016-01-01

    Native languages are acquired in emotionally rich contexts, whereas foreign languages are typically acquired in emotionally neutral academic environments. As a consequence of this difference, it has been suggested that bilinguals' emotional reactivity in foreign-language contexts is reduced as compared with native language contexts. In the current…

  6. Native and L2 Processing of Homonyms in Sentential Context

    ERIC Educational Resources Information Center

    Elston-Guttler, K.E.; Friederici, A.D.

    2005-01-01

    We compare native and non-native processing of homonyms in sentence context whose two most frequent meanings are nouns (e.g., sentence) or a noun and a verb (e.g., trip). With both participant groups, we conducted a combined reaction time (RT)/event-related brain potential (ERP) lexical decision experiment with two stimulus-onset asynchronies…

  7. A novel form of perceptual attunement: Context-dependent perception of a native contrast in 14-month-old infants.

    PubMed

    Fort, Mathilde; Brusini, Perrine; Carbajal, M Julia; Sun, Yue; Peperkamp, Sharon

    2017-08-01

    By the end of their first year of life, infants have become experts in discriminating the sounds of their native language, while they have lost the ability to discriminate non-native contrasts. This type of phonetic learning is referred to as perceptual attunement. In the present study, we investigated the emergence of a context-dependent form of perceptual attunement in infancy. Indeed, some native contrasts are not discriminated in certain phonological contexts by adults, due to the presence of a language-specific process that neutralizes the contrasts in those contexts. We used a mismatch design and recorded high-density Electroencephalography (EEG) in French-learning 14-month-olds. Our results show that similarly to French adults, infants fail to discriminate a native voicing contrast (e.g., [f] vs. [v]) when it occurs in a specific phonological context (e.g. [ofbe] vs. [ovbe], no mismatch response), while they successfully detected it in other phonological contexts (e.g., [ofne] vs. [ovne], mismatch response). The present results demonstrate for the first time that by the age of 14 months, infants' phonetic learning does not only rely on the processing of individual sounds, but also takes into account in a language-specific manner the phonological contexts in which these sounds occur. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Clonal analysis of lineage fate in native haematopoiesis.

    PubMed

    Rodriguez-Fraticelli, Alejo E; Wolock, Samuel L; Weinreb, Caleb S; Panero, Riccardo; Patel, Sachin H; Jankovic, Maja; Sun, Jianlong; Calogero, Raffaele A; Klein, Allon M; Camargo, Fernando D

    2018-01-11

    Haematopoiesis, the process of mature blood and immune cell production, is functionally organized as a hierarchy, with self-renewing haematopoietic stem cells and multipotent progenitor cells sitting at the very top. Multiple models have been proposed as to what the earliest lineage choices are in these primitive haematopoietic compartments, the cellular intermediates, and the resulting lineage trees that emerge from them. Given that the bulk of studies addressing lineage outcomes have been performed in the context of haematopoietic transplantation, current models of lineage branching are more likely to represent roadmaps of lineage potential than native fate. Here we use transposon tagging to clonally trace the fates of progenitors and stem cells in unperturbed haematopoiesis. Our results describe a distinct clonal roadmap in which the megakaryocyte lineage arises largely independently of other haematopoietic fates. Our data, combined with single-cell RNA sequencing, identify a functional hierarchy of unilineage- and oligolineage-producing clones within the multipotent progenitor population. Finally, our results demonstrate that traditionally defined long-term haematopoietic stem cells are a significant source of megakaryocyte-restricted progenitors, suggesting that the megakaryocyte lineage is the predominant native fate of long-term haematopoietic stem cells. Our study provides evidence for a substantially revised roadmap for unperturbed haematopoiesis, and highlights unique properties of multipotent progenitors and haematopoietic stem cells in situ.

  9. Perception of coarticulated tones by non-native listeners

    NASA Astrophysics Data System (ADS)

    Bent, Tessa

    2005-04-01

    Mandarin lexical tones vary in their acoustic realization depending on the surrounding context. Native listeners compensate for this tonal coarticulation when identifying tones in context. This study investigated how native English listeners handle tonal coarticulation by testing native English and Mandarin listeners discrimination of the four Mandarin lexical tones in tri-syllabic sequences in which the middle tone varied while the first and last tones were held constant. Three different such frames were tested. As expected, Mandarin listeners discriminated all pairs in all contexts with a high degree of accuracy. English listeners exhibited poorer discrimination than Mandarin listeners and their discrimination accuracy showed a high degree of context dependency. In addition to assessing accuracy, reactions times to correctly discriminated different trials were entered into a multidimensional scaling analysis. For both listener groups, the arrangement of tones in perceptual space varied depending on the surrounding context suggesting that listeners attend to different acoustic attributes of the target tone depending on the surrounding tones. These results demonstrate the importance for models of cross-language speech perception of including contextual variation when characterizing the perception of non-native prosodic categories. [Work supported by NIH/NIDCD

  10. Pharmacological profiling of the TRPV3 channel in recombinant and native assays

    PubMed Central

    Grubisha, Olivera; Mogg, Adrian J; Sorge, Jessica L; Ball, Laura-Jayne; Sanger, Helen; Ruble, Cara L A; Folly, Elizabeth A; Ursu, Daniel; Broad, Lisa M

    2014-01-01

    Background and Purpose Transient receptor potential vanilloid subtype 3 (TRPV3) is implicated in nociception and certain skin conditions. As such, it is an attractive target for pharmaceutical research. Understanding of endogenous TRPV3 function and pharmacology remains elusive as selective compounds and native preparations utilizing higher throughput methodologies are lacking. In this study, we developed medium-throughput recombinant and native cellular assays to assess the detailed pharmacological profile of human, rat and mouse TRPV3 channels. Experimental Approach Medium-throughput cellular assays were developed using a Ca2+-sensitive dye and a fluorescent imaging plate reader. Human and rat TRPV3 pharmacology was examined in recombinant cell lines, while the mouse 308 keratinocyte cell line was used to assess endogenous TRPV3 activity. Key Results A recombinant rat TRPV3 cellular assay was successfully developed after solving a discrepancy in the published rat TRPV3 protein sequence. A medium-throughput, native, mouse TRPV3 keratinocyte assay was also developed and confirmed using genetic approaches. Whereas the recombinant human and rat TRPV3 assays exhibited similar agonist and antagonist profiles, the native mouse assay showed important differences, namely, TRPV3 activity was detected only in the presence of potentiator or during agonist synergy. Furthermore, the native assay was more sensitive to block by some antagonists. Conclusions and Implications Our findings demonstrate similarities but also notable differences in TRPV3 pharmacology between recombinant and native systems. These findings offer insights into TRPV3 function and these assays should aid further research towards developing TRPV3 therapies. Linked Articles This article is part of a themed section on the pharmacology of TRP channels. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-10 PMID:23848361

  11. Effects of Language Context on Ratings of Shy and Unsociable Behaviors in English Language Learning Children

    PubMed Central

    Ash, Andrea C.; Rice, Mabel L.; Redmond, Sean M.

    2014-01-01

    Purpose The primary goal of this study was to explore the effect of the language context on the socially withdrawn behaviors of school aged-children who are English Language Learners (ELLs) from middle to high SES backgrounds. This is one of the first studies to address the frequently confused concepts of shyness and unsociability as independent constructs within the ELL population. This study also investigated the feasibility of an experimental parent and child questionnaire that examines shyness and unsociability across native and English speaking contexts. Method Children and parents (34 ELL and 37 native English speaking) were administered an experimental questionnaire examining shy and unsociable behavior in native language and English-speaking contexts. Results Parents and children from the ELL group reported significantly higher ratings of shy behavior in English versus native language contexts, whereas unsociable ratings did not differ across language contexts. Conclusions Shyness and unsociability are distinguishable behaviors in ELL children and these constructs should be considered when examining withdrawal. Additionally, examining ELL children’s behavior across language contexts provides a valuable method for investigating language influenced behavioral problems. This study demonstrates the need for service providers to evaluate behavior across subtype and language context before pathologizing withdrawal in ELL children. PMID:24687767

  12. Blood Politics, Ethnic Identity, and Racial Misclassification among American Indians and Alaska Natives

    PubMed Central

    Haozous, Emily A.; Strickland, Carolyn J.; Palacios, Janelle F.; Solomon, Teshia G. Arambula

    2014-01-01

    Misclassification of race in medical and mortality records has long been documented as an issue in American Indian/Alaska Native data. Yet, little has been shared in a cohesive narrative which outlines why misclassification of American Indian/Alaska Native identity occurs. The purpose of this paper is to provide a summary of the current state of the science in racial misclassification among American Indians and Alaska Natives. We also provide a historical context on the importance of this problem and describe the ongoing political processes that both affect racial misclassification and contribute to the context of American Indian and Alaska Native identity. PMID:24669226

  13. Blood politics, ethnic identity, and racial misclassification among American Indians and Alaska Natives.

    PubMed

    Haozous, Emily A; Strickland, Carolyn J; Palacios, Janelle F; Solomon, Teshia G Arambula

    2014-01-01

    Misclassification of race in medical and mortality records has long been documented as an issue in American Indian/Alaska Native data. Yet, little has been shared in a cohesive narrative which outlines why misclassification of American Indian/Alaska Native identity occurs. The purpose of this paper is to provide a summary of the current state of the science in racial misclassification among American Indians and Alaska Natives. We also provide a historical context on the importance of this problem and describe the ongoing political processes that both affect racial misclassification and contribute to the context of American Indian and Alaska Native identity.

  14. In silico design of context-responsive mammalian promoters with user-defined functionality

    PubMed Central

    Gibson, Suzanne J.; Hatton, Diane

    2017-01-01

    Abstract Comprehensive de novo-design of complex mammalian promoters is restricted by unpredictable combinatorial interactions between constituent transcription factor regulatory elements (TFREs). In this study, we show that modular binding sites that do not function cooperatively can be identified by analyzing host cell transcription factor expression profiles, and subsequently testing cognate TFRE activities in varying homotypic and heterotypic promoter architectures. TFREs that displayed position-insensitive, additive function within a specific expression context could be rationally combined together in silico to create promoters with highly predictable activities. As TFRE order and spacing did not affect the performance of these TFRE-combinations, compositions could be specifically arranged to preclude the formation of undesirable sequence features. This facilitated simple in silico-design of promoters with context-required, user-defined functionalities. To demonstrate this, we de novo-created promoters for biopharmaceutical production in CHO cells that exhibited precisely designed activity dynamics and long-term expression-stability, without causing observable retroactive effects on cellular performance. The design process described can be utilized for applications requiring context-responsive, customizable promoter function, particularly where co-expression of synthetic TFs is not suitable. Although the synthetic promoter structure utilized does not closely resemble native mammalian architectures, our findings also provide additional support for a flexible billboard model of promoter regulation. PMID:28977454

  15. Writing on the walls: Geological context and early American spiritual beliefs

    USGS Publications Warehouse

    Hough, S.E.; ,

    2007-01-01

    Native American culture in many parts of California is preserved in fragmentary oral and conventional written histories, but also in sometimes dramatic petroglyphs and pictographs throughout the state. The symbolism of these images has been interpreted to reflect the natural environment, in particular issues related to rain. Although there is little doubt that rain was of paramount concern to native tribes, I suggest that geological context also played an important role in shaping early spiritual beliefs in general, and petroglyph sites in particular. From the standpoint of Native American philosophies and spiritual beliefs, geological unrest is not merely a reflection but in some cases an actual embodiment of the spiritual world. To understand the significance of petroglyph sites, they must be considered in the context of overall Native American beliefs. In this context, sites of repeated geological unrest would invariably have evolved great spiritual significance. Petroglyph locations and ages may thus provide independent age controls on 'prehistoric' earthquakes in California. ?? The Geological Society of London 2007.

  16. Correlative Microscopy of Vitreous Sections Provides Insights into BAR-Domain Organization In Situ.

    PubMed

    Bharat, Tanmay A M; Hoffmann, Patrick C; Kukulski, Wanda

    2018-04-10

    Electron microscopy imaging of macromolecular complexes in their native cellular context is limited by the inherent difficulty to acquire high-resolution tomographic data from thick cells and to specifically identify elusive structures within crowded cellular environments. Here, we combined cryo-fluorescence microscopy with electron cryo-tomography of vitreous sections into a coherent correlative microscopy workflow, ideal for detection and structural analysis of elusive protein assemblies in situ. We used this workflow to address an open question on BAR-domain coating of yeast plasma membrane compartments known as eisosomes. BAR domains can sense or induce membrane curvature, and form scaffold-like membrane coats in vitro. Our results demonstrate that in cells, the BAR protein Pil1 localizes to eisosomes of varying membrane curvature. Sub-tomogram analysis revealed a dense protein coat on curved eisosomes, which was not present on shallow eisosomes, indicating that while BAR domains can assemble at shallow membranes in vivo, scaffold formation is tightly coupled to curvature generation. Copyright © 2018 MRC Laboratory of Molecular Biology. Published by Elsevier Ltd.. All rights reserved.

  17. Sequence context and crosslinking mechanism affect the efficiency of in vivo capture of a protein-protein interaction

    PubMed Central

    Lancia, Jody K.; Nwokoye, Adaora; Dugan, Amanda; Joiner, Cassandra; Pricer, Rachel; Mapp, Anna K.

    2014-01-01

    Protein-protein interactions (PPIs) are essential for implementing cellular processes and thus methods for the discovery and study of PPIs are highly desirable. An emerging method for capturing PPIs in their native cellular environment is in vivo covalent chemical capture, a method that uses nonsense suppression to site specifically incorporate photoactivable unnatural amino acids in living cells. However, in one study we found that this method did not capture a PPI for which there was abundant functional evidence, a complex formed between the transcriptional activator Gal4 and its repressor protein Gal80. Here we describe the factors that influence the success of covalent chemical capture and show that the innate reactivity of the two unnatural amino acids utilized, (p-benzoylphenylalanine (pBpa) and p-azidophenylalanine (pAzpa)), plays a profound role in the capture of Gal80 by Gal4. Based upon these data, guidelines are outlined for the successful use of in vivo photo-crosslinking to capture novel PPIs and to characterize the interfaces. PMID:24037947

  18. Reduced native state stability in crowded cellular environment due to protein-protein interactions.

    PubMed

    Harada, Ryuhei; Tochio, Naoya; Kigawa, Takanori; Sugita, Yuji; Feig, Michael

    2013-03-06

    The effect of cellular crowding environments on protein structure and stability is a key issue in molecular and cellular biology. The classical view of crowding emphasizes the volume exclusion effect that generally favors compact, native states. Here, results from molecular dynamics simulations and NMR experiments show that protein crowders may destabilize native states via protein-protein interactions. In the model system considered here, mixtures of villin head piece and protein G at high concentrations, villin structures become increasingly destabilized upon increasing crowder concentrations. The denatured states observed in the simulation involve partial unfolding as well as more subtle conformational shifts. The unfolded states remain overall compact and only partially overlap with unfolded ensembles at high temperature and in the presence of urea. NMR measurements on the same systems confirm structural changes upon crowding based on changes of chemical shifts relative to dilute conditions. An analysis of protein-protein interactions and energetic aspects suggests the importance of enthalpic and solvation contributions to the crowding free energies that challenge an entropic-centered view of crowding effects.

  19. Electron cryo-tomography captures macromolecular complexes in native environments.

    PubMed

    Baker, Lindsay A; Grange, Michael; Grünewald, Kay

    2017-10-01

    Transmission electron microscopy has a long history in cellular biology. Fixed and stained samples have been used for cellular imaging for over 50 years, but suffer from sample preparation induced artifacts. Electron cryo-tomography (cryoET) instead uses frozen-hydrated samples, without chemical modification, to determine the structure of macromolecular complexes in their native environment. Recent developments in electron microscopes and associated technologies have greatly expanded our ability to visualize cellular features and determine the structures of macromolecular complexes in situ. This review highlights the technological improvements and the new areas of biology these advances have made accessible. We discuss the potential of cryoET to reveal novel and significant biological information on the nanometer or subnanometer scale, and directions for further work. Copyright © 2017. Published by Elsevier Ltd.

  20. Native American Children in Michigan. [Executive Summary

    ERIC Educational Resources Information Center

    W. K. Kellogg Foundation, 2012

    2012-01-01

    "Native American Children in Michigan," provides a historical context for the tenuous relationship between Michigan's 12 federally recognized tribes and the state government, paying particular attention to the erosion of Native American education programs and the disproportionate number of Native children who find themselves in both the…

  1. A new perspective on trait differences between native and invasive exotic plants.

    PubMed

    Leffler, A Joshua; James, Jeremy J; Monaco, Thomas A; Sheley, Roger L

    2014-02-01

    Functional differences between native and exotic species potentially constitute one factor responsible for plant invasion. Differences in trait values between native and exotic invasive species, however, should not be considered fixed and may depend on the context of the comparison. Furthermore, the magnitude of difference between native and exotic species necessary to trigger invasion is unknown. We propose a criterion that differences in trait values between a native and exotic invasive species must be greater than differences between co-occurring natives for this difference to be ecologically meaningful and a contributing factor to plant invasion. We used a meta-analysis to quantify the difference between native and exotic invasive species for various traits examined in previous studies and compared this value to differences among native species reported in the same studies. The effect size between native and exotic invasive species was similar to the effect size between co-occurring natives except for studies conducted in the field; in most instances, our criterion was not met although overall differences between native and exotic invasive species were slightly larger than differences between natives. Consequently, trait differences may be important in certain contexts, but other mechanisms of invasion are likely more important in most cases. We suggest that using trait values as predictors of invasion will be challenging.

  2. Syntactic Constraints and Individual Differences in Native and Non-Native Processing of Wh-Movement

    PubMed Central

    Johnson, Adrienne; Fiorentino, Robert; Gabriele, Alison

    2016-01-01

    There is a debate as to whether second language (L2) learners show qualitatively similar processing profiles as native speakers or whether L2 learners are restricted in their ability to use syntactic information during online processing. In the realm of wh-dependency resolution, research has examined whether learners, similar to native speakers, attempt to resolve wh-dependencies in grammatically licensed contexts but avoid positing gaps in illicit contexts such as islands. Also at issue is whether the avoidance of gap filling in islands is due to adherence to syntactic constraints or whether islands simply present processing bottlenecks. One approach has been to examine the relationship between processing abilities and the establishment of wh-dependencies in islands. Grammatical accounts of islands do not predict such a relationship as the parser should simply not predict gaps in illicit contexts. In contrast, a pattern of results showing that individuals with more processing resources are better able to establish wh-dependencies in islands could conceivably be compatible with certain processing accounts. In a self-paced reading experiment which examines the processing of wh-dependencies, we address both questions, examining whether native English speakers and Korean learners of English show qualitatively similar patterns and whether there is a relationship between working memory, as measured by counting span and reading span, and processing in both island and non-island contexts. The results of the self-paced reading experiment suggest that learners can use syntactic information on the same timecourse as native speakers, showing qualitative similarity between the two groups. Results of regression analyses did not reveal a significant relationship between working memory and the establishment of wh-dependencies in islands but we did observe significant relationships between working memory and the processing of licit wh-dependencies. As the contexts in which these relationships emerged differed for learners and native speakers, our results call for further research examining individual differences in dependency resolution in both populations. PMID:27148152

  3. Syntactic Constraints and Individual Differences in Native and Non-Native Processing of Wh-Movement.

    PubMed

    Johnson, Adrienne; Fiorentino, Robert; Gabriele, Alison

    2016-01-01

    There is a debate as to whether second language (L2) learners show qualitatively similar processing profiles as native speakers or whether L2 learners are restricted in their ability to use syntactic information during online processing. In the realm of wh-dependency resolution, research has examined whether learners, similar to native speakers, attempt to resolve wh-dependencies in grammatically licensed contexts but avoid positing gaps in illicit contexts such as islands. Also at issue is whether the avoidance of gap filling in islands is due to adherence to syntactic constraints or whether islands simply present processing bottlenecks. One approach has been to examine the relationship between processing abilities and the establishment of wh-dependencies in islands. Grammatical accounts of islands do not predict such a relationship as the parser should simply not predict gaps in illicit contexts. In contrast, a pattern of results showing that individuals with more processing resources are better able to establish wh-dependencies in islands could conceivably be compatible with certain processing accounts. In a self-paced reading experiment which examines the processing of wh-dependencies, we address both questions, examining whether native English speakers and Korean learners of English show qualitatively similar patterns and whether there is a relationship between working memory, as measured by counting span and reading span, and processing in both island and non-island contexts. The results of the self-paced reading experiment suggest that learners can use syntactic information on the same timecourse as native speakers, showing qualitative similarity between the two groups. Results of regression analyses did not reveal a significant relationship between working memory and the establishment of wh-dependencies in islands but we did observe significant relationships between working memory and the processing of licit wh-dependencies. As the contexts in which these relationships emerged differed for learners and native speakers, our results call for further research examining individual differences in dependency resolution in both populations.

  4. Hotspot Mutations in KIT Receptor Differentially Modulate Its Allosterically Coupled Conformational Dynamics: Impact on Activation and Drug Sensitivity

    PubMed Central

    Chauvot de Beauchêne, Isaure; Allain, Ariane; Panel, Nicolas; Laine, Elodie; Trouvé, Alain; Dubreuil, Patrice; Tchertanov, Luba

    2014-01-01

    Receptor tyrosine kinase KIT controls many signal transduction pathways and represents a typical allosterically regulated protein. The mutation-induced deregulation of KIT activity impairs cellular physiological functions and causes serious human diseases. The impact of hotspots mutations (D816H/Y/N/V and V560G/D) localized in crucial regulatory segments, the juxtamembrane region (JMR) and the activation (A-) loop, on KIT internal dynamics was systematically studied by molecular dynamics simulations. The mutational outcomes predicted in silico were correlated with in vitro and in vivo activation rates and drug sensitivities of KIT mutants. The allosteric regulation of KIT in the native and mutated forms is described in terms of communication between the two remote segments, JMR and A-loop. A strong correlation between the communication profile and the structural and dynamical features of KIT in the native and mutated forms was established. Our results provide new insight on the determinants of receptor KIT constitutive activation by mutations and resistance of KIT mutants to inhibitors. Depiction of an intra-molecular component of the communication network constitutes a first step towards an integrated description of vast communication pathways established by KIT in physiopathological contexts. PMID:25079768

  5. Prospect of Electronic Media as Curriculum in Non-Native Contexts

    ERIC Educational Resources Information Center

    Dutta, Juri; Parhi, Asima Ranjan

    2014-01-01

    In the context of India in general, and places where English language functions as a second language in particular, the prevalent idea that our students have to support their language learning capability through the native accent (pronunciation) structures is a myth. The paper takes up the following hypotheses: 1. Listening to BBC English or…

  6. Modular extracellular sensor architecture for engineering mammalian cell-based devices.

    PubMed

    Daringer, Nichole M; Dudek, Rachel M; Schwarz, Kelly A; Leonard, Joshua N

    2014-12-19

    Engineering mammalian cell-based devices that monitor and therapeutically modulate human physiology is a promising and emerging frontier in clinical synthetic biology. However, realizing this vision will require new technologies enabling engineered circuitry to sense and respond to physiologically relevant cues. No existing technology enables an engineered cell to sense exclusively extracellular ligands, including proteins and pathogens, without relying upon native cellular receptors or signal transduction pathways that may be subject to crosstalk with native cellular components. To address this need, we here report a technology we term a Modular Extracellular Sensor Architecture (MESA). This self-contained receptor and signal transduction platform is maximally orthogonal to native cellular processes and comprises independent, tunable protein modules that enable performance optimization and straightforward engineering of novel MESA that recognize novel ligands. We demonstrate ligand-inducible activation of MESA signaling, optimization of receptor performance using design-based approaches, and generation of MESA biosensors that produce outputs in the form of either transcriptional regulation or transcription-independent reconstitution of enzymatic activity. This systematic, quantitative platform characterization provides a framework for engineering MESA to recognize novel ligands and for integrating these sensors into diverse mammalian synthetic biology applications.

  7. Correlation of cellular factors and differential scrapie prion permissiveness in ovine microglia

    USDA-ARS?s Scientific Manuscript database

    Prion diseases are fatal neurodegenerative disorders by which the native cellular prion protein (PrP-C) is misfolded into an accumulating, disease-associated isoform (PrP-D). To improve the understanding of prion pathogenesis and develop effective treatments, it is essential to elucidate factors con...

  8. Kinase Substrate Sensor (KISS), a Mammalian In Situ Protein Interaction Sensor*

    PubMed Central

    Lievens, Sam; Gerlo, Sarah; Lemmens, Irma; De Clercq, Dries J. H.; Risseeuw, Martijn D. P.; Vanderroost, Nele; De Smet, Anne-Sophie; Ruyssinck, Elien; Chevet, Eric; Van Calenbergh, Serge; Tavernier, Jan

    2014-01-01

    Probably every cellular process is governed by protein-protein interaction (PPIs), which are often highly dynamic in nature being modulated by in- or external stimuli. Here we present KISS, for KInase Substrate Sensor, a mammalian two-hybrid approach designed to map intracellular PPIs and some of the dynamic features they exhibit. Benchmarking experiments indicate that in terms of sensitivity and specificity KISS is on par with other binary protein interaction technologies while being complementary with regard to the subset of PPIs it is able to detect. We used KISS to evaluate interactions between different types of proteins, including transmembrane proteins, expressed at their native subcellular location. In situ analysis of endoplasmic reticulum stress-induced clustering of the endoplasmic reticulum stress sensor ERN1 and ligand-dependent β-arrestin recruitment to GPCRs illustrated the method's potential to study functional PPI modulation in complex cellular processes. Exploring its use as a tool for in cell evaluation of pharmacological interference with PPIs, we showed that reported effects of known GPCR antagonists and PPI inhibitors are properly recapitulated. In a three-hybrid setup, KISS was able to map interactions between small molecules and proteins. Taken together, we established KISS as a sensitive approach for in situ analysis of protein interactions and their modulation in a changing cellular context or in response to pharmacological challenges. PMID:25154561

  9. The People: Reflections of Native Peoples on the Catholic Experience in North America.

    ERIC Educational Resources Information Center

    Hall, Suzanne, Ed.

    Four Native American Catholic priests and nuns reflect on the 500-year history of Roman Catholic evangelization among Native Americans and call for a reconciliation of all the peoples of the Americas. P. Michael Galvan outlines the historical context of Native-Church relations since 1492, notes the negative and positive outcomes of the collision…

  10. Risk and Protective Factors for HIV/AIDS in Native Americans: Implications for Preventive Intervention

    ERIC Educational Resources Information Center

    Dennis, Mary Kate

    2009-01-01

    HIV/AIDS has steadily increased in Native American and Alaska Native populations, and despite efforts at control many challenges remain. This article examines historical, biological, social, and behavioral cofactors related to the spread of HIV/AIDS within the context of Native American culture. Special attention is given to vulnerable subgroups…

  11. Adding More Fuel to the Fire: An Eye-Tracking Study of Idiom Processing by Native and Non-Native Speakers

    ERIC Educational Resources Information Center

    Siyanova-Chanturia, Anna; Conklin, Kathy; Schmitt, Norbert

    2011-01-01

    Using eye-tracking, we investigate on-line processing of idioms in a biasing story context by native and non-native speakers of English. The stimuli are idioms used figuratively ("at the end of the day"--"eventually"), literally ("at the end of the day"--"in the evening"), and novel phrases ("at the end of the war"). Native speaker results…

  12. Forming Physical Education Teachers' Pedagogical Mastery in the Context of Native and Foreign Scholars' Views

    ERIC Educational Resources Information Center

    Maksymchuk, Iryna

    2016-01-01

    The article deals with studying the process of forming physical education teachers' pedagogical mastery in the context of native and foreign scholars' views. It has been indicated that the problem of pedagogical activity and pedagogical mastery efficiency has been raised in the works of a number of scholars who developed the principles and…

  13. The Interpretation of "in Context" Verbal Probability Expressions Used in International Accounting Standards: A Comparison of English and Chinese Students Studying at English Speaking Universities

    ERIC Educational Resources Information Center

    Salleh, Safrul Izani Mohd; Gardner, John C.; Sulong, Zunaidah; McGowan, Carl B., Jr.

    2011-01-01

    This study examines the differences in the interpretation of ten "in context" verbal probability expressions used in accounting standards between native Chinese speaking and native English speaking accounting students in United Kingdom universities. The study assesses the degree of grouping factors consensus on the numerical…

  14. A COTS-Based Replacement Strategy for Aging Avionics Computers

    DTIC Science & Technology

    2001-12-01

    Communication Control Unit. A COTS-Based Replacement Strategy for Aging Avionics Computers COTS Microprocessor Real Time Operating System New Native Code...Native Code Objec ts Native Code Thread Real - Time Operating System Legacy Function x Virtual Component Environment Context Switch Thunk Add-in Replace

  15. Revisiting the role of language in spatial cognition: Categorical perception of spatial relations in English and Korean speakers.

    PubMed

    Holmes, Kevin J; Moty, Kelsey; Regier, Terry

    2017-12-01

    The spatial relation of support has been regarded as universally privileged in nonlinguistic cognition and immune to the influence of language. English, but not Korean, obligatorily distinguishes support from nonsupport via basic spatial terms. Despite this linguistic difference, previous research suggests that English and Korean speakers show comparable nonlinguistic sensitivity to the support/nonsupport distinction. Here, using a paradigm previously found to elicit cross-language differences in color discrimination, we provide evidence for a difference in sensitivity to support/nonsupport between native English speakers and native Korean speakers who were late English learners and tested in a context that privileged Korean. Whereas the former group showed categorical perception (CP) when discriminating spatial scenes capturing the support/nonsupport distinction, the latter did not. An additional group of native Korean speakers-relatively early English learners tested in an English-salient context-patterned with the native English speakers in showing CP for support/nonsupport. These findings suggest that obligatory marking of support/nonsupport in one's native language can affect nonlinguistic sensitivity to this distinction, contra earlier findings, but that such sensitivity may also depend on aspects of language background and the immediate linguistic context.

  16. Photoactivatable protein labeling by singlet oxygen mediated reactions.

    PubMed

    To, Tsz-Leung; Medzihradszky, Katalin F; Burlingame, Alma L; DeGrado, William F; Jo, Hyunil; Shu, Xiaokun

    2016-07-15

    Protein-protein interactions regulate many biological processes. Identification of interacting proteins is thus an important step toward molecular understanding of cell signaling. The aim of this study was to investigate the use of photo-generated singlet oxygen and a small molecule for proximity labeling of interacting proteins in cellular environment. The protein of interest (POI) was fused with a small singlet oxygen photosensitizer (miniSOG), which generates singlet oxygen ((1)O2) upon irradiation. The locally generated singlet oxygen then activated a biotin-conjugated thiol molecule to form a covalent bond with the proteins nearby. The labeled proteins can then be separated and subsequently identified by mass spectrometry. To demonstrate the applicability of this labeling technology, we fused the miniSOG to Skp2, an F-box protein of the SCF ubiquitin ligase, and expressed the fusion protein in mammalian cells and identified that the surface cysteine of its interacting partner Skp1 was labeled by the biotin-thiol molecule. This photoactivatable protein labeling method may find important applications including identification of weak and transient protein-protein interactions in the native cellular context, as well as spatial and temporal control of protein labeling. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. When the Native Is Also a Non-Native: "Retrodicting" the Complexity of Language Teacher Cognition

    ERIC Educational Resources Information Center

    Aslan, Erhan

    2015-01-01

    The impact of native (NS) and non-native speaker (NNS) identities on second or foreign language teachers' cognition and practices in the classroom has mainly been investigated in ESL/EFL contexts. Using complexity theory as a framework, this case study attempts to fill the gap in the literature by presenting a foreign language teacher in the…

  18. Can We Teach Digital Natives Digital Literacy?

    ERIC Educational Resources Information Center

    Ng, Wan

    2012-01-01

    In recent years, there has been much debate about the concept of digital natives, in particular the differences between the digital natives' knowledge and adoption of digital technologies in informal versus formal educational contexts. This paper investigates the knowledge about educational technologies of a group of undergraduate students…

  19. Use of Referential Discourse Contexts in L2 Offline and Online Sentence Processing.

    PubMed

    Yang, Pi-Lan

    2016-10-01

    The present study aimed to investigate (a) the extent to which Chinese-speaking learners of English in Taiwan use referential noun phrase (NP) information contained in discourse contexts to complete ambiguous noun/verb fragments in a sentence completion task, and (b) whether and when they use the contexts to disambiguate main verb versus reduced relative clause (MV/RRC) ambiguities in real time. Results showed that unlike native English speakers, English learners did not create a marked increase in RRC completions in biasing two-NP-referent discourse contexts except for advanced learners. Nevertheless, like native speakers, the learners at elementary, intermediate, and advanced English proficiency levels all used the information in a later stage of resolving the MV/RRC ambiguities in real time. The delayed effect of referential context information observed suggests that L2 learners, like native speakers, are able to construct syntax-to-discourse mappings in real time. It also suggests that processing of syntactic information takes precedence over integration of syntactic information with discourse information during L1 and L2 online sentence processing.

  20. Integrative Approaches of Native and Foreign Scholars to Pedology in the Context of Views of the Third Millennium

    ERIC Educational Resources Information Center

    Kuzminsky, Anatoliy

    2016-01-01

    Problems of appearing and functioning of human study science, i.e. pedology, have been studied in the paper. Theoretical analysis of integrative approaches of native and foreign scholars to pedology in the context of views of the third millennium has been performed. Useful and positive achievements of this science as well as wrong ones determined…

  1. NESTs, Necessary or Not? Examining the Impact of Native English Speaker Instruction in South Korea

    ERIC Educational Resources Information Center

    Schenck, Andrew

    2018-01-01

    Although Native English-Speaking Teachers (NESTs) are extensively utilized, very little is known about the impact of these teachers on speaking or writing in Asian contexts like South Korea. The purpose of this study was to examine the impact of NEST instruction on EFL learners' speech in a South Korean context. First, proficiency level of 100…

  2. High-Fidelity Tissue Engineering of Patient-Specific Auricles for Reconstruction of Pediatric Microtia and Other Auricular Deformities

    PubMed Central

    Reiffel, Alyssa J.; Kafka, Concepcion; Hernandez, Karina A.; Popa, Samantha; Perez, Justin L.; Zhou, Sherry; Pramanik, Satadru; Brown, Bryan N.; Ryu, Won Seuk; Bonassar, Lawrence J.; Spector, Jason A.

    2013-01-01

    Introduction Autologous techniques for the reconstruction of pediatric microtia often result in suboptimal aesthetic outcomes and morbidity at the costal cartilage donor site. We therefore sought to combine digital photogrammetry with CAD/CAM techniques to develop collagen type I hydrogel scaffolds and their respective molds that would precisely mimic the normal anatomy of the patient-specific external ear as well as recapitulate the complex biomechanical properties of native auricular elastic cartilage while avoiding the morbidity of traditional autologous reconstructions. Methods Three-dimensional structures of normal pediatric ears were digitized and converted to virtual solids for mold design. Image-based synthetic reconstructions of these ears were fabricated from collagen type I hydrogels. Half were seeded with bovine auricular chondrocytes. Cellular and acellular constructs were implanted subcutaneously in the dorsa of nude rats and harvested after 1 and 3 months. Results Gross inspection revealed that acellular implants had significantly decreased in size by 1 month. Cellular constructs retained their contour/projection from the animals' dorsa, even after 3 months. Post-harvest weight of cellular constructs was significantly greater than that of acellular constructs after 1 and 3 months. Safranin O-staining revealed that cellular constructs demonstrated evidence of a self-assembled perichondrial layer and copious neocartilage deposition. Verhoeff staining of 1 month cellular constructs revealed de novo elastic cartilage deposition, which was even more extensive and robust after 3 months. The equilibrium modulus and hydraulic permeability of cellular constructs were not significantly different from native bovine auricular cartilage after 3 months. Conclusions We have developed high-fidelity, biocompatible, patient-specific tissue-engineered constructs for auricular reconstruction which largely mimic the native auricle both biomechanically and histologically, even after an extended period of implantation. This strategy holds immense potential for durable patient-specific tissue-engineered anatomically proper auricular reconstructions in the future. PMID:23437148

  3. Culturally Responsive Mathematics and Science Education for Native Students.

    ERIC Educational Resources Information Center

    Nelson-Barber, Sharon; Estrin, Elise Trumbull

    This monograph addresses concerns about mathematics and science instruction and educational outcomes for Native students. The sociocultural contexts of schooling and community come together in particular ways to influence how Native children learn and, consequently, their life outcomes. It is important to look beyond the performance of individual…

  4. Native Reactions to Non-Native Speech: A Review of Empirical Research.

    ERIC Educational Resources Information Center

    Eisenstein, Miriam

    1983-01-01

    Recent research on native speakers' reactions to nonnative speech that views listeners, speakers, and language from a variety of perspectives using both objective and subjective research paradigms is reviewed. Studies of error gravity, relative intelligibility of language samples, the role of accent, speakers' characteristics, and context in which…

  5. Proteomic differences between native and tissue-engineered tendon and ligament.

    PubMed

    Kharaz, Yalda A; Tew, Simon R; Peffers, Mandy; Canty-Laird, Elizabeth G; Comerford, Eithne

    2016-05-01

    Tendons and ligaments (T/Ls) play key roles in the musculoskeletal system, but they are susceptible to traumatic or age-related rupture, leading to severe morbidity as well as increased susceptibility to degenerative joint diseases such as osteoarthritis. Tissue engineering represents an attractive therapeutic approach to treating T/L injury but it is hampered by our poor understanding of the defining characteristics of the two tissues. The present study aimed to determine differences in the proteomic profile between native T/Ls and tissue engineered (TE) T/L constructs. The canine long digital extensor tendon and anterior cruciate ligament were analyzed along with 3D TE fibrin-based constructs created from their cells. Native tendon and ligament differed in their content of key structural proteins, with the ligament being more abundant in fibrocartilaginous proteins. 3D T/L TE constructs contained less extracellular matrix (ECM) proteins and had a greater proportion of cellular-associated proteins than native tissue, corresponding to their low collagen and high DNA content. Constructs were able to recapitulate native T/L tissue characteristics particularly with regard to ECM proteins. However, 3D T/L TE constructs had similar ECM and cellular protein compositions indicating that cell source may not be an important factor for T/L tissue engineering. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Native aggregation as a cause of origin of temporary cellular structures needed for all forms of cellular activity, signaling and transformations.

    PubMed

    Matveev, Vladimir V

    2010-06-09

    According to the hypothesis explored in this paper, native aggregation is genetically controlled (programmed) reversible aggregation that occurs when interacting proteins form new temporary structures through highly specific interactions. It is assumed that Anfinsen's dogma may be extended to protein aggregation: composition and amino acid sequence determine not only the secondary and tertiary structure of single protein, but also the structure of protein aggregates (associates). Cell function is considered as a transition between two states (two states model), the resting state and state of activity (this applies to the cell as a whole and to its individual structures). In the resting state, the key proteins are found in the following inactive forms: natively unfolded and globular. When the cell is activated, secondary structures appear in natively unfolded proteins (including unfolded regions in other proteins), and globular proteins begin to melt and their secondary structures become available for interaction with the secondary structures of other proteins. These temporary secondary structures provide a means for highly specific interactions between proteins. As a result, native aggregation creates temporary structures necessary for cell activity."One of the principal objects of theoretical research in any department of knowledge is to find the point of view from which the subject appears in its greatest simplicity."Josiah Willard Gibbs (1839-1903).

  7. Cellular immune response to β2-glycoprotein-I valine/leucine247 phenotypes in Mexican patients with primary antiphospholipid syndrome.

    PubMed

    Núñez-Álvarez, Carlos A; Hernández-Ramírez, Diego F; Martinez-Castillo, Araceli; Pascual Ramos, Virginia; Cabiedes, Javier; Ortega, Alicia; Cabral, Antonio R

    2017-02-01

    Homozygote genotype V 247 of the β 2 -glycoprotein-I (β 2 GP-I) gene has been associated with anti-β 2 GP-I and thrombosis in patients with primary anti-phospholipid syndrome APS (PAPS). However, the cellular immune response to β 2 GP-I 247 has been little studied. To evaluate the immune cellular proliferation in response to native and non-native β 2 GP-I 247 valine/leucine phenotype from Mexican patients with PAPS. We studied 10 patients with PAPS and 10 healthy control subjects (HC). The polymorphism at position 247 of the β 2 GP-I gene was determined by PCR-RFLP and the corresponding β 2 GP-I protein was subsequently purified from normal human plasma by affinity chromatography. PBMC purified from patients and controls were stimulated with β 2 GP-I under native and in non native (reduced) conditions. We also determined the anti-β 2 GP-I production in vitro by B cell clones (EBV) generated in cocultures experiments. Differential Scanning Calorimetry (DSC) was studied to determine the structural differences between the β 2 GP-I 247 valine/leucine isoforms. Cytokine profile (IL-2, IL-4, IL-6, TNFα, INFγ) was evaluated in culture supernatants. PAPS and healthy control PBMCs had a higher proliferative response when stimulated with β 2 GP-I under reduced cultures conditions compared to non-denatured conditions. PBMCs response from PAPS patients was higher. We observed more cell proliferation in response to β 2 GP-I 247 valine/leucine or valine isoforms in non-native conditions. In contrast, this response was not significant against β 2 GP-I 247 leucine. These findings were T CD4 + -dependent. Similar results were obtained with B cell clones derived from PAPS patients, which showed more pronounced proliferation in non native conditions and higher against β 2 GP-I 247 valine. No differences were found in anti-β 2 GP-I production, but high levels of IL-6 in vitro were identified. The structural analysis of both β 2 GP-I 247 isoforms by DSC showed a major conformational change due to a single mutation in the β 2 GP-I variants. PAPS PBMCs had a higher cellular response against β 2 GP-I 247 in non-native culture conditions preferentially to the β 2 GP-I 247 valine phenotype. This effect is T CD4 + dependent and appears to be driven by tertiary structural changes adopted by β 2 GP-I 247 polymorphism. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  8. Critical Contexts for Biomedical Research in a Native American Community: Health Care, History, and Community Survival

    ERIC Educational Resources Information Center

    Sahota, Puneet Chawla

    2012-01-01

    Native Americans have been underrepresented in previous studies of biomedical research participants. This paper reports a qualitative interview study of Native Americans' perspectives on biomedical research. In-depth interviews were conducted with 53 members of a Southwest tribal community. Many interviewees viewed biomedical research studies as a…

  9. Reflecting on Native Speaker Privilege

    ERIC Educational Resources Information Center

    Berger, Kathleen

    2014-01-01

    The issues surrounding native speakers (NSs) and nonnative speakers (NNSs) as teachers (NESTs and NNESTs, respectively) in the field of teaching English to speakers of other languages (TESOL) are a current topic of interest. In many contexts, the native speaker of English is viewed as the model teacher, thus putting the NEST into a position of…

  10. Barriers to Professionalism in the Native-Speaking English Teacher Scheme in Hong Kong

    ERIC Educational Resources Information Center

    Moorhouse, Benjamin Luke

    2017-01-01

    This article reports on a small-scale exploratory study that examined how native-speaking English teachers (NETs) working in the Primary Native-speaking English Teacher (PNET) Scheme construct their professional identity(ies) and explored the barriers to their professionalism that exist within their role and context. Data were collected using…

  11. Re-Envisioning Literacy in a Teacher Inquiry Group in a Native American Context

    ERIC Educational Resources Information Center

    Vaughn, Margaret

    2016-01-01

    The present study describes a yearlong collaborative inquiry involving six teachers and their professional discussions about literacy instruction as they developed a curriculum to support the cultural and linguistic needs of their school's 88% Native American student population. Participants in this study were four Native American teachers and two…

  12. Multicompetence and Native Speaker Variation in Clausal Packaging in Japanese

    ERIC Educational Resources Information Center

    Brown, Amanda; Gullberg, Marianne

    2012-01-01

    Native speakers show systematic variation in a range of linguistic domains as a function of a variety of sociolinguistic variables. This article addresses native language variation in the context of multicompetence, i.e. knowledge of two languages in one mind (Cook, 1991). Descriptions of motion were elicited from functionally monolingual and…

  13. Indian Summer: A "Hands-On, Feet-Wet" Approach to Science Education.

    ERIC Educational Resources Information Center

    Galindo, Ed; Barta, Jim

    2001-01-01

    A summer fish recovery program along the Salmon River (Idaho) involves Native American high school students in science, technology, and research within a cultural and environmental context. The positive attitudes and work ethic of Native students and the research and study skills they acquired demonstrate that Native students succeed when their…

  14. Analysis of Alternative Pre-RNA Splicing in the Mouse Retina Using a Fluorescent Reporter.

    PubMed

    Murphy, Daniel; Kolandaivelu, Saravanan; Ramamurthy, Visvanathan; Stoilov, Peter

    2016-01-01

    In vivo alternative splicing is controlled in a tissue and cell type specific manner. Often individual cellular components of complex tissues will express different splicing programs. Thus, when studying splicing in multicellular organisms it is critical to determine the exon inclusion levels in individual cells positioned in the context of their native tissue or organ. Here we describe how a fluorescent splicing reporter in combination with in vivo electroporation can be used to visualize alternative splicing in individual cells within mature tissues. In a test case we show how the splicing of a photoreceptor specific exon can be visualized within the mouse retina. The retina was chosen as an example of a complex tissue that is fragile and whose cells cannot be studied in culture. With minor modifications to the injection and electroporation procedure, the protocol we outline can be applied to other tissues and organs.

  15. The phonotactic influence on the perception of a consonant cluster /pt/ by native English and native Polish listeners: A behavioral and event related potential (ERP) study

    PubMed Central

    Wagner, Monica; Shafer, Valerie L.; Martin, Brett; Steinschneider, Mitchell

    2013-01-01

    The effect of exposure to the contextual features of the /pt/ cluster was investigated in native-English and native-Polish listeners using behavioral and event-related potential (ERP) methodology. Both groups experience the /pt/ cluster in their languages, but only the Polish group experiences the cluster in the context of word onset examined in the current experiment. The /st/ cluster was used as an experimental control. ERPs were recorded while participants identified the number of syllables in the second word of nonsense word pairs. The results found that only Polish listeners accurately perceived the /pt/ cluster and perception was reflected within a late positive component of the ERP waveform. Furthermore, evidence of discrimination of /pt/ and /pǝt/ onsets in the neural signal was found even for non-native listeners who could not perceive the difference. These findings suggest that exposure to phoneme sequences in highly specific contexts may be necessary for accurate perception. PMID:22867752

  16. Adaptation of Consultation Planning for Native American and Latina Women with Breast Cancer

    ERIC Educational Resources Information Center

    Belkora, Jeffrey; Franklin, Lauren; O'Donnell, Sara; Ohnemus, Julie; Stacey, Dawn

    2009-01-01

    Context: Resource centers in rural, underserved areas are implementing Consultation Planning (CP) to help women with breast cancer create a question list before a doctor visit. Purpose: To identify changes needed for acceptable delivery of CP to rural Native Americans and Latinas. Methods: We interviewed and surveyed 27 Native American and Latino…

  17. Literacy Achievement of Children with Intellectual Disabilities and Differing Linguistic Backgrounds

    ERIC Educational Resources Information Center

    Verhoeven, L.; Vermeer, A.

    2006-01-01

    Background: The aim of the present study was to examine the literacy achievement of 10- to 12-year-old native and non-native children with intellectual disabilities (ID) living in the Netherlands. An intriguing question within this context was whether the second language learning non-native children with ID would show a double disadvantage when…

  18. Perceptions of Stress among Native American and Hispanic K-5 Teachers

    ERIC Educational Resources Information Center

    Lotz-Drlik, Jane Elizabeth

    2012-01-01

    Within the context of a nationwide shortage of teachers of color, stable enrollment of Native American students, and increasing enrollments of Hispanic students, the purpose of this study was to examine self-reported stress among Native American, Hispanic, and Caucasian K-5 teachers. This was a mixed-methods study, with both quantitative and…

  19. The Effects of Language Experience and Speech Context on the Phonetic Accommodation of English-accented Spanish Voicing.

    PubMed

    Llanos, Fernando; Francis, Alexander L

    2017-03-01

    Native speakers of Spanish with different amounts of experience with English classified stop-consonant voicing (/b/ versus /p/) across different speech accents: English-accented Spanish, native Spanish, and native English. While listeners with little experience with English classified target voicing with an English- or Spanish-like voice onset time (VOT) boundary, predicted by contextual VOT, listeners familiar with English relied on an English-like VOT boundary in an English-accented Spanish context even in the absence of clear contextual cues to English VOT. This indicates that Spanish listeners accommodated English-accented Spanish voicing differently depending on their degree of familiarization with the English norm.

  20. Cytoplasmically Retargeted HSV1-tk/GFP Reporter Gene Mutants for Optimization of Noninvasive Molecular-Genetic Imaging

    PubMed Central

    Ponomarev, Vladimir; Doubrovin, Michael; Serganova, Inna; Beresten, Tatiana; Vider, Jelena; Shavrin, Aleksander; Ageyeva, Ludmila; Balatoni, Julius; Blasberg, Ronald; Tjuvajev, Juri Gelovani

    2003-01-01

    Abstract To optimize the sensitivity of imaging HSV1-tk/GFP reporter gene expression, a series of HSV1-tk/GFP mutants was developed with altered nuclear localization and better cellular enzymatic activity, compared to that of the native HSV1-tk/GFP fusion protein (HSV1-tk/GFP). Several modifications of HSV1-tk/GFP reporter gene were performed, including targeted inactivating mutations in the nuclear localization signal (NLS), the addition of a nuclear export signal (NES), a combination of both mutation types, and a truncation of the first 135 bp of the native hsv1-tk coding sequence containing a “cryptic” testicular promoter and the NLS. A recombinant HSV1-tk/GFP protein and a highly sensitive sandwich enzyme-linked immunosorbent assay for HSV1-tk/GFP were developed to quantitate the amount of reporter gene product in different assays to allow normalization of the data. These different mutations resulted in various degrees of nuclear clearance, predominant cytoplasmic distribution, and increased total cellular enzymatic activity of the HSV1-tk/GFP mutants, compared to native HSV1-tk/GFP when expressed at the same levels. This appears to be the result of improvedmetabolic bioavailability of cytoplasmically retargeted mutant HSV1-tk/GFP enzymes for reaction with the radiolabeled probe (e.g., FIAU). The analysis of enzymatic properties of different HSV1-tk/GFP mutants using FIAU as a substrate revealed no significant differences from that of the native HSV1-tk/GFP. Improved total cellular enzymatic activity of cytoplasmically retargeted HSV1-tk/GFP mutants observed in vitro was confirmed by noninvasive imaging of transduced subcutaneous tumor xenografts bearing these reporters using [131I]FIAU and a γ-camera. PMID:12869307

  1. Native American Historic Context for the United States Military Academy, West Point, New York

    DTIC Science & Technology

    2006-04-01

    Native Americans in the Hudson Highlands Pre-Contact Period A number of American Indian nations have over time either occupied the Hudson Valley...inability of Western legal institutions to grasp American Indian and Alaska Native claims that some places on the planet possess a degree of...archeological sites near the USMA. It contains a brief history of various Native American nations that may have been living in or using the West Point

  2. "Borrowing" Activities from Another Culture: A Native American's Perspective.

    ERIC Educational Resources Information Center

    Oles, Gordon W. A.

    1992-01-01

    Criticizes the practice in adventure education of using Native American rituals and practices without the proper cultural context. Suggests that western society uses rites and ceremonies initiated in its own culture for experiential education. (KS)

  3. On the Englishes Used in Written Business Communications across Cultures: Can Readers Tell the Difference? And Does It Matter?

    ERIC Educational Resources Information Center

    Frank, Jane

    A pilot study investigated the varieties of English used in two commercial contexts and the success of speakers from different cultural and linguistic backgrounds in transmitting intended information to listeners from other native language backgrounds. A questionnaire was administered to both native speakers of English (NS) and non-native speakers…

  4. Culture and Educational Policy in Hawai'i: The Silencing of Native Voices. Sociocultural, Political, and Historical Studies in Education.

    ERIC Educational Resources Information Center

    Benham, Maenette K. P. Ah Nee; Heck, Ronald H.

    This book provides a critical assessment of Native Hawaiian education. It focuses on the historical, political, and cultural contexts producing institutionalized structures that kept Hawaiians marginalized in the schools and wider society. It also looks at current attempts of Native Hawaiians to reclaim a part of their lands and self-determination…

  5. Songbird abundance in native and planted grassland varies with type and amount of grassland in the surrounding landscape

    USGS Publications Warehouse

    Davis, Stephen K.; Fisher, Ryan; Skinner, Susan; Shaffer, Terry L.; Brigham, R. Mark

    2013-01-01

    Agriculture and wildlife conservation programs have converted vast amounts of cropland into grasslands planted with exotic species. Understanding how landscape context influences avian use of native and planted grasslands is essential for developing effective conservation strategies in agricultural landscapes. Our primary objective was to determine the extent to which the amount and type of grassland in the surrounding landscape influences the abundance of grassland songbird species on native and planted grassland parcels in southern Saskatchewan and Alberta, Canada. Bird abundance was more strongly influenced by the amount and type of grassland within 400 m of breeding parcels than at larger spatial scales. Grassland specialists responded similarly to habitat and landscape type over both years and provinces. Sprague's pipit (Anthus spragueii) and Baird's sparrow (Ammodramus bairdii) were most common in native grassland parcels surrounded by native grassland and were more likely to occur in planted grasslands surrounded by native grassland. Bobolinks (Dolichonyx oryzivorus) were most common in planted grassland parcels, but their abundance increased with the amount of native grassland surrounding these parcels. Our findings indicate that the suitability of planted grasslands for these species is influenced by their proximity to native grassland. Grassland generalists showed mixed responses to habitat and landscape type over the 2 years (Le Conte's sparrow [Ammodramus leconteii]) and between provinces (Savannah sparrow [Passerculus sandwichensis] and western meadowlark [Sturnella neglecta]). Management to benefit grassland specialists should therefore consider the landscape context when seeding cultivated land to non-native grassland and conserve extant native grassland.

  6. Protein structure in context: The molecular landscape of angiogenesis

    PubMed Central

    Span, Elise A.; Goodsell, David S.; Ramchandran, Ramani; Franzen, Margaret; Herman, Timothy; Sem, Daniel S.

    2014-01-01

    A team of students, educators, and researchers has developed new materials to teach cell signaling within its cellular context. Two non-traditional modalities are employed: physical models, to explore the atomic details of several of the proteins in the angiogenesis signaling cascade, and illustrations of the proteins in their cellular environment, to give an intuitive understanding of the cellular context of the pathway. The experiences of the team underscore the utility of these types of materials as an effective mode for fostering students’ understanding of the molecular world, and the scientific method used to define it. PMID:23868376

  7. Reconceptualizing Native Women's Health: An “Indigenist” Stress-Coping Model

    PubMed Central

    Walters, Karina L.; Simoni, Jane M.

    2002-01-01

    This commentary presents an “indigenist” model of Native women's health, a stress-coping paradigm that situates Native women's health within the larger context of their status as a colonized people. The model is grounded in empirical evidence that traumas such as the “soul wound” of historical and contemporary discrimination among Native women influence health and mental health outcomes. The preliminary model also incorporates cultural resilience, including as moderators identity, enculturation, spiritual coping, and traditional healing practices. Current epidemiological data on Native women's general health and mental health are reconsidered within the framework of this model. PMID:11919043

  8. EFL Learners' Beliefs about Native and Non-Native English-Speaking Teachers: Perceived Strengths, Weaknesses, and Preferences

    ERIC Educational Resources Information Center

    Chun, Sun Young

    2014-01-01

    Although the number of native English-speaking teachers (NESTs) in English as a Foreign Language (EFL) contexts has increased in recent years with the emergence of English as an international language, only a few studies on NESTs and non-NESTs have extensively and directly examined students' beliefs about these two groups of teachers. To fill this…

  9. Responses of Plant Proteins to Heavy Metal Stress—A Review

    PubMed Central

    Hasan, Md. Kamrul; Cheng, Yuan; Kanwar, Mukesh K.; Chu, Xian-Yao; Ahammed, Golam J.; Qi, Zhen-Yu

    2017-01-01

    Plants respond to environmental pollutants such as heavy metal(s) by triggering the expression of genes that encode proteins involved in stress response. Toxic metal ions profoundly affect the cellular protein homeostasis by interfering with the folding process and aggregation of nascent or non-native proteins leading to decreased cell viability. However, plants possess a range of ubiquitous cellular surveillance systems that enable them to efficiently detoxify heavy metals toward enhanced tolerance to metal stress. As proteins constitute the major workhorses of living cells, the chelation of metal ions in cytosol with phytochelatins and metallothioneins followed by compartmentalization of metals in the vacuoles as well as the repair of stress-damaged proteins or removal and degradation of proteins that fail to achieve their native conformations are critical for plant tolerance to heavy metal stress. In this review, we provide a broad overview of recent advances in cellular protein research with regards to heavy metal tolerance in plants. We also discuss how plants maintain functional and healthy proteomes for survival under such capricious surroundings. PMID:28928754

  10. Native American Education.

    ERIC Educational Resources Information Center

    Mueller, Jean West; Schamel, Wynell Burroughs

    1990-01-01

    Examines an 1876 letter from a missionary to Ferdinand V. Hayden in the context of the U.S. government's policy of instituting religious education and training for Native Americans. Provides a photocopy of the letter and outlines class activities designed to help students analyze the document. (DB)

  11. Predicting invasive species impacts: a community module functional response approach reveals context dependencies.

    PubMed

    Paterson, Rachel A; Dick, Jaimie T A; Pritchard, Daniel W; Ennis, Marilyn; Hatcher, Melanie J; Dunn, Alison M

    2015-03-01

    Predatory functional responses play integral roles in predator-prey dynamics, and their assessment promises greater understanding and prediction of the predatory impacts of invasive species. Other interspecific interactions, however, such as parasitism and higher-order predation, have the potential to modify predator-prey interactions and thus the predictive capability of the comparative functional response approach. We used a four-species community module (higher-order predator; focal native or invasive predators; parasites of focal predators; native prey) to compare the predatory functional responses of native Gammarus duebeni celticus and invasive Gammarus pulex amphipods towards three invertebrate prey species (Asellus aquaticus, Simulium spp., Baetis rhodani), thus, quantifying the context dependencies of parasitism and a higher-order fish predator on these functional responses. Our functional response experiments demonstrated that the invasive amphipod had a higher predatory impact (lower handling time) on two of three prey species, which reflects patterns of impact observed in the field. The community module also revealed that parasitism had context-dependent influences, for one prey species, with the potential to further reduce the predatory impact of the invasive amphipod or increase the predatory impact of the native amphipod in the presence of a higher-order fish predator. Partial consumption of prey was similar for both predators and occurred increasingly in the order A. aquaticus, Simulium spp. and B. rhodani. This was associated with increasing prey densities, but showed no context dependencies with parasitism or higher-order fish predator. This study supports the applicability of comparative functional responses as a tool to predict and assess invasive species impacts incorporating multiple context dependencies. © 2014 The Authors. Journal of Animal Ecology © 2014 British Ecological Society.

  12. Raspberry, not a car: context predictability and a phonological advantage in early and late learners’ processing of speech in noise

    PubMed Central

    Gor, Kira

    2014-01-01

    Second language learners perform worse than native speakers under adverse listening conditions, such as speech in noise (SPIN). No data are available on heritage language speakers’ (early naturalistic interrupted learners’) ability to perceive SPIN. The current study fills this gap and investigates the perception of Russian speech in multi-talker babble noise by the matched groups of high- and low-proficiency heritage speakers (HSs) and late second language learners of Russian who were native speakers of English. The study includes a control group of Russian native speakers. It manipulates the noise level (high and low), and context cloze probability (high and low). The results of the SPIN task are compared to the tasks testing the control of phonology, AXB discrimination and picture-word discrimination, and lexical knowledge, a word translation task, in the same participants. The increased phonological sensitivity of HSs interacted with their ability to rely on top–down processing in sentence integration, use contextual cues, and build expectancies in the high-noise/high-context condition in a bootstrapping fashion. HSs outperformed oral proficiency-matched late second language learners on SPIN task and two tests of phonological sensitivity. The outcomes of the SPIN experiment support both the early naturalistic advantage and the role of proficiency in HSs. HSs’ ability to take advantage of the high-predictability context in the high-noise condition was mitigated by their level of proficiency. Only high-proficiency HSs, but not any other non-native group, took advantage of the high-predictability context that became available with better phonological processing skills in high-noise. The study thus confirms high-proficiency (but not low-proficiency) HSs’ nativelike ability to combine bottom–up and top–down cues in processing SPIN. PMID:25566130

  13. Raspberry, not a car: context predictability and a phonological advantage in early and late learners' processing of speech in noise.

    PubMed

    Gor, Kira

    2014-01-01

    Second language learners perform worse than native speakers under adverse listening conditions, such as speech in noise (SPIN). No data are available on heritage language speakers' (early naturalistic interrupted learners') ability to perceive SPIN. The current study fills this gap and investigates the perception of Russian speech in multi-talker babble noise by the matched groups of high- and low-proficiency heritage speakers (HSs) and late second language learners of Russian who were native speakers of English. The study includes a control group of Russian native speakers. It manipulates the noise level (high and low), and context cloze probability (high and low). The results of the SPIN task are compared to the tasks testing the control of phonology, AXB discrimination and picture-word discrimination, and lexical knowledge, a word translation task, in the same participants. The increased phonological sensitivity of HSs interacted with their ability to rely on top-down processing in sentence integration, use contextual cues, and build expectancies in the high-noise/high-context condition in a bootstrapping fashion. HSs outperformed oral proficiency-matched late second language learners on SPIN task and two tests of phonological sensitivity. The outcomes of the SPIN experiment support both the early naturalistic advantage and the role of proficiency in HSs. HSs' ability to take advantage of the high-predictability context in the high-noise condition was mitigated by their level of proficiency. Only high-proficiency HSs, but not any other non-native group, took advantage of the high-predictability context that became available with better phonological processing skills in high-noise. The study thus confirms high-proficiency (but not low-proficiency) HSs' nativelike ability to combine bottom-up and top-down cues in processing SPIN.

  14. Cellular context-dependent consequences of Apc mutations on gene regulation and cellular behavior.

    PubMed

    Hashimoto, Kyoichi; Yamada, Yosuke; Semi, Katsunori; Yagi, Masaki; Tanaka, Akito; Itakura, Fumiaki; Aoki, Hitomi; Kunisada, Takahiro; Woltjen, Knut; Haga, Hironori; Sakai, Yoshiharu; Yamamoto, Takuya; Yamada, Yasuhiro

    2017-01-24

    The spectrum of genetic mutations differs among cancers in different organs, implying a cellular context-dependent effect for genetic aberrations. However, the extent to which the cellular context affects the consequences of oncogenic mutations remains to be fully elucidated. We reprogrammed colon tumor cells in an Apc Min/+ (adenomatous polyposis coli) mouse model, in which the loss of the Apc gene plays a critical role in tumor development and subsequently, established reprogrammed tumor cells (RTCs) that exhibit pluripotent stem cell (PSC)-like signatures of gene expression. We show that the majority of the genes in RTCs that were affected by Apc mutations did not overlap with the genes affected in the intestine. RTCs lacked pluripotency but exhibited an increased expression of Cdx2 and a differentiation propensity that was biased toward the trophectoderm cell lineage. Genetic rescue of the mutated Apc allele conferred pluripotency on RTCs and enabled their differentiation into various cell types in vivo. The redisruption of Apc in RTC-derived differentiated cells resulted in neoplastic growth that was exclusive to the intestine, but the majority of the intestinal lesions remained as pretumoral microadenomas. These results highlight the significant influence of cellular context on gene regulation, cellular plasticity, and cellular behavior in response to the loss of the Apc function. Our results also imply that the transition from microadenomas to macroscopic tumors is reprogrammable, which underscores the importance of epigenetic regulation on tumor promotion.

  15. Cellular context-dependent consequences of Apc mutations on gene regulation and cellular behavior

    PubMed Central

    Hashimoto, Kyoichi; Yamada, Yosuke; Semi, Katsunori; Yagi, Masaki; Tanaka, Akito; Itakura, Fumiaki; Aoki, Hitomi; Kunisada, Takahiro; Woltjen, Knut; Haga, Hironori; Sakai, Yoshiharu; Yamamoto, Takuya; Yamada, Yasuhiro

    2017-01-01

    The spectrum of genetic mutations differs among cancers in different organs, implying a cellular context-dependent effect for genetic aberrations. However, the extent to which the cellular context affects the consequences of oncogenic mutations remains to be fully elucidated. We reprogrammed colon tumor cells in an ApcMin/+ (adenomatous polyposis coli) mouse model, in which the loss of the Apc gene plays a critical role in tumor development and subsequently, established reprogrammed tumor cells (RTCs) that exhibit pluripotent stem cell (PSC)-like signatures of gene expression. We show that the majority of the genes in RTCs that were affected by Apc mutations did not overlap with the genes affected in the intestine. RTCs lacked pluripotency but exhibited an increased expression of Cdx2 and a differentiation propensity that was biased toward the trophectoderm cell lineage. Genetic rescue of the mutated Apc allele conferred pluripotency on RTCs and enabled their differentiation into various cell types in vivo. The redisruption of Apc in RTC-derived differentiated cells resulted in neoplastic growth that was exclusive to the intestine, but the majority of the intestinal lesions remained as pretumoral microadenomas. These results highlight the significant influence of cellular context on gene regulation, cellular plasticity, and cellular behavior in response to the loss of the Apc function. Our results also imply that the transition from microadenomas to macroscopic tumors is reprogrammable, which underscores the importance of epigenetic regulation on tumor promotion. PMID:28057861

  16. MNF, an ankyrin repeat protein of myxoma virus, is part of a native cellular SCF complex during viral infection

    PubMed Central

    2010-01-01

    Myxoma virus (MYXV), a member of the Poxviridae family, is the agent responsible for myxomatosis, a fatal disease in the European rabbit (Oryctolagus cuniculus). Like all poxviruses, MYXV is known for encoding multiple proteins that regulate cellular signaling pathways. Among them, four proteins share the same ANK/PRANC structure: M148R, M149R, MNF (Myxoma Nuclear factor) and M-T5, all of them described as virulence factors. This family of poxvirus proteins, recently identified, has drawn considerable attention for its potential role in modulating the host ubiquitin-proteasome system during viral infection. To date, many members of this novel protein family have been shown to interact with SCF components, in vitro. Here, we focus on MNF gene, which has been shown to express a nuclear protein presenting nine ANK repeats, one of which has been identified as a nuclear localization signal. In transfection, MNF has been shown to colocalise with the transcription factor NF-κB in the nucleus of TNFα-stimulated cells. Functionally, MNF is a critical virulence factor since its deletion generates an almost apathogenic virus. In this study, to pursue the investigation of proteins interacting with MNF and of its mechanism of action, we engineered a recombinant MYXV expressing a GFP-linked MNF under the control of MNF native promoter. Infection of rabbits with MYXV-GFPMNF recombinant virus provided the evidence that the GFP fusion does not disturb the main function of MNF. Hence, cells were infected with MYXV-GFPMNF and immunoprecipitation of the GFPMNF fusion protein was performed to identify MNF's partners. For the first time, endogenous components of SCF (Cullin-1 and Skp1) were co-precipitated with an ANK myxoma virus protein, expressed in an infectious context, and without over-expression of any protein. PMID:20211013

  17. The Way of the Human Being: Supporting Alaska Native Families Who Have a Child with a Disability

    ERIC Educational Resources Information Center

    Ryan, Susan; Murphy, Blanche; Harvey, Sandra; Nygren, Kristin; Kinavey, Erin; Ongtooguk, Paul

    2006-01-01

    Alaska Native peoples refer to themselves and their way of life as the "way of the human being" (Napolean, 1991). This term, referred to as "Yuuyaraq" by the Yup'ik Eskimo, speaks to the value the Yup'ik and other Alaskan Natives place on being fully human. Within the context of the "way of the human life," how can…

  18. Use of Media Technologies by Native American Teens and Young Adults: Evaluating Their Utility for Designing Culturally-Appropriate Sexual Health Interventions Targeting Native Youth in the Pacific Northwest

    ERIC Educational Resources Information Center

    Craig Rushing, Stephanie Nicole

    2010-01-01

    American Indian and Alaska Native (AI/AN) youth are disproportionally burdened by high rates of sexually transmitted infections and teen pregnancy, heightening their need for sexual health interventions that are aligned to their unique culture and social context. Media technologies, including the Internet, cell phones, and video games, offer new…

  19. Insights from a Learner Corpus as Opposed to a Native Corpus about Cohesive Devices in an Academic Writing Context

    ERIC Educational Resources Information Center

    Ersanli, Ceylan Yangin

    2015-01-01

    This study reports on the insights from an EFL learner corpora (a total of 151 essays and 49,690 words) generated from essays collected over the years in a Turkish state university from freshmen students enrolling in the Advanced Writing course. The comparison of cohesive devices in the non-native corpus (NNC) with those in a native corpus (NC)…

  20. Hemispheric asymmetry of emotion words in a non-native mind: a divided visual field study.

    PubMed

    Jończyk, Rafał

    2015-05-01

    This study investigates hemispheric specialization for emotional words among proficient non-native speakers of English by means of the divided visual field paradigm. The motivation behind the study is to extend the monolingual hemifield research to the non-native context and see how emotion words are processed in a non-native mind. Sixty eight females participated in the study, all highly proficient in English. The stimuli comprised 12 positive nouns, 12 negative nouns, 12 non-emotional nouns and 36 pseudo-words. To examine the lateralization of emotion, stimuli were presented unilaterally in a random fashion for 180 ms in a go/no-go lexical decision task. The perceptual data showed a right hemispheric advantage for processing speed of negative words and a complementary role of the two hemispheres in the recognition accuracy of experimental stimuli. The data indicate that processing of emotion words in non-native language may require greater interhemispheric communication, but at the same time demonstrates a specific role of the right hemisphere in the processing of negative relative to positive valence. The results of the study are discussed in light of the methodological inconsistencies in the hemifield research as well as the non-native context in which the study was conducted.

  1. Discourse comprehension in L2: Making sense of what is not explicitly said.

    PubMed

    Foucart, Alice; Romero-Rivas, Carlos; Gort, Bernharda Lottie; Costa, Albert

    2016-12-01

    Using ERPs, we tested whether L2 speakers can integrate multiple sources of information (e.g., semantic, pragmatic information) during discourse comprehension. We presented native speakers and L2 speakers with three-sentence scenarios in which the final sentence was highly causally related, intermediately related, or causally unrelated to its context; its interpretation therefore required simple or complex inferences. Native speakers revealed a gradual N400-like effect, larger in the causally unrelated condition than in the highly related condition, and falling in-between in the intermediately related condition, replicating previous results. In the crucial intermediately related condition, L2 speakers behaved like native speakers, however, showing extra processing in a later time-window. Overall, the results show that, when reading, L2 speakers are able to process information from the local context and prior information (e.g., world knowledge) to build global coherence, suggesting that they process different sources of information to make inferences online during discourse comprehension, like native speakers. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Preventing α-synuclein aggregation: the role of the small heat-shock molecular chaperone proteins.

    PubMed

    Cox, Dezerae; Carver, John A; Ecroyd, Heath

    2014-09-01

    Protein homeostasis, or proteostasis, is the process of maintaining the conformational and functional integrity of the proteome. The failure of proteostasis can result in the accumulation of non-native proteins leading to their aggregation and deposition in cells and in tissues. The amyloid fibrillar aggregation of the protein α-synuclein into Lewy bodies and Lewy neuritis is associated with neurodegenerative diseases classified as α-synucleinopathies, which include Parkinson's disease and dementia with Lewy bodies. The small heat-shock proteins (sHsps) are molecular chaperones that are one of the cell's first lines of defence against protein aggregation. They act to stabilise partially folded protein intermediates, in an ATP-independent manner, to maintain cellular proteostasis under stress conditions. Thus, the sHsps appear ideally suited to protect against α-synuclein aggregation, yet these fail to do so in the context of the α-synucleinopathies. This review discusses how sHsps interact with α-synuclein to prevent its aggregation and, in doing so, highlights the multi-faceted nature of the mechanisms used by sHsps to prevent the fibrillar aggregation of proteins. It also examines what factors may contribute to α-synuclein escaping the sHsp chaperones in the context of the α-synucleinopathies. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  3. Native Speakers in Linguistic Imperialism

    ERIC Educational Resources Information Center

    Phillipson, Robert

    2016-01-01

    An investigation of Native English Speaking Teachers' performance in schemes in six Asian contexts, commissioned by the British Council, and undertaken by three British academics, is subjected to critical evaluation. Key issues for exploration are the issue of a monolingual approach to English learning and teaching, and the inappropriate…

  4. English as Cultural Action.

    ERIC Educational Resources Information Center

    Prodromou, Luke

    1988-01-01

    Discusses teaching and learning English as a foreign language in its cultural context, and the culture of the native speaker of English and its relation to the culture of the learner. Native-speaking teachers should recognize the international status of English and work from local varieties of the language. (Author/LMO)

  5. The Acquisition of English Focus Marking by Non-Native Speakers

    NASA Astrophysics Data System (ADS)

    Baker, Rachel Elizabeth

    This dissertation examines Mandarin and Korean speakers' acquisition of English focus marking, which is realized by accenting particular words within a focused constituent. It is important for non-native speakers to learn how accent placement relates to focus in English because appropriate accent placement and realization makes a learner's English more native-like and easier to understand. Such knowledge may also improve their English comprehension skills. In this study, 20 native English speakers, 20 native Mandarin speakers, and 20 native Korean speakers participated in four experiments: (1) a production experiment, in which they were recorded reading the answers to questions, (2) a perception experiment, in which they were asked to determine which word in a recording was the last prominent word, (3) an understanding experiment, in which they were asked whether the answers in recorded question-answer pairs had context-appropriate prosody, and (4) an accent placement experiment, in which they were asked which word they would make prominent in a particular context. Finally, a new group of native English speakers listened to utterances produced in the production experiment, and determined whether the prosody of each utterance was appropriate for its context. The results of the five experiments support a novel predictive model for second language prosodic focus marking acquisition. This model holds that both transfer of linguistic features from a learner's native language (L1) and features of their second language (L2) affect learners' acquisition of prosodic focus marking. As a result, the model includes two complementary components: the Transfer Component and the L2 Challenge Component. The Transfer Component predicts that prosodic structures in the L2 will be more easily acquired by language learners that have similar structures in their L1 than those who do not, even if there are differences between the L1 and L2 in how the structures are realized. The L2 Challenge Component predicts that for difficult tasks, language learners will rely on widely-applied prosodic patterns, making them more successful at prosodically marking broad focus than narrow focus. However, for easy tasks, language learners will more successfully mark information structures that have a more direct relationship between focus and accent placement.

  6. Superresolution intrinsic fluorescence imaging of chromatin utilizing native, unmodified nucleic acids for contrast

    PubMed Central

    Dong, Biqin; Almassalha, Luay M.; Stypula-Cyrus, Yolanda; Urban, Ben E.; Chandler, John E.; Nguyen, The-Quyen; Sun, Cheng; Zhang, Hao F.; Backman, Vadim

    2016-01-01

    Visualizing the nanoscale intracellular structures formed by nucleic acids, such as chromatin, in nonperturbed, structurally and dynamically complex cellular systems, will help expand our understanding of biological processes and open the next frontier for biological discovery. Traditional superresolution techniques to visualize subdiffractional macromolecular structures formed by nucleic acids require exogenous labels that may perturb cell function and change the very molecular processes they intend to study, especially at the extremely high label densities required for superresolution. However, despite tremendous interest and demonstrated need, label-free optical superresolution imaging of nucleotide topology under native nonperturbing conditions has never been possible. Here we investigate a photoswitching process of native nucleotides and present the demonstration of subdiffraction-resolution imaging of cellular structures using intrinsic contrast from unmodified DNA based on the principle of single-molecule photon localization microscopy (PLM). Using DNA-PLM, we achieved nanoscopic imaging of interphase nuclei and mitotic chromosomes, allowing a quantitative analysis of the DNA occupancy level and a subdiffractional analysis of the chromosomal organization. This study may pave a new way for label-free superresolution nanoscopic imaging of macromolecular structures with nucleotide topologies and could contribute to the development of new DNA-based contrast agents for superresolution imaging. PMID:27535934

  7. Insights into nuclear dynamics using live-cell imaging approaches.

    PubMed

    Bigley, Rachel B; Payumo, Alexander Y; Alexander, Jeffrey M; Huang, Guo N

    2017-03-01

    The nucleus contains the genetic blueprint of the cell and myriad interactions within this subcellular structure are required for gene regulation. In the current scientific era, characterization of these gene regulatory networks through biochemical techniques coupled with systems-wide 'omic' approaches has become commonplace. However, these strategies are limited because they represent a mere snapshot of the cellular state. To obtain a holistic understanding of nuclear dynamics, relevant molecules must be studied in their native contexts in living systems. Live-cell imaging approaches are capable of providing quantitative assessment of the dynamics of gene regulatory interactions within the nucleus. We survey recent insights into what live-cell imaging approaches have provided the field of nuclear dynamics. In this review, we focus on interactions of DNA with other DNA loci, proteins, RNA, and the nuclear envelope. WIREs Syst Biol Med 2017, 9:e1372. doi: 10.1002/wsbm.1372 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

  8. Protein Structure in Context: The Molecular Landscape of Angiogenesis

    ERIC Educational Resources Information Center

    Span, Elise A.; Goodsell, David S.; Ramchandran, Ramani; Franzen, Margaret A.; Herman, Tim; Sem, Daniel S.

    2013-01-01

    A team of students, educators, and researchers has developed new materials to teach cell signaling within its cellular context. Two nontraditional modalities are employed: physical models, to explore the atomic details of several of the proteins in the angiogenesis signaling cascade, and illustrations of the proteins in their cellular environment,…

  9. Modelling biological invasions: species traits, species interactions, and habitat heterogeneity.

    PubMed

    Cannas, Sergio A; Marco, Diana E; Páez, Sergio A

    2003-05-01

    In this paper we explore the integration of different factors to understand, predict and control ecological invasions, through a general cellular automaton model especially developed. The model includes life history traits of several species in a modular structure interacting multiple cellular automata. We performed simulations using field values corresponding to the exotic Gleditsia triacanthos and native co-dominant trees in a montane area. Presence of G. triacanthos juvenile bank was a determinant condition for invasion success. Main parameters influencing invasion velocity were mean seed dispersal distance and minimum reproductive age. Seed production had a small influence on the invasion velocity. Velocities predicted by the model agreed well with estimations from field data. Values of population density predicted matched field values closely. The modular structure of the model, the explicit interaction between the invader and the native species, and the simplicity of parameters and transition rules are novel features of the model.

  10. Broadening the Meaning of Citizenship Education: Native Americans and Tribal Nationhood

    ERIC Educational Resources Information Center

    Haynes Writer, Jeanette

    2010-01-01

    The reality of tribal nationhood and the dual citizenship that Native Americans carry in their tribal nations and the United States significantly expands the definition and parameters of citizen education. Citizenship education means including and understanding the historical and political contexts of all U.S. citizens--especially, those…

  11. The effect of recent competition between the native Anolis oculatus and the invasive A. cristatellus on display behavior.

    PubMed

    Dufour, Claire M S; Herrel, Anthony; Losos, Jonathan B

    2018-01-01

    Invasive species are a global threat to biodiversity. Cases where the invasion has been tracked since its beginning are rare, however, such that the first interactions between invasive and native species remain poorly understood. Communication behavior is an integral part of species identity and is subject to selection. Consequently, resource use and direct interference competition between native and invasive species may drive its evolution. Here, we tested the role of interactions between the recently introduced invasive lizard Anolis cristatellus and the native Anolis oculatus on variation in behavior and communication in Calibishie (Dominica). From May to June 2016, we filmed 122 adult males of both species displaying in banana farms under two contexts (allopatry and sympatry). We then recorded (i) the proportion of time spent displaying and (ii) the relative frequency of dewlap vs. push-up displays. To control for habitat variation, we measured and compared the habitat characteristics (canopy openness and habitat openness) of 228 males in allopatry and sympatry. While the habitat characteristics and total display-time did not differ between the contexts for the two species, the proportion of display-time spent dewlapping by A. cristatellus decreased in sympatry. The display of A. oculatus did not differ between the contexts, however. Shifts in microhabitat use, predation pressure, or interspecific interference are potential factors which might explain the behavioral changes in display observed in A. cristatellus . This study highlights the role of behavioral traits as a first response of an invasive species to recent competition with a closely related native species.

  12. Cell interactions in bone tissue engineering.

    PubMed

    Pirraco, R P; Marques, A P; Reis, R L

    2010-01-01

    Bone fractures, where the innate regenerative bone response is compromised, represent between 4 and 8 hundred thousands of the total fracture cases, just in the United States. Bone tissue engineering (TE) brought the notion that, in cases such as those, it was preferable to boost the healing process of bone tissue instead of just adding artificial parts that could never properly replace the native tissue. However, despite the hype, bone TE so far could not live up to its promises and new bottom-up approaches are needed. The study of the cellular interactions between the cells relevant for bone biology can be of essential importance to that. In living bone, cells are in a context where communication with adjacent cells is almost permanent. Many fundamental works have been addressing these communications nonetheless, in a bone TE approach, the 3D perspective, being part of the microenvironment of a bone cell, is as crucial. Works combining the study of cell-to-cell interactions in a 3D environment are not as many as expected. Therefore, the bone TE field should not only gain knowledge from the field of fundamental Biology but also contribute for further understanding the biology of bone. In this review, a summary of the main works in the field of bone TE, aiming at studying cellular interactions in a 3D environment, and how they contributed towards the development of a functional engineered bone tissue, is presented.

  13. 3D Printing Variable Stiffness Foams Using Viscous Thread Instability

    NASA Astrophysics Data System (ADS)

    Lipton, Jeffrey I.; Lipson, Hod

    2016-08-01

    Additive manufacturing of cellular structures has numerous applications ranging from fabrication of biological scaffolds and medical implants, to mechanical weight reduction and control over mechanical properties. Various additive manufacturing processes have been used to produce open regular cellular structures limited only by the resolution of the printer. These efforts have focused on printing explicitly designed cells or explicitly planning offsets between strands. Here we describe a technique for producing cellular structures implicitly by inducing viscous thread instability when extruding material. This process allows us to produce complex cellular structures at a scale that is finer than the native resolution of the printer. We demonstrate tunable effective elastic modulus and density that span two orders of magnitude. Fine grained cellular structures allow for fabrication of foams for use in a wide range of fields ranging from bioengineering, to robotics to food printing.

  14. Acculturation in Context: The Moderating Effects of Immigrant and Native Peer Orientations on the Acculturation Experiences of Immigrants.

    PubMed

    Titzmann, Peter F; Jugert, Philipp

    2015-11-01

    Immigrant adolescents have to navigate through a complex social environment consisting of, at least, both a native and a co-ethnic community. This study used a multi-level framework to consider two research questions involving this complexity. The individual-level associations of acculturation orientations and acculturative hassles (language and sociocultural adaptation) was assessed in immigrant youths, and whether this association differs depending on the school-level acculturation orientations held by co-ethnic peers, and the school-level orientations toward immigrants held by native German peers. We then investigated whether acculturative hassles are associated with the psychosocial functioning (self-efficacy, depressive symptoms) of immigrant adolescents. The sample comprised 650 ethnic German Diaspora migrant adolescents (mean age 15.6 years, 53.7 % female) and their 787 native German peers (mean age 15.05 years, 51 % female). The results showed that contextual factors (co-ethnic acculturation orientation, native friendship preferences) moderated the association between the acculturation orientations of adolescent immigrants and both types of acculturative hassles. Acculturative hassles, in turn, were associated with the psychosocial functioning of adolescents. This research demonstrates that a person-by-context perspective is needed to better understand the adaptation of adolescent immigrants. This perspective has to take into account both the native and the co-ethnic peer environment.

  15. Prospective Elementary Science Teachers' Understanding of Photosynthesis and Cellular Respiration in the Context of Multiple Biological Levels as Nested Systems

    ERIC Educational Resources Information Center

    Akçay, Süleyman

    2017-01-01

    In this study, Turkish prospective elementary science teachers' understanding of photosynthesis and cellular respiration has been analysed within the contexts of ecosystem knowledge, organism knowledge and interconnection knowledge (IK). In the analysis, concept maps developed by 74 prospective teachers were used. The study was carried out with…

  16. Matrix composition and mechanics of decellularized lung scaffolds.

    PubMed

    Petersen, Thomas H; Calle, Elizabeth A; Colehour, Maegen B; Niklason, Laura E

    2012-01-01

    The utility of decellularized native tissues for tissue engineering has been widely demonstrated. Here, we examine the production of decellularized lung scaffolds from native rodent lung using two different techniques, principally defined by use of either the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) or sodium dodecyl sulfate (SDS). All viable cellular material is removed, including at least 99% of DNA. Histochemical staining and mechanical testing indicate that collagen and elastin are retained in the decellularized matrices with CHAPS-based decellularization, while SDS-based decellularization leads to loss of collagen and decline in mechanical strength. Quantitative assays confirm that most collagen is retained with CHAPS treatment but that about 80% of collagen is lost with SDS treatment. In contrast, for both detergent methods, at least 60% of elastin content is lost along with about 95% of native proteoglycan content. Mechanical testing of the decellularized scaffolds indicates that they are mechanically similar to native lung using CHAPS decellularization, including retained tensile strength and elastic behavior, demonstrating the importance of collagen and elastin in lung mechanics. With SDS decellularization, the mechanical integrity of scaffolds is significantly diminished with some loss of elastic function as well. Finally, a simple theoretical model of peripheral lung matrix mechanics is consonant with our experimental findings. This work demonstrates the feasibility of producing a decellularized lung scaffold that can be used to study lung matrix biology and mechanics, independent of the effects of cellular components. Copyright © 2011 S. Karger AG, Basel.

  17. The Types and Effects of Peer Native Speakers' Feedback on CMC

    ERIC Educational Resources Information Center

    Diez-Bedmar, Maria Belen; Perez-Paredes, Pascual

    2012-01-01

    Online collaborative writing tasks are frequently undertaken in forums and wikis. Variation between these two communication modes has yet to be examined, particularly type of feedback and its effects. We investigated the type of feedback and the impact of English native-speakers' feedback on Spanish peers' discourse restructuring in the context of…

  18. Pausing, Preceding and Following "That" in English

    ERIC Educational Resources Information Center

    Bada, Erdogan

    2006-01-01

    While reading or speaking, individuals break up sentences into "meaningful chunks." This is true of any individual with any language background. Failure to do so, in an L2 context, leads to idiosyncrasies, and may possibly create some comprehensibility problems. In this study, native and non-native speakers of English read an authentic text into a…

  19. Evidence of biotic resistance to invasions in forests of the Eastern USA

    Treesearch

    Basil V. Iannone III; Kevin M. Potter; Kelly-Ann Dixon Hamil; Whitney Huang; Hao Zhang; Qinfeng Guo; Christopher M. Oswalt; Christopher W. Woodall; Songlin Fei

    2016-01-01

    Context Detecting biotic resistance to biological invasions across large geographic areas may require acknowledging multiple metrics of niche usage and potential spatial heterogeneity in associations between invasive and native species diversity and dominance.Objectives Determine (1) if native communities are ...

  20. Cultural Diversity and the Experiences of Alaska Native Nursing Students

    ERIC Educational Resources Information Center

    Gilmon, Margaret E.

    2012-01-01

    The purpose of this ethnonursing research study was to discover, describe, and systematically analyze the care expressions, practices, and patterns of Alaska Native nurses within the context of their nursing school experience. The goals of this study were to identify generic and professional care factors that promote the academic success of Alaska…

  1. Assessing Pronunciation in an EFL Context: Teachers' Orientations towards Nativeness and Intelligibility

    ERIC Educational Resources Information Center

    Bøhn, Henrik; Hansen, Thomas

    2017-01-01

    This study investigated EFL teachers' orientations toward the assessment of pronunciation at the upper-secondary school level in Norway. Data were gathered from purposeful samples of 24 interview informants and 46 questionnaire respondents. The teachers were asked about their attitudes toward the assessment of nativeness and intelligibility,…

  2. Politeness Strategies among Native and Romanian Speakers of English

    ERIC Educational Resources Information Center

    Ambrose, Dominic

    1995-01-01

    Background: Politeness strategies vary from language to language and within each society. At times the wrong strategies can have disastrous effects. This can occur when languages are used by non-native speakers or when they are used outside of their own home linguistic context. Purpose: This study of spoken language compares the politeness…

  3. Understanding Students' Epistemologies: Examining Practice and Meaning in Community Contexts

    ERIC Educational Resources Information Center

    Bang, Megan Elisabeth

    2009-01-01

    There is a great need to raise the levels of science achievement for those groups of children who have traditionally underperformed. Prior cognitive research with Native people suggests that problems with achievement for Native students may be more complicated then simple problems with knowing or not knowing content knowledge. This dissertation…

  4. Body Mass Index and Cancer Screening in Older American Indian and Alaska Native Men

    ERIC Educational Resources Information Center

    Muus, Kyle J.; Baker-Demaray, Twyla; McDonald, Leander R.; Ludtke, Richard L.; Allery, Alan J.; Bogart, T. Andy; Goldberg, Jack; Ramsey, Scott D.; Buchwald, Dedra S.

    2009-01-01

    Context: Regular screenings are important for reducing cancer morbidity and mortality. There are several barriers to receiving timely cancer screening, including overweight/obesity. No study has examined the relationship between overweight/obesity and cancer screening among American Indian/Alaska Natives (AI/ANs). Purpose: To describe the…

  5. Where do inmmigrants fare worse? Modeling workplace wage gap variation with longitudinal employer-employee data.

    PubMed

    Tomaskovic-Devey, Donald; Hällsten, Martin; Avent-Holt, Dustin

    2015-01-01

    The authors propose a strategy for observing and explaining workplace variance in categorically linked inequalities. Using Swedish economy-wide linked employer-employee panel data, the authors examine variation in workplace wage inequalities between native Swedes and non-Western immigrants. Consistent with relational inequality theory, the authors' findings are that immigrant-native wage gaps vary dramatically across workplaces, even net of strong human capital controls. The authors also find that, net of observed and fixed-effect controls for individual traits, workplace immigrant-native wage gaps decline with increased workplace immigrant employment and managerial representation and increase when job segregation rises. These results are stronger in high-inequality workplaces and for white-collar employees: contexts in which one expects status-based claims on organizational resources, the central causal mechanism identified by relational inequality theory, to be stronger. The authors conclude that workplace variation in the non-Western immigrant-native wage gaps is contingent on organizational variationin the relative power of groups and the institutional context in which that power is exercised.

  6. The Role of Auxiliary Subunits for the Functional Diversity of Voltage-Gated Calcium Channels

    PubMed Central

    Campiglio, Marta; Flucher, Bernhard E

    2015-01-01

    Voltage-gated calcium channels (VGCCs) represent the sole mechanism to convert membrane depolarization into cellular functions like secretion, contraction, or gene regulation. VGCCs consist of a pore-forming α1 subunit and several auxiliary channel subunits. These subunits come in multiple isoforms and splice-variants giving rise to a stunning molecular diversity of possible subunit combinations. It is generally believed that specific auxiliary subunits differentially regulate the channels and thereby contribute to the great functional diversity of VGCCs. If auxiliary subunits can associate and dissociate from pre-existing channel complexes, this would allow dynamic regulation of channel properties. However, most auxiliary subunits modulate current properties very similarly, and proof that any cellular calcium channel function is indeed modulated by the physiological exchange of auxiliary subunits is still lacking. In this review we summarize available information supporting a differential modulation of calcium channel functions by exchange of auxiliary subunits, as well as experimental evidence in support of alternative functions of the auxiliary subunits. At the heart of the discussion is the concept that, in their native environment, VGCCs function in the context of macromolecular signaling complexes and that the auxiliary subunits help to orchestrate the diverse protein–protein interactions found in these calcium channel signalosomes. Thus, in addition to a putative differential modulation of current properties, differential subcellular targeting properties and differential protein–protein interactions of the auxiliary subunits may explain the need for their vast molecular diversity. J. Cell. Physiol. 999: 00–00, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. J. Cell. Physiol. 230: 2019–2031, 2015. © 2015 Wiley Periodicals, Inc. PMID:25820299

  7. Native State Volume Fluctuations in Proteins as a Mechanism for Dynamic Allostery.

    PubMed

    Law, Anthony B; Sapienza, Paul J; Zhang, Jun; Zuo, Xiaobing; Petit, Chad M

    2017-03-15

    Allostery enables tight regulation of protein function in the cellular environment. Although existing models of allostery are firmly rooted in the current structure-function paradigm, the mechanistic basis for allostery in the absence of structural change remains unclear. In this study, we show that a typical globular protein is able to undergo significant changes in volume under native conditions while exhibiting no additional changes in protein structure. These native state volume fluctuations were found to correlate with changes in internal motions that were previously recognized as a source of allosteric entropy. This finding offers a novel mechanistic basis for allostery in the absence of canonical structural change. The unexpected observation that function can be derived from expanded, low density protein states has broad implications for our understanding of allostery and suggests that the general concept of the native state be expanded to allow for more variable physical dimensions with looser packing.

  8. Deconstructing autofluorescence: non-invasive detection and monitoring of biochemistry in cells and tissues (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Goldys, Ewa M.; Gosnell, Martin E.; Anwer, Ayad G.; Cassano, Juan C.; Sue, Carolyn M.; Mahbub, Saabah B.; Pernichery, Sandeep M.; Inglis, David W.; Adhikary, Partho P.; Jazayeri, Jalal A.; Cahill, Michael A.; Saad, Sonia; Pollock, Carol; Sutton-Mcdowall, Melanie L.; Thompson, Jeremy G.

    2016-03-01

    Automated and unbiased methods of non-invasive cell monitoring able to deal with complex biological heterogeneity are fundamentally important for biology and medicine. Label-free cell imaging provides information about endogenous fluorescent metabolites, enzymes and cofactors in cells. However extracting high content information from imaging of native fluorescence has been hitherto impossible. Here, we quantitatively characterise cell populations in different tissue types, live or fixed, by using novel image processing and a simple multispectral upgrade of a wide-field fluorescence microscope. Multispectral intrinsic fluorescence imaging was applied to patient olfactory neurosphere-derived cells, cell model of a human metabolic disease MELAS (mitochondrial myopathy, encephalomyopathy, lactic acidosis, stroke-like syndrome). By using an endogenous source of contrast, subtle metabolic variations have been detected between living cells in their full morphological context which made it possible to distinguish healthy from diseased cells before and after therapy. Cellular maps of native fluorophores, flavins, bound and free NADH and retinoids unveiled subtle metabolic signatures and helped uncover significant cell subpopulations, in particular a subpopulation with compromised mitochondrial function. The versatility of our method is further illustrated by detecting genetic mutations in cancer, non-invasive monitoring of CD90 expression, label-free tracking of stem cell differentiation, identifying stem cell subpopulations with varying functional characteristics, tissue diagnostics in diabetes, and assessing the condition of preimplantation embryos. Our optimal discrimination approach enables statistical hypothesis testing and intuitive visualisations where previously undetectable differences become clearly apparent.

  9. Heat Shock Protein 70 Family Members Interact with Crimean-Congo Hemorrhagic Fever Virus and Hazara Virus Nucleocapsid Proteins and Perform a Functional Role in the Nairovirus Replication Cycle.

    PubMed

    Surtees, Rebecca; Dowall, Stuart D; Shaw, Amelia; Armstrong, Stuart; Hewson, Roger; Carroll, Miles W; Mankouri, Jamel; Edwards, Thomas A; Hiscox, Julian A; Barr, John N

    2016-10-15

    The Nairovirus genus of the Bunyaviridae family contains serious human and animal pathogens classified within multiple serogroups and species. Of these serogroups, the Crimean-Congo hemorrhagic fever virus (CCHFV) serogroup comprises sole members CCHFV and Hazara virus (HAZV). CCHFV is an emerging zoonotic virus that causes often-fatal hemorrhagic fever in infected humans for which preventative or therapeutic strategies are not available. In contrast, HAZV is nonpathogenic to humans and thus represents an excellent model to study aspects of CCHFV biology under conditions of more-accessible biological containment. The three RNA segments that form the nairovirus genome are encapsidated by the viral nucleocapsid protein (N) to form ribonucleoprotein (RNP) complexes that are substrates for RNA synthesis and packaging into virus particles. We used quantitative proteomics to identify cellular interaction partners of CCHFV N and identified robust interactions with cellular chaperones. These interactions were validated using immunological methods, and the specific interaction between native CCHFV N and cellular chaperones of the HSP70 family was confirmed during live CCHFV infection. Using infectious HAZV, we showed for the first time that the nairovirus N-HSP70 association was maintained within both infected cells and virus particles, where N is assembled as RNPs. Reduction of active HSP70 levels in cells by the use of small-molecule inhibitors significantly reduced HAZV titers, and a model for chaperone function in the context of high genetic variability is proposed. These results suggest that chaperones of the HSP70 family are required for nairovirus replication and thus represent a genetically stable cellular therapeutic target for preventing nairovirus-mediated disease. Nairoviruses compose a group of human and animal viruses that are transmitted by ticks and associated with serious or fatal disease. One member is Crimean-Congo hemorrhagic fever virus (CCHFV), which is responsible for fatal human disease and is recognized as an emerging threat within Europe in response to climate change. No preventative or therapeutic strategies against nairovirus-mediated disease are currently available. Here we show that the N protein of CCHFV and the related Hazara virus interact with a cellular protein, HSP70, during both the intracellular and extracellular stages of the virus life cycle. The use of inhibitors that block HSP70 function reduces virus titers by up to 1,000-fold, suggesting that this interaction is important within the context of the nairovirus life cycle and may represent a potent target for antinairovirus therapies against which the virus cannot easily develop resistance. Copyright © 2016 Surtees et al.

  10. 3D Printing Variable Stiffness Foams Using Viscous Thread Instability

    PubMed Central

    Lipton, Jeffrey I.; Lipson, Hod

    2016-01-01

    Additive manufacturing of cellular structures has numerous applications ranging from fabrication of biological scaffolds and medical implants, to mechanical weight reduction and control over mechanical properties. Various additive manufacturing processes have been used to produce open regular cellular structures limited only by the resolution of the printer. These efforts have focused on printing explicitly designed cells or explicitly planning offsets between strands. Here we describe a technique for producing cellular structures implicitly by inducing viscous thread instability when extruding material. This process allows us to produce complex cellular structures at a scale that is finer than the native resolution of the printer. We demonstrate tunable effective elastic modulus and density that span two orders of magnitude. Fine grained cellular structures allow for fabrication of foams for use in a wide range of fields ranging from bioengineering, to robotics to food printing. PMID:27503148

  11. Complex, multi-scale small intestinal topography replicated in cellular growth substrates fabricated via chemical vapor deposition of Parylene C.

    PubMed

    Koppes, Abigail N; Kamath, Megha; Pfluger, Courtney A; Burkey, Daniel D; Dokmeci, Mehmet; Wang, Lin; Carrier, Rebecca L

    2016-08-22

    Native small intestine possesses distinct multi-scale structures (e.g., crypts, villi) not included in traditional 2D intestinal culture models for drug delivery and regenerative medicine. The known impact of structure on cell function motivates exploration of the influence of intestinal topography on the phenotype of cultured epithelial cells, but the irregular, macro- to submicron-scale features of native intestine are challenging to precisely replicate in cellular growth substrates. Herein, we utilized chemical vapor deposition of Parylene C on decellularized porcine small intestine to create polymeric intestinal replicas containing biomimetic irregular, multi-scale structures. These replicas were used as molds for polydimethylsiloxane (PDMS) growth substrates with macro to submicron intestinal topographical features. Resultant PDMS replicas exhibit multiscale resolution including macro- to micro-scale folds, crypt and villus structures, and submicron-scale features of the underlying basement membrane. After 10 d of human epithelial colorectal cell culture on PDMS substrates, the inclusion of biomimetic topographical features enhanced alkaline phosphatase expression 2.3-fold compared to flat controls, suggesting biomimetic topography is important in induced epithelial differentiation. This work presents a facile, inexpensive method for precisely replicating complex hierarchal features of native tissue, towards a new model for regenerative medicine and drug delivery for intestinal disorders and diseases.

  12. The Knowledge Base of Non-Native English-Speaking Teachers: Perspectives of Teachers and Administrators

    ERIC Educational Resources Information Center

    Zhang, Fengjuan; Zhan, Ju

    2014-01-01

    This study explores the knowledge base of non-native English-speaking teachers (NNESTs) working in the Canadian English as a second language (ESL) context. By examining NNESTs' experiences in seeking employment and teaching ESL in Canada, and investigating ESL program administrators' perceptions and hiring practices in relation to NNESTs, it…

  13. Multiword Lexical Units and Their Relationship to Impromptu Speech

    ERIC Educational Resources Information Center

    Hsu, Jeng-yih

    2007-01-01

    Public speaking can be very threatening to any native speakers of English, not to mention non-native EFL learners. Impromptu speech, perhaps the most challenging form of public speaking, is however being promoted in every city of the EFL countries. The case in Taiwan is no exceptional. Every year, dozens of impromptu speech contexts are held…

  14. Beneficial fungal interactions resulting in accelerated germination of Astragalus utahensis, a hard-seeded legume

    Treesearch

    Sean D. Eldredge

    2007-01-01

    Seed germination is pivotal in the life cycle of native plants in a restorative context because initiation of the metabolic processes critical to establishment is key to survival in such a competitive environment. Dormancy characteristics of some native plants including the subject species, Astragalus utahensis, have evolved mechanisms to control...

  15. D-Move: A Mobile Communication Based Delphi for Digital Natives to Support Embedded Research

    ERIC Educational Resources Information Center

    Petrovic, Otto

    2017-01-01

    Digital Natives are raised with computers and the Internet, which are a familiar part of their daily life. To gain insights into their attitude and behavior, methods and media for empirical research face new challenges like gamification, context oriented embedded research, integration of multiple data sources, and the increased importance of…

  16. Social and Emotional Distress among American Indian and Alaska Native Students: Research Findings. ERIC Digest.

    ERIC Educational Resources Information Center

    Clarke, Ardy SixKiller

    Many American Indian and Alaska Native (AI/AN) youth are repeatedly exposed to opportunities to participate in self-destructive and illegal behaviors. This digest examines risk factors associated with four contexts: peers, family, school, and community. Recent research has shown that, relative to national averages, AI/AN youth have higher rates of…

  17. American Indian and Alaska Native Children and Mental Health: Development, Context, Prevention, and Treatment. Child Psychology and Mental Health

    ERIC Educational Resources Information Center

    Sarche, Michelle C., Ed.; Spicer, Paul, Ed.; Farrell, Patricia, Ed.; Fitzgerald, Hiram E., Ed.

    2011-01-01

    This unique book examines the physical, psychological, social, and environmental factors that support or undermine healthy development in American Indian children, including economics, biology, and public policies. American Indian and Alaska Native youth suffer disproportionately higher rates of trauma, substance abuse, and youth suicide. At the…

  18. The Role of Native Language Instruction in Bilingual Education.

    ERIC Educational Resources Information Center

    Cardenas, Jose A.

    1984-01-01

    In the context of increasing criticism of bilingual education and the use of native language instruction, it must be remembered that they are based on a sound rationale. First, they address the need for continued learning as the child moves from one language to the other. Second, they address the need to diminish the alienation which children feel…

  19. Digital Natives, Digital Immigrants: An Analysis of Age and ICT Competency in Teacher Education

    ERIC Educational Resources Information Center

    Guo, Ruth Xiaoqing; Dobson, Teresa; Petrina, Stephen

    2008-01-01

    This article examines the intersection of age and ICT (information and communication technology) competency and critiques the "digital natives versus digital immigrants" argument proposed by Prensky (2001a, 2001b). Quantitative analysis was applied to a statistical data set collected in the context of a study with over 2,000 pre-service…

  20. "A'ole" Drugs! Cultural Practices and Drug Resistance of Rural Hawai'ian Youths

    ERIC Educational Resources Information Center

    Po'A-Kekuawela, Ka'Ohinani; Okamoto, Scott K.; Nebre, La Risa H.; Helm, Susana; Chin, Coralee I. H.

    2009-01-01

    This qualitative study examined how Native Hawai'ian youths from rural communities utilized cultural practices to promote drug resistance and/or abstinence. Forty-seven students from five different middle schools participated in gender-specific focus groups that focused on the cultural and environmental contexts of drug use for Native Hawai'ian…

  1. Home Environment and Self-Efficacy Beliefs among Native American, African American, and Latino Adolescents.

    PubMed

    Bradley, Robert H

    2018-05-07

    Context helps determine what individuals experience in the settings they inhabit. Context also helps determine the likelihood that those experiences will promote adaptive development. Theory suggests likely interplay between various aspects of home context and development of ideas about self that influence patterns of development for children. This study addressed relations between two aspects of home life (companionship and investment, modeling and encouragement) and three types of self-efficacy beliefs (enlisting social resources, independent learning, self-regulatory behavior) considered important for long-term adaptive functioning. The study focused on three groups of minority adolescents (Native American, African American, Latino). Relations were examined using regression models that also included four aspects of household risk that often hinder the development of self-efficacy. Although findings varied somewhat across the three groups, significant relations emerged between the two domains of home life examined and self-efficacy beliefs in all three groups, even controlling for overall household risk. Companionship and investment appeared particularly relevant for African American adolescents, while modeling and encouragement appeared particularly relevant for Native American adolescents. Both were relevant for Latino adolescents. © 2018 Family Process Institute.

  2. Stroop effects from newly learned color words: effects of memory consolidation and episodic context

    PubMed Central

    Geukes, Sebastian; Gaskell, M. Gareth; Zwitserlood, Pienie

    2015-01-01

    The Stroop task is an excellent tool to test whether reading a word automatically activates its associated meaning, and it has been widely used in mono- and bilingual contexts. Despite of its ubiquity, the task has not yet been employed to test the automaticity of recently established word-concept links in novel-word-learning studies, under strict experimental control of learning and testing conditions. In three experiments, we thus paired novel words with native language (German) color words via lexical association and subsequently tested these words in a manual version of the Stroop task. Two crucial findings emerged: When novel word Stroop trials appeared intermixed among native-word trials, the novel-word Stroop effect was observed immediately after the learning phase. If no native color words were present in a Stroop block, the novel-word Stroop effect only emerged 24 h later. These results suggest that the automatic availability of a novel word's meaning depends either on supportive context from the learning episode and/or on sufficient time for memory consolidation. We discuss how these results can be reconciled with the complementary learning systems account of word learning. PMID:25814973

  3. Three dimensional multi-cellular muscle-like tissue engineering in perfusion-based bioreactors.

    PubMed

    Cerino, Giulia; Gaudiello, Emanuele; Grussenmeyer, Thomas; Melly, Ludovic; Massai, Diana; Banfi, Andrea; Martin, Ivan; Eckstein, Friedrich; Grapow, Martin; Marsano, Anna

    2016-01-01

    Conventional tissue engineering strategies often rely on the use of a single progenitor cell source to engineer in vitro biological models; however, multi-cellular environments can better resemble the complexity of native tissues. Previous described co-culture models used skeletal myoblasts, as parenchymal cell source, and mesenchymal or endothelial cells, as stromal component. Here, we propose instead the use of adipose tissue-derived stromal vascular fraction cells, which include both mesenchymal and endothelial cells, to better resemble the native stroma. Percentage of serum supplementation is one of the crucial parameters to steer skeletal myoblasts toward either proliferation (20%) or differentiation (5%) in two-dimensional culture conditions. On the contrary, three-dimensional (3D) skeletal myoblast culture often simply adopts the serum content used in monolayer, without taking into account the new cell environment. When considering 3D cultures of mm-thick engineered tissues, homogeneous and sufficient oxygen supply is paramount to avoid formation of necrotic cores. Perfusion-based bioreactor culture can significantly improve the oxygen access to the cells, enhancing the viability and the contractility of the engineered tissues. In this study, we first investigated the influence of different serum supplementations on the skeletal myoblast ability to proliferate and differentiate during 3D perfusion-based culture. We tested percentages of serum promoting monolayer skeletal myoblast-proliferation (20%) and differentiation (5%) and suitable for stromal cell culture (10%) with a view to identify the most suitable condition for the subsequent co-culture. The 10% serum medium composition resulted in the highest number of mature myotubes and construct functionality. Co-culture with stromal vascular fraction cells at 10% serum also supported the skeletal myoblast differentiation and maturation, hence providing a functional engineered 3D muscle model that resembles the native multi-cellular environment. © 2015 Wiley Periodicals, Inc.

  4. Interaction of human low density lipoprotein and apolipoprotein B with ternary lipid microemulsion. Physical and functional properties.

    PubMed

    Chun, P W; Brumbaugh, E E; Shiremann, R B

    1986-12-31

    Based on data from sedimentation velocity experiments, electrophoresis, electron microscopy, cellular uptake studies, scanning molecular sieve chromatography using a quasi-three-dimensional data display and flow performance liquid chromatography (FPLC), models for the interaction of human serum low density lipoprotein (LDL) and of apolipoprotein B (apo B) with a ternary lipid microemulsion (ME) are proposed. The initial step in the interaction of LDL (Stokes radius 110 A) with the ternary microemulsion (Stokes radius 270 A) appears to be attachment of the LDL to emulsion particles. This attachment is followed by a very slow fusion into particles having a radius of approx. 280 A. Sonication of this mixture yields large aggregates. Electron micrographs of deoxycholate-solubilized apo B indicate an arrangement of apo B resembling strings of beads. During incubation, these particles also attach to the ternary microemulsion particles and, upon sonication, spherical particles result which resemble native LDL particles in size. Scanning chromatography corroborates the electron microscopy results. By appropriate choice of display angles in a quasi-three-dimensional display of the scanning data (corrected for gel apparent absorbance) taken at equal time intervals during passage of a sample through the column, changes in molecular radius of less than 10 A can be detected visually. Such a display gives a quantitative estimate of 101 +/- 2 A for these particles (compared to 110 A for native LDL). The LDL-ME particles and apo B-ME particles compete efficiently with native LDL for cellular binding and uptake. Cellular association studies indicate that both LDL- and apo B-ME particles are effective vehicles for lipid delivery into cells.

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

    FLANAGAN,J.M.; BEWLEY,M.C.

    It is generally accepted that the information necessary to specify the native, functional, three-dimensional structure of a protein is encoded entirely within its amino acid sequence; however, efficient reversible folding and unfolding is observed only with a subset of small single-domain proteins. Refolding experiments often lead to the formation of kinetically-trapped, misfolded species that aggregate, even in dilute solution. In the cellular environment, the barriers to efficient protein folding and maintenance of native structure are even larger due to the nature of this process. First, nascent polypeptides must fold in an extremely crowded environment where the concentration of macromolecules approachesmore » 300-400 mg/mL and on average, each ribosome is within its own diameter of another ribosome (1-3). These conditions of severe molecular crowding, coupled with high concentrations of nascent polypeptide chains, favor nonspecific aggregation over productive folding (3). Second, folding of newly-translated polypeptides occurs in the context of their vehtorial synthesis process. Amino acids are added to a growing nascent chain at the rate of -5 residues per set, which means that for a 300 residue protein its N-terminus will be exposed to the cytosol {approx}1 min before its C-terminus and be free to begin the folding process. However, because protein folding is highly cooperative, the nascent polypeptide cannot reach its native state until a complete folding domain (50-250 residues) has emerged from the ribosome. Thus, for a single-domain protein, the final steps in folding are only completed post-translationally since {approx}40 residues of a nascent chain are sequestered within the exit channel of the ribosome and are not available for folding (4). A direct consequence of this limitation in cellular folding is that during translation incomplete domains will exist in partially-folded states that tend to expose hydrophobic residues that are prone to aggregation and/or misfolding. Thus it is not surprising that, in cells, the protein folding process is error prone and organisms have evolved ''editing'' or quality control (QC) systems to assist in the folding, maintenance and, when necessary, selective removal of damaged proteins. In fact, there is growing evidence that failure of these QC-systems contributes to a number of disease states (5-8). This chapter describes our current understanding of the nature and mechanisms of the protein quality control systems in the cytosol of bacteria. Parallel systems are exploited in the cytosol and mitochondria of eukaryotes to prevent the accumulation of misfolded proteins.« less

  6. Bioluminescence resonance energy transfer (BRET) imaging of protein–protein interactions within deep tissues of living subjects

    PubMed Central

    Dragulescu-Andrasi, Anca; Chan, Carmel T.; Massoud, Tarik F.; Gambhir, Sanjiv S.

    2011-01-01

    Identifying protein–protein interactions (PPIs) is essential for understanding various disease mechanisms and developing new therapeutic approaches. Current methods for assaying cellular intermolecular interactions are mainly used for cells in culture and have limited use for the noninvasive assessment of small animal disease models. Here, we describe red light-emitting reporter systems based on bioluminescence resonance energy transfer (BRET) that allow for assaying PPIs both in cell culture and deep tissues of small animals. These BRET systems consist of the recently developed Renilla reniformis luciferase (RLuc) variants RLuc8 and RLuc8.6, used as BRET donors, combined with two red fluorescent proteins, TagRFP and TurboFP635, as BRET acceptors. In addition to the native coelenterazine luciferase substrate, we used the synthetic derivative coelenterazine-v, which further red-shifts the emission maxima of Renilla luciferases by 35 nm. We show the use of these BRET systems for ratiometric imaging of both cells in culture and deep-tissue small animal tumor models and validate their applicability for studying PPIs in mice in the context of rapamycin-induced FK506 binding protein 12 (FKBP12)-FKBP12 rapamycin binding domain (FRB) association. These red light-emitting BRET systems have great potential for investigating PPIs in the context of drug screening and target validation applications. PMID:21730157

  7. Measurement of Rapid Protein Diffusion in the Cytoplasm by Photo-Converted Intensity Profile Expansion.

    PubMed

    Gura Sadovsky, Rotem; Brielle, Shlomi; Kaganovich, Daniel; England, Jeremy L

    2017-03-14

    The fluorescence microscopy methods presently used to characterize protein motion in cells infer protein motion from indirect observables, rather than measuring protein motion directly. Operationalizing these methods requires expertise that can constitute a barrier to their broad utilization. Here, we have developed PIPE (photo-converted intensity profile expansion) to directly measure the motion of tagged proteins and quantify it using an effective diffusion coefficient. PIPE works by pulsing photo-convertible fluorescent proteins, generating a peaked fluorescence signal at the pulsed region, and analyzing the spatial expansion of the signal. We demonstrate PIPE's success in measuring accurate diffusion coefficients in silico and in vitro and compare effective diffusion coefficients of native cellular proteins and free fluorophores in vivo. We apply PIPE to measure diffusion anomality in the cell and use it to distinguish free fluorophores from native cellular proteins. PIPE's direct measurement and ease of use make it appealing for cell biologists. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. On the micro-indentation of plant cells in a tissue context

    NASA Astrophysics Data System (ADS)

    Mosca, Gabriella; Sapala, Aleksandra; Strauss, Soeren; Routier-Kierzkowska, Anne-Lise; Smith, Richard S.

    2017-02-01

    The effect of geometry on cell stiffness measured with micro-indentation techniques has been explored in single cells, however it is unclear if results on single cells can be readily transferred to indentation experiments performed on a tissue in vivo. Here we explored this question by using simulation models of osmotic treatments and micro-indentation experiments on 3D multicellular tissues with the finite element method. We found that the cellular context does affect measured cell stiffness, and that several cells of context in each direction are required for optimal results. We applied the model to micro-indentation data obtained with cellular force microscopy on the sepal of A. thaliana, and found that differences in measured stiffness could be explained by cellular geometry, and do not necessarily indicate differences in cell wall material properties or turgor pressure.

  9. Learner Agency and Non-Native Speaker Identity in Pedagogical Lingua Franca Conversations: Insights from Intercultural Telecollaboration in Foreign Language Education

    ERIC Educational Resources Information Center

    Kohn, Kurt; Hoffstaedter, Petra

    2017-01-01

    This article discusses insights gained from a case study on telecollaboration for intercultural communication in foreign language school contexts. Focus was on non-native English and German lingua franca conversations between pairs of students (aged 14-16, B1 level) from schools in France, Germany, the Netherlands and Spain. Telecollaboration…

  10. Components and Context: Exploring Sources of Reading Difficulties for Language Minority Learners and Native English Speakers in Urban Schools

    ERIC Educational Resources Information Center

    Kieffer, Michael J.; Vukovic, Rose K.

    2012-01-01

    Drawing on the cognitive and ecological domains within the componential model of reading, this longitudinal study explores heterogeneity in the sources of reading difficulties for language minority learners and native English speakers in urban schools. Students (N = 150) were followed from first through third grade and assessed annually on…

  11. The Catholic School Advantage and Common School Effect Examined: A Comparison between Muslim Immigrant and Native Pupils in Flanders

    ERIC Educational Resources Information Center

    Agirdag, Orhan; Driessen, Geert; Merry, Michael S.

    2017-01-01

    This study investigates the impact of Catholic schooling on academic achievement of native Belgian and Muslim immigrant pupils. The distinctive characteristics of Catholic schools in Belgium (Flanders) form an exceptionally suitable context to study this. Multilevel latent growth curve analyses are conducted with data from approximately 5,000…

  12. With All My Relations: Counseling American Indians and Alaska Natives within a Familial Context

    ERIC Educational Resources Information Center

    Harper, Faith G.

    2011-01-01

    Statistics show that two thirds of American Indians and Alaska Natives (AIs/ANs) live outside of tribal areas, and 50% of those individuals who seek counseling services will not use tribal resources. There is a strong likelihood that counselors will have the opportunity to provide services to AI/AN clients. The review of the academic literature…

  13. Influence of Child Behavioral Problems and Parenting Stress on Parent-Child Conflict among Low-Income Families: The Moderating Role of Maternal Nativity

    ERIC Educational Resources Information Center

    Garcia, Aileen S.; Ren, Lixin; Esteraich, Jan M.; Raikes, Helen H.

    2017-01-01

    This study was designed to examine whether parenting stress and child behavioral problems are significant predictors of parent-child conflict in the context of low-income families and how these relations are moderated by maternal nativity. The authors conducted multiple regression analyses to examine relations between teachers' report of…

  14. Critically Evaluating Prensky in a Language Learning Context: The "Digital Natives/Immigrants Debate" and Its Implications for CALL

    ERIC Educational Resources Information Center

    Benini, Silvia; Murray, Liam

    2013-01-01

    More than 10 years have passed since the first introduction of the term "digital natives" in Prensky's (2001a, 2001b) two seminal articles. Prensky argues that students today, having grown up in the Digital Age, learn differently from their predecessors, or "digital immigrants". As such, the pedagogical tools and methods used…

  15. Aquatic species invasions in the context of fire and climate change

    Treesearch

    Michael K. Young

    2012-01-01

    This paper focuses on the nexus among native and nonnative fishes with respect to fire and climate change in the western United States. Although many taxa are involved, I emphasize native and nonnative salmonids because these are obligate coldwater species that might be expected to respond strongly to fire and because most research has been conducted on these fishes....

  16. Native American Perspectives on Educational Experiences from within the Not So Ivory Tower

    ERIC Educational Resources Information Center

    Holmes, Frances Kay

    2013-01-01

    This dissertation explores how education has had an impact on the lives of twenty-three professors who are Native. Within the context of this study, education may refer to either learning in the western frame of schooling or non western forms of Indigenous education. While many individuals would define education as a process that develops life and…

  17. Inclusive Education: An Examination of School Relationships and Student Interactions

    ERIC Educational Resources Information Center

    Sanchez-Marti, Angelina; Ramirez-Iniguez, Alma A.

    2012-01-01

    The aim of this paper is to examine inclusive education in multicultural contexts from an interaction networks perspective. The paper is based on the idea that inclusive education can be better understood by studying how native and non-native students interact, and what kinds of networks they establish in school. To do so, we assume two premises:…

  18. The Sensorless Pore Module of Voltage-gated K+ Channel Family 7 Embodies the Target Site for the Anticonvulsant Retigabine.

    PubMed

    Syeda, Ruhma; Santos, Jose S; Montal, Mauricio

    2016-02-05

    KCNQ (voltage-gated K(+) channel family 7 (Kv7)) channels control cellular excitability and underlie the K(+) current sensitive to muscarinic receptor signaling (the M current) in sympathetic neurons. Here we show that the novel anti-epileptic drug retigabine (RTG) modulates channel function of pore-only modules (PMs) of the human Kv7.2 and Kv7.3 homomeric channels and of Kv7.2/3 heteromeric channels by prolonging the residence time in the open state. In addition, the Kv7 channel PMs are shown to recapitulate the single-channel permeation and pharmacological specificity characteristics of the corresponding full-length proteins in their native cellular context. A mutation (W265L) in the reconstituted Kv7.3 PM renders the channel insensitive to RTG and favors the conductive conformation of the PM, in agreement to what is observed when the Kv7.3 mutant is heterologously expressed. On the basis of the new findings and homology models of the closed and open conformations of the Kv7.3 PM, we propose a structural mechanism for the gating of the Kv7.3 PM and for the site of action of RTG as a Kv7.2/Kv7.3 K(+) current activator. The results validate the modular design of human Kv channels and highlight the PM as a high-fidelity target for drug screening of Kv channels. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. The Sensorless Pore Module of Voltage-gated K+ Channel Family 7 Embodies the Target Site for the Anticonvulsant Retigabine*

    PubMed Central

    Syeda, Ruhma; Santos, Jose S.; Montal, Mauricio

    2016-01-01

    KCNQ (voltage-gated K+ channel family 7 (Kv7)) channels control cellular excitability and underlie the K+ current sensitive to muscarinic receptor signaling (the M current) in sympathetic neurons. Here we show that the novel anti-epileptic drug retigabine (RTG) modulates channel function of pore-only modules (PMs) of the human Kv7.2 and Kv7.3 homomeric channels and of Kv7.2/3 heteromeric channels by prolonging the residence time in the open state. In addition, the Kv7 channel PMs are shown to recapitulate the single-channel permeation and pharmacological specificity characteristics of the corresponding full-length proteins in their native cellular context. A mutation (W265L) in the reconstituted Kv7.3 PM renders the channel insensitive to RTG and favors the conductive conformation of the PM, in agreement to what is observed when the Kv7.3 mutant is heterologously expressed. On the basis of the new findings and homology models of the closed and open conformations of the Kv7.3 PM, we propose a structural mechanism for the gating of the Kv7.3 PM and for the site of action of RTG as a Kv7.2/Kv7.3 K+ current activator. The results validate the modular design of human Kv channels and highlight the PM as a high-fidelity target for drug screening of Kv channels. PMID:26627826

  20. Informal Language Learning Setting: Technology or Social Interaction?

    ERIC Educational Resources Information Center

    Bahrani, Taher; Sim, Tam Shu

    2012-01-01

    Based on the informal language learning theory, language learning can occur outside the classroom setting unconsciously and incidentally through interaction with the native speakers or exposure to authentic language input through technology. However, an EFL context lacks the social interaction which naturally occurs in an ESL context. To explore…

  1. Invasive plants may promote predator-mediated feedback that inhibits further invasion

    PubMed Central

    Smith, Lauren M; Schmitz, Oswald J

    2015-01-01

    Understanding the impacts of invasive species requires placing invasion within a full community context. Plant invaders are often considered in the context of herbivores that may drive invasion by avoiding invaders while consuming natives (enemy escape), or inhibit invasion by consuming invaders (biotic resistance). However, predators that attack those herbivores are rarely considered as major players in invasion. Invasive plants often promote predators, generally by providing improved habitat. Here, we show that predator-promoting invaders may initiate a negative feedback loop that inhibits invasion. By enabling top-down control of herbivores, predator-promoting invaders lose any advantage gained through enemy escape, indirectly favoring natives. In cases where palatable invaders encounter biotic resistance, predator promotion may allow an invader to persist, but not dominate. Overall, results indicate that placing invaders in a full community context may reveal reduced impacts of invaders compared to expectations based on simple plant–plant or plant–herbivore subsystems. PMID:26120430

  2. Native state volume fluctuations in proteins as a mechanism for dynamic allostery

    DOE PAGES

    Law, Anthony B.; Sapienza, Paul J.; Zhang, Jun; ...

    2017-01-17

    Allostery enables tight regulation of protein function in the cellular environment. While existing models of allostery are firmly rooted in the current structure-function paradigm, the mechanistic basis for allostery in the absence of structural change remains unclear. In this study, we show that a typical globular protein is able to undergo significant changes in volume under native conditions while exhibiting no additional changes in protein structure. These native state volume fluctuations were found to correlate with changes in internal motions that were previously recognized as a source of allosteric entropy. This finding offers a novel mechanistic basis for allostery inmore » the absence of canonical structural change. As a result, the unexpected observation that function can be derived from expanded, low density protein states has broad implications for our understanding of allostery and suggests that the general concept of the native state be expanded to allow for more variable physical dimensions with looser packing.« less

  3. Passport, a native Tc1 transposon from flatfish, is functionally active in vertebrate cells

    PubMed Central

    Clark, Karl J.; Carlson, Daniel F.; Leaver, Michael J.; Foster, Linda K.; Fahrenkrug, Scott C.

    2009-01-01

    The Tc1/mariner family of DNA transposons is widespread across fungal, plant and animal kingdoms, and thought to contribute to the evolution of their host genomes. To date, an active Tc1 transposon has not been identified within the native genome of a vertebrate. We demonstrate that Passport, a native transposon isolated from a fish (Pleuronectes platessa), is active in a variety of vertebrate cells. In transposition assays, we found that the Passport transposon system improved stable cellular transgenesis by 40-fold, has an apparent preference for insertion into genes, and is subject to overproduction inhibition like other Tc1 elements. Passport represents the first vertebrate Tc1 element described as both natively intact and functionally active, and given its restricted phylogenetic distribution, may be contemporaneously active. The Passport transposon system thus complements the available genetic tools for the manipulation of vertebrate genomes, and may provide a unique system for studying the infiltration of vertebrate genomes by Tc1 elements. PMID:19136468

  4. Passport, a native Tc1 transposon from flatfish, is functionally active in vertebrate cells.

    PubMed

    Clark, Karl J; Carlson, Daniel F; Leaver, Michael J; Foster, Linda K; Fahrenkrug, Scott C

    2009-03-01

    The Tc1/mariner family of DNA transposons is widespread across fungal, plant and animal kingdoms, and thought to contribute to the evolution of their host genomes. To date, an active Tc1 transposon has not been identified within the native genome of a vertebrate. We demonstrate that Passport, a native transposon isolated from a fish (Pleuronectes platessa), is active in a variety of vertebrate cells. In transposition assays, we found that the Passport transposon system improved stable cellular transgenesis by 40-fold, has an apparent preference for insertion into genes, and is subject to overproduction inhibition like other Tc1 elements. Passport represents the first vertebrate Tc1 element described as both natively intact and functionally active, and given its restricted phylogenetic distribution, may be contemporaneously active. The Passport transposon system thus complements the available genetic tools for the manipulation of vertebrate genomes, and may provide a unique system for studying the infiltration of vertebrate genomes by Tc1 elements.

  5. Liquid scanning transmission electron microscopy: imaging protein complexes in their native environment in whole eukaryotic cells.

    PubMed

    Peckys, Diana B; de Jonge, Niels

    2014-04-01

    Scanning transmission electron microscopy (STEM) of specimens in liquid, so-called Liquid STEM, is capable of imaging the individual subunits of macromolecular complexes in whole eukaryotic cells in liquid. This paper discusses this new microscopy modality within the context of state-of-the-art microscopy of cells. The principle of operation and equations for the resolution are described. The obtained images are different from those acquired with standard transmission electron microscopy showing the cellular ultrastructure. Instead, contrast is obtained on specific labels. Images can be recorded in two ways, either via STEM at 200 keV electron beam energy using a microfluidic chamber enclosing the cells, or via environmental scanning electron microscopy at 30 keV of cells in a wet environment. The first series of experiments involved the epidermal growth factor receptor labeled with gold nanoparticles. The labels were imaged in whole fixed cells with nanometer resolution. Since the cells can be kept alive in the microfluidic chamber, it is also feasible to detect the labels in unfixed, live cells. The rapid sample preparation and imaging allows studies of multiple whole cells.

  6. Components and context: exploring sources of reading difficulties for language minority learners and native English speakers in urban schools.

    PubMed

    Kieffer, Michael J; Vukovic, Rose K

    2012-01-01

    Drawing on the cognitive and ecological domains within the componential model of reading, this longitudinal study explores heterogeneity in the sources of reading difficulties for language minority learners and native English speakers in urban schools. Students (N = 150) were followed from first through third grade and assessed annually on standardized English language and reading measures. Structural equation modeling was used to investigate the relative contributions of code-related and linguistic comprehension skills in first and second grade to third grade reading comprehension. Linguistic comprehension and the interaction between linguistic comprehension and code-related skills each explained substantial variation in reading comprehension. Among students with low reading comprehension, more than 80% demonstrated weaknesses in linguistic comprehension alone, whereas approximately 15% demonstrated weaknesses in both linguistic comprehension and code-related skills. Results were remarkably similar for the language minority learners and native English speakers, suggesting the importance of their shared socioeconomic backgrounds and schooling contexts.

  7. Opening up to Native Speaker Norms: The Use of /?/ in the Speech of Canadian French Immersion Students

    ERIC Educational Resources Information Center

    Nadasdi, Terry; Vickerman, Alison

    2017-01-01

    Our study examines the extent to which French immersion students use lax /?/ in the same linguistic context as native speakers of Canadian French. Our results show that the lax variant is vanishingly rare in the speech of immersion students and is used by only a small minority of individuals. This is interpreted as a limitation of French immersion…

  8. Pragmatic Competence and Social Power Awareness: The Case of Written and Spoken Discourse in Non-Native English Environments

    ERIC Educational Resources Information Center

    Pérez-Sabater, Carmen; Montero-Fleta, Begoña

    2014-01-01

    Following one of the new challenges suggested by the Common European Framework of Reference for Languages, a treatment was developed to enhance pragmatic competence, since this competence is not easy to acquire by non-native speakers. Within this context, we focused on pragmatic awareness in the workplace, an area of expertise in growing demand…

  9. Range-wide conservation of Pinus aristata: A genetic collection with ecological context for proactive management today and resources for tomorrow

    Treesearch

    Anna W. Schoettle; Jonathan C. Coop

    2017-01-01

    Tree species are highly vulnerable to anthropogenic environmental change, and are increasingly being challenged by non-native pests and climate change. Rocky Mountain bristlecone pines are long-lived, exhibit delayed maturation, have low genetic diversity, and inhabit cold, high-elevation environments. They are threatened by the non-native disease white pine blister...

  10. Applications of systems biology towards microbial fuel production.

    PubMed

    Gowen, Christopher M; Fong, Stephen S

    2011-10-01

    Harnessing the immense natural diversity of biological functions for economical production of fuel has enormous potential benefits. Inevitably, however, the native capabilities for any given organism must be modified to increase the productivity or efficiency of a biofuel bioprocess. From a broad perspective, the challenge is to sufficiently understand the details of cellular functionality to be able to prospectively predict and modify the cellular function of a microorganism. Recent advances in experimental and computational systems biology approaches can be used to better understand cellular level function and guide future experiments. With pressure to quickly develop viable, renewable biofuel processes a balance must be maintained between obtaining depth of biological knowledge and applying that knowledge. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Acoustic variability within and across German, French, and American English vowels: phonetic context effects.

    PubMed

    Strange, Winifred; Weber, Andrea; Levy, Erika S; Shafiro, Valeriy; Hisagi, Miwako; Nishi, Kanae

    2007-08-01

    Cross-language perception studies report influences of speech style and consonantal context on perceived similarity and discrimination of non-native vowels by inexperienced and experienced listeners. Detailed acoustic comparisons of distributions of vowels produced by native speakers of North German (NG), Parisian French (PF) and New York English (AE) in citation (di)syllables and in sentences (surrounded by labial and alveolar stops) are reported here. Results of within- and cross-language discriminant analyses reveal striking dissimilarities across languages in the spectral/temporal variation of coarticulated vowels. As expected, vocalic duration was most important in differentiating NG vowels; it did not contribute to PF vowel classification. Spectrally, NG long vowels showed little coarticulatory change, but back/low short vowels were fronted/raised in alveolar context. PF vowels showed greater coarticulatory effects overall; back and front rounded vowels were fronted, low and mid-low vowels were raised in both sentence contexts. AE mid to high back vowels were extremely fronted in alveolar contexts, with little change in mid-low and low long vowels. Cross-language discriminant analyses revealed varying patterns of spectral (dis)similarity across speech styles and consonantal contexts that could, in part, account for AE listeners' perception of German and French front rounded vowels, and "similar" mid-high to mid-low vowels.

  12. Reduction in fecundity and shifts in cellular processes by a native virus on an invasive insect

    USDA-ARS?s Scientific Manuscript database

    Pathogens and their vectors have co-evolutionary histories that are intricately intertwined with their ecologies, environments and genetic interactions. The majority of non-persistently transmitted plant viruses are transmitted by aphid species. One important aphid vector in soybean-growing regions ...

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

    Kleiner, J.B.; Amiel, D.; Harwood, F.L.

    A rabbit model for anterior cruciate ligament (ACL) reconstruction using autogenous patellar tendon was utilized to study the early events of autograft cellular dynamics. Biochemical, autoradiographic, histological, and vascular injection techniques demonstrated that the native autograft cell population rapidly necroses. This repopulation occurs without a vascular contribution; cells entering the autograft are reliant upon synovial fluid nutrition.

  14. Pepsinized cashew proteins are hypoallergenic and immunogenic and provide effective immunotherapy in mice with cashew allergy.

    PubMed

    Kulis, Mike; Macqueen, Ian; Li, Yifan; Guo, Rishu; Zhong, Xiao-Ping; Burks, A Wesley

    2012-09-01

    IgE-mediated allergic reactions to cashews and other nuts can trigger life-threatening anaphylaxis. Proactive therapies to decrease reaction severity do not exist. We aimed to determine the efficacy of pepsin-digested cashew proteins used as immunotherapy in a murine model of cashew allergy. Mice were sensitized to cashew and then underwent challenges with digested or native cashew allergens to assess the allergenicity of the protein preparations. Using native or pepsinized cashew proteins, mice underwent oral or intraperitoneal sensitization protocols to determine the immunogenic properties of the protein preparations. Finally, cashew-sensitized mice underwent an immunotherapy protocol with native or pepsinized cashew proteins and subsequent provocation challenges. Pepsinized cashew proteins elicited weaker allergic reactions than native cashew proteins but importantly retained the ability to stimulate cellular proliferation and cytokine production. Mice sensitized with pepsinized proteins reacted on challenge with native allergens, demonstrating that pepsinized allergens retain immunogenicity in vivo. Immunotherapy with pepsinized cashew allergens significantly decreased allergic symptoms and body temperature decrease relative to placebo after challenge with native and pepsinized proteins. Immunologic changes were comparable after immunotherapy with native or pepsinized allergens: T(H)2-type cytokine secretion from splenocytes was decreased, whereas specific IgG(1) and IgG(2a) levels were increased. Pepsinized cashew proteins are effective in treating cashew allergy in mice and appear to work through the same mechanisms as native protein immunotherapy. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  15. The role thermal physiology plays in species invasion

    PubMed Central

    Kelley, Amanda L.

    2014-01-01

    The characterization of physiological phenotypes that may play a part in the establishment of non-native species can broaden our understanding about the ecology of species invasion. Here, an assessment was carried out by comparing the responses of invasive and native species to thermal stress. The goal was to identify physiological patterns that facilitate invasion success and to investigate whether these traits are widespread among invasive ectotherms. Four hypotheses were generated and tested using a review of the literature to determine whether they could be supported across taxonomically diverse invasive organisms. The four hypotheses are as follows: (i) broad geographical temperature tolerances (thermal width) confer a higher upper thermal tolerance threshold for invasive rather than native species; (ii) the upper thermal extreme experienced in nature is more highly correlated with upper thermal tolerance threshold for invasive vs. native animals; (iii) protein chaperone expression—a cellular mechanism that underlies an organism's thermal tolerance threshold—is greater in invasive organisms than in native ones; and (iv) acclimation to higher temperatures can promote a greater range of thermal tolerance for invasive compared with native species. Each hypothesis was supported by a meta-analysis of the invasive/thermal physiology literature, providing further evidence that physiology plays a substantial role in the establishment of invasive ectotherms. PMID:27293666

  16. CN-GELFrEE - Clear Native Gel-eluted Liquid Fraction Entrapment Electrophoresis

    PubMed Central

    Skinner, Owen S.; Do Vale, Luis H. F.; Catherman, Adam D.; Havugimana, Pierre C.; Valle de Sousa, Marcelo; Domont, Gilberto B.; Kelleher, Neil L.; Compton, Philip D.

    2016-01-01

    Protein complexes perform an array of crucial cellular functions. Elucidating their non-covalent interactions and dynamics is paramount for understanding the role of complexes in biological systems. While the direct characterization of biomolecular assemblies has become increasingly important in recent years, native fractionation techniques that are compatible with downstream analysis techniques, including mass spectrometry, are necessary to further expand these studies. Nevertheless, the field lacks a high-throughput, wide-range, high-recovery separation method for native protein assemblies. Here, we present clear native gel-eluted liquid fraction entrapment electrophoresis (CN-GELFrEE), which is a novel separation modality for non-covalent protein assemblies. CN-GELFrEE separation performance was demonstrated by fractionating complexes extracted from mouse heart. Fractions were collected over 2 hr and displayed discrete bands ranging from ~30 to 500 kDa. A consistent pattern of increasing molecular weight bandwidths was observed, each ranging ~100 kDa. Further, subsequent reanalysis of native fractions via SDS-PAGE showed molecular-weight shifts consistent with the denaturation of protein complexes. Therefore, CN-GELFrEE was proved to offer the ability to perform high-resolution and high-recovery native separations on protein complexes from a large molecular weight range, providing fractions that are compatible with downstream protein analyses. PMID:26967310

  17. Smooth muscle cell seeding of decellularized scaffolds: the importance of bioreactor preconditioning to development of a more native architecture for tissue-engineered blood vessels.

    PubMed

    Yazdani, Saami K; Watts, Benjamin; Machingal, Masood; Jarajapu, Yagna P R; Van Dyke, Mark E; Christ, George J

    2009-04-01

    Vascular smooth muscle cells (VSMCs) impart important functional characteristics in the native artery and, therefore, should logically be incorporated in the development of tissue-engineered blood vessels. However, the native architecture and low porosity of naturally derived biomaterials (i.e., decellularized vessels) have impeded efforts to seed and incorporate a VSMC layer in tissue-engineered blood vessels. To this end, the goal of this study was to develop improved methods for seeding, proliferation, and maturation of VSMCs on decellularized porcine carotid arteries. Decellularized vessels were prepared in the absence and presence of the adventitial layer, and statically seeded with a pipette containing a suspension of rat aortic VSMCs. After cell seeding, recellularized engineered vessels were placed in a custom bioreactor system for 1-2 weeks to enhance cellular proliferation, alignment, and maturation. Initial attachment of VSMCs was dramatically enhanced by removing the adventitial layer of the decellularized porcine artery. Moreover, cyclic bioreactor conditioning (i.e., flow and pressure) resulted in increased VSMC proliferation and accelerated formation of a muscularized medial layer in the absence of the adventitial layer during the first week of preconditioning. Fura-2-based digital imaging microscopy revealed marked and reproducible depolarization-induced calcium mobilization after bioreactor preconditioning in the absence, but not in the presence, of the adventitia. The major finding of this investigation is that bioreactor preconditioning accelerates the formation of a significant muscular layer on decellularized scaffolds, in particular on adventitia-denuded scaffolds. Further, the VSMC layer of bioreactor-preconditioned vessels was capable of mobilizing calcium in response to cellular depolarization. These findings represent an important first step toward the development of tissue-engineered vascular grafts that more closely mimic native vasculature.

  18. Cellular therapy in bone-tendon interface regeneration

    PubMed Central

    Rothrauff, Benjamin B; Tuan, Rocky S

    2014-01-01

    The intrasynovial bone-tendon interface is a gradual transition from soft tissue to bone, with two intervening zones of uncalcified and calcified fibrocartilage. Following injury, the native anatomy is not restored, resulting in inferior mechanical properties and an increased risk of re-injury. Recent in vivo studies provide evidence of improved healing when surgical repair of the bone-tendon interface is augmented with cells capable of undergoing chondrogenesis. In particular, cellular therapy in bone-tendon healing can promote fibrocartilage formation and associated improvements in mechanical properties. Despite these promising results in animal models, cellular therapy in human patients remains largely unexplored. This review highlights the development and structure-function relationship of normal bone-tendon insertions. The natural healing response to injury is discussed, with subsequent review of recent research on cellular approaches for improved healing. Finally, opportunities for translating in vivo findings into clinical practice are identified. PMID:24326955

  19. International Students' Emotional Security and Dignity in an Australian Context: An Aspect of Psychological Well-Being

    ERIC Educational Resources Information Center

    Tananuraksakul, Noparat; Hall, David

    2011-01-01

    This article explores non-native English-speaking students' emotional security and dignity responses to their English language proficiency in an Australian context. Confidence is a source of emotional security bolstering dignity. Without it, students lack emotional security, diminishing their dignity when communicating with culturally different…

  20. Literacy achievement of children with intellectual disabilities and differing linguistic backgrounds.

    PubMed

    Verhoeven, L; Vermeer, A

    2006-10-01

    The aim of the present study was to examine the literacy achievement of 10- to 12-year-old native and non-native children with intellectual disabilities (ID) living in the Netherlands. An intriguing question within this context was whether the second language learning non-native children with ID would show a double disadvantage when compared with their monolingual Dutch peers with no ID. Dutch literacy scores in the domains of word decoding, vocabulary, syntax and text were therefore compared for: (1) intellectually disabled native Dutch children; (2) intellectually disabled non-native children; (3) normally developing native Dutch children; and (4) normally developing non-native children. The interrelations between literacy subskills were also compared for native vs. non-native children with ID. The native and non-native students diagnosed as intellectually disabled produced substantially lower literacy scores than their non-disabled peers. The differences between the native (L1) and non-native (L2) children in regular vs. special education were found to depend on the aspect of literacy considered. Word decoding and language skills turned out to significantly predict the children's reading comprehension, although some differences in the strength of relationships could also be evidenced. The literacy achievement of intellectually disabled children with differing linguistic backgrounds generally falls behind that of their non-disabled peers. For word decoding, the non-native children in regular and special education were generally able to keep up with their native peers. For higher-order literacy abilities closely related to the mental lexicon, sentence processing and text processing, however, significant differences in the performances of the native (L1) and non-native (L2) children in regular vs. special education were found, suggesting a double disadvantage for the non-native children in special education.

  1. Combining Physicochemical and Evolutionary Information for Protein Contact Prediction

    PubMed Central

    Schneider, Michael; Brock, Oliver

    2014-01-01

    We introduce a novel contact prediction method that achieves high prediction accuracy by combining evolutionary and physicochemical information about native contacts. We obtain evolutionary information from multiple-sequence alignments and physicochemical information from predicted ab initio protein structures. These structures represent low-energy states in an energy landscape and thus capture the physicochemical information encoded in the energy function. Such low-energy structures are likely to contain native contacts, even if their overall fold is not native. To differentiate native from non-native contacts in those structures, we develop a graph-based representation of the structural context of contacts. We then use this representation to train an support vector machine classifier to identify most likely native contacts in otherwise non-native structures. The resulting contact predictions are highly accurate. As a result of combining two sources of information—evolutionary and physicochemical—we maintain prediction accuracy even when only few sequence homologs are present. We show that the predicted contacts help to improve ab initio structure prediction. A web service is available at http://compbio.robotics.tu-berlin.de/epc-map/. PMID:25338092

  2. English or Englishes? Outer and Expanding Circle Teachers' Awareness of and Attitudes towards Their Own Variants of English in ESL/EFL Teaching Contexts

    ERIC Educational Resources Information Center

    Monfared, Abbas; Khatib, Mohammad

    2018-01-01

    One of the challenging issues that has gained much attention, and has in fact sparked much debate, within the emergence and acquisition of World Englishes, is the Native- Non-native accent, especially its relationship with teachers' and learners' identity and selection of an appropriate pedagogic model. This paper investigates the attitudes of 260…

  3. Health Promotion and Substance Abuse Prevention among American Indian and Alaska Native Communities: Issues in Cultural Competence. Cultural Competence Series 9. Special Collaborative Edition.

    ERIC Educational Resources Information Center

    Trimble, Joseph E., Ed.; Beauvais, Fred, Ed.

    Substance abuse continues to be one of the most damaging and chronic health problems faced by Indian people. American Indian and Alaska Native (AI/AN) substance abuse prevention and treatment programs must be framed within the broader context of the widening health disparities between AI/AN communities and the general population. Successful…

  4. Cultural context in the effort to improve oral health among Alaska Native people: the dental health aide therapist model.

    PubMed

    Wetterhall, Scott; Burrus, Barri; Shugars, Daniel; Bader, James

    2011-10-01

    The Alaska Native people in rural Alaska face serious challenges in obtaining dental care. Itinerant care models have failed to meet their needs for more than 50 years. The dental health aide therapist (DHAT) model, which entails training midlevel care providers to perform limited restorative, surgical, and preventive procedures, was adopted to address some of the limitations of the itinerant model. We used quantitative and qualitative methods to assess residents' satisfaction with the model and the role of DHATs in the cultural context in which they operate. Our findings suggest that the DHAT model can provide much-needed access to urgent care and is beneficial from a comprehensive cultural perspective.

  5. Quantifying the intelligibility of speech in noise for non-native listeners.

    PubMed

    van Wijngaarden, Sander J; Steeneken, Herman J M; Houtgast, Tammo

    2002-04-01

    When listening to languages learned at a later age, speech intelligibility is generally lower than when listening to one's native language. The main purpose of this study is to quantify speech intelligibility in noise for specific populations of non-native listeners, only broadly addressing the underlying perceptual and linguistic processing. An easy method is sought to extend these quantitative findings to other listener populations. Dutch subjects listening to Germans and English speech, ranging from reasonable to excellent proficiency in these languages, were found to require a 1-7 dB better speech-to-noise ratio to obtain 50% sentence intelligibility than native listeners. Also, the psychometric function for sentence recognition in noise was found to be shallower for non-native than for native listeners (worst-case slope around the 50% point of 7.5%/dB, compared to 12.6%/dB for native listeners). Differences between native and non-native speech intelligibility are largely predicted by linguistic entropy estimates as derived from a letter guessing task. Less effective use of context effects (especially semantic redundancy) explains the reduced speech intelligibility for non-native listeners. While measuring speech intelligibility for many different populations of listeners (languages, linguistic experience) may be prohibitively time consuming, obtaining predictions of non-native intelligibility from linguistic entropy may help to extend the results of this study to other listener populations.

  6. Quantifying the intelligibility of speech in noise for non-native listeners

    NASA Astrophysics Data System (ADS)

    van Wijngaarden, Sander J.; Steeneken, Herman J. M.; Houtgast, Tammo

    2002-04-01

    When listening to languages learned at a later age, speech intelligibility is generally lower than when listening to one's native language. The main purpose of this study is to quantify speech intelligibility in noise for specific populations of non-native listeners, only broadly addressing the underlying perceptual and linguistic processing. An easy method is sought to extend these quantitative findings to other listener populations. Dutch subjects listening to Germans and English speech, ranging from reasonable to excellent proficiency in these languages, were found to require a 1-7 dB better speech-to-noise ratio to obtain 50% sentence intelligibility than native listeners. Also, the psychometric function for sentence recognition in noise was found to be shallower for non-native than for native listeners (worst-case slope around the 50% point of 7.5%/dB, compared to 12.6%/dB for native listeners). Differences between native and non-native speech intelligibility are largely predicted by linguistic entropy estimates as derived from a letter guessing task. Less effective use of context effects (especially semantic redundancy) explains the reduced speech intelligibility for non-native listeners. While measuring speech intelligibility for many different populations of listeners (languages, linguistic experience) may be prohibitively time consuming, obtaining predictions of non-native intelligibility from linguistic entropy may help to extend the results of this study to other listener populations.

  7. Why do people use exotic plants in their local medical systems? A systematic review based on Brazilian local communities.

    PubMed

    Medeiros, Patrícia Muniz de; Ferreira Júnior, Washington Soares; Ramos, Marcelo Alves; Silva, Taline Cristina da; Ladio, Ana Haydée; Albuquerque, Ulysses Paulino

    2017-01-01

    Efforts have been made to understand the processes that lead to the introduction of exotic species into local pharmacopoeias. Among those efforts, the diversification hypothesis predicts that exotic plants are introduced in local medical systems to amplify the repertoire of knowledge related to the treatment of diseases, filling blanks that were not occupied by native species. Based on such hypothesis, this study aimed to contribute to this discussion using the context of local Brazilian populations. We performed a systematic review of Brazilian studies up to 2011 involving medicinal plants, excluding those studies that presented a high risk of bias (because of sampling or plant identification problems). An analysis of similarities (ANOSIM) was conducted in different scales to test for differences in the repertoire of therapeutic indications treated using native and exotic species. We have found that although there is some overlap between native and exotic plants regarding their therapeutic indications and the body systems (BSs) that they treat, there are clear gaps present, that is, there are therapeutic indications and BSs treated that are exclusive to exotic species. This scenario enables the postulation of two alternative unfoldings of the diversification hypothesis, namely, (1) exotic species are initially introduced to fill gaps and undergo subsequent expansion of their use for medical purposes already addressed using native species and (2) exotic species are initially introduced to address problems already addressed using native species to diversify the repertoire of medicinal plants and to increase the resilience of medical systems. The reasons why exotic species may have a competitive advantage over the native ones, the implications of the introduction of exotic species for the resilience of medical systems, and the contexts in which autochthonous plants can gain strength to remain in pharmacopoeias are also discussed.

  8. Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality

    PubMed Central

    Sletten, Ellen M.

    2010-01-01

    The study of biomolecules in their native environments is a challenging task because of the vast complexity of cellular systems. Technologies developed in the last few years for the selective modification of biological species in living systems have yielded new insights into cellular processes. Key to these new techniques are bioorthogonal chemical reactions, whose components must react rapidly and selectively with each other under physiological conditions in the presence of the plethora of functionality necessary to sustain life. Herein we describe the bioorthogonal chemical reactions developed to date and how they can be used to study biomolecules. PMID:19714693

  9. Bioorthogonal chemistry: fishing for selectivity in a sea of functionality.

    PubMed

    Sletten, Ellen M; Bertozzi, Carolyn R

    2009-01-01

    The study of biomolecules in their native environments is a challenging task because of the vast complexity of cellular systems. Technologies developed in the last few years for the selective modification of biological species in living systems have yielded new insights into cellular processes. Key to these new techniques are bioorthogonal chemical reactions, whose components must react rapidly and selectively with each other under physiological conditions in the presence of the plethora of functionality necessary to sustain life. Herein we describe the bioorthogonal chemical reactions developed to date and how they can be used to study biomolecules.

  10. Relative Weighting of Semantic and Syntactic Cues in Native and Non-Native Listeners' Recognition of English Sentences.

    PubMed

    Shi, Lu-Feng; Koenig, Laura L

    2016-01-01

    Non-native listeners do not recognize English sentences as effectively as native listeners, especially in noise. It is not entirely clear to what extent such group differences arise from differences in relative weight of semantic versus syntactic cues. This study quantified the use and weighting of these contextual cues via Boothroyd and Nittrouer's j and k factors. The j represents the probability of recognizing sentences with or without context, whereas the k represents the degree to which context improves recognition performance. Four groups of 13 normal-hearing young adult listeners participated. One group consisted of native English monolingual (EMN) listeners, whereas the other three consisted of non-native listeners contrasting in their language dominance and first language: English-dominant Russian-English, Russian-dominant Russian-English, and Spanish-dominant Spanish-English bilinguals. All listeners were presented three sets of four-word sentences: high-predictability sentences included both semantic and syntactic cues, low-predictability sentences included syntactic cues only, and zero-predictability sentences included neither semantic nor syntactic cues. Sentences were presented at 65 dB SPL binaurally in the presence of speech-spectrum noise at +3 dB SNR. Listeners orally repeated each sentence and recognition was calculated for individual words as well as the sentence as a whole. Comparable j values across groups for high-predictability, low-predictability, and zero-predictability sentences suggested that all listeners, native and non-native, utilized contextual cues to recognize English sentences. Analysis of the k factor indicated that non-native listeners took advantage of syntax as effectively as EMN listeners. However, only English-dominant bilinguals utilized semantics to the same extent as EMN listeners; semantics did not provide a significant benefit for the two non-English-dominant groups. When combined, semantics and syntax benefitted EMN listeners significantly more than all three non-native groups of listeners. Language background influenced the use and weighting of semantic and syntactic cues in a complex manner. A native language advantage existed in the effective use of both cues combined. A language-dominance effect was seen in the use of semantics. No first-language effect was present for the use of either or both cues. For all non-native listeners, syntax contributed significantly more to sentence recognition than semantics, possibly due to the fact that semantics develops more gradually than syntax in second-language acquisition. The present study provides evidence that Boothroyd and Nittrouer's j and k factors can be successfully used to quantify the effectiveness of contextual cue use in clinically relevant, linguistically diverse populations.

  11. Intravital FRET: Probing Cellular and Tissue Function in Vivo

    PubMed Central

    Radbruch, Helena; Bremer, Daniel; Mothes, Ronja; Günther, Robert; Rinnenthal, Jan Leo; Pohlan, Julian; Ulbricht, Carolin; Hauser, Anja E.; Niesner, Raluca

    2015-01-01

    The development of intravital Förster Resonance Energy Transfer (FRET) is required to probe cellular and tissue function in the natural context: the living organism. Only in this way can biomedicine truly comprehend pathogenesis and develop effective therapeutic strategies. Here we demonstrate and discuss the advantages and pitfalls of two strategies to quantify FRET in vivo—ratiometrically and time-resolved by fluorescence lifetime imaging—and show their concrete application in the context of neuroinflammation in adult mice. PMID:26006244

  12. Antiprion activity of DB772 and related monothiophene-and furan-based analogs in a persistently infected ovine microglia culture system

    USDA-ARS?s Scientific Manuscript database

    The transmissible spongiform encephalopathies are fatal neurodegenerative disorders characterized by the misfolding of the native cellular prion protein (PrP-C) into the accumulating, disease-associated isoform (PrP-Sc). Despite extensive research into the inhibition of prion accumulation, no effect...

  13. The relationship between native allophonic experience with vowel duration and perception of the English tense/lax vowel contrast by Spanish and Russian listeners.

    PubMed

    Kondaurova, Maria V; Francis, Alexander L

    2008-12-01

    Two studies explored the role of native language use of an acoustic cue, vowel duration, in both native and non-native contexts in order to test the hypothesis that non-native listeners' reliance on vowel duration instead of vowel quality to distinguish the English tense/lax vowel contrast could be explained by the role of duration as a cue in native phonological contrasts. In the first experiment, native Russian, Spanish, and American English listeners identified stimuli from a beat/bit continuum varying in nine perceptually equal spectral and duration steps. English listeners relied predominantly on spectrum, but showed some reliance on duration. Russian and Spanish speakers relied entirely on duration. In the second experiment, three tests examined listeners' use of vowel duration in native contrasts. Duration was equally important for the perception of lexical stress for all three groups. However, English listeners relied more on duration as a cue to postvocalic consonant voicing than did native Spanish or Russian listeners, and Spanish listeners relied on duration more than did Russian listeners. Results suggest that, although allophonic experience may contribute to cross-language perceptual patterns, other factors such as the application of statistical learning mechanisms and the influence of language-independent psychoacoustic proclivities cannot be ruled out.

  14. The relationship between native allophonic experience with vowel duration and perception of the English tense∕lax vowel contrast by Spanish and Russian listeners

    PubMed Central

    Kondaurova, Maria V.; Francis, Alexander L.

    2008-01-01

    Two studies explored the role of native language use of an acoustic cue, vowel duration, in both native and non-native contexts in order to test the hypothesis that non-native listeners’ reliance on vowel duration instead of vowel quality to distinguish the English tense∕lax vowel contrast could be explained by the role of duration as a cue in native phonological contrasts. In the first experiment, native Russian, Spanish, and American English listeners identified stimuli from a beat∕bit continuum varying in nine perceptually equal spectral and duration steps. English listeners relied predominantly on spectrum, but showed some reliance on duration. Russian and Spanish speakers relied entirely on duration. In the second experiment, three tests examined listeners’ use of vowel duration in native contrasts. Duration was equally important for the perception of lexical stress for all three groups. However, English listeners relied more on duration as a cue to postvocalic consonant voicing than did native Spanish or Russian listeners, and Spanish listeners relied on duration more than did Russian listeners. Results suggest that, although allophonic experience may contribute to cross-language perceptual patterns, other factors such as the application of statistical learning mechanisms and the influence of language-independent psychoacoustic proclivities cannot be ruled out. PMID:19206820

  15. Differential Antibody Responses to Conserved HIV-1 Neutralizing Epitopes in the Context of Multivalent Scaffolds and Native-Like gp140 Trimers

    PubMed Central

    Morris, Charles D.; Azadnia, Parisa; de Val, Natalia; Vora, Nemil; Honda, Andrew; Giang, Erick; Saye-Francisco, Karen; Cheng, Yushao; Lin, Xiaohe; Mann, Colin J.; Tang, Jeffrey; Sok, Devin; Burton, Dennis R.; Law, Mansun; Ward, Andrew B.

    2017-01-01

    ABSTRACT Broadly neutralizing antibodies (bNAbs) have provided valuable insights into the humoral immune response to HIV-1. While rationally designed epitope scaffolds and well-folded gp140 trimers have been proposed as vaccine antigens, a comparative understanding of their antibody responses has not yet been established. In this study, we probed antibody responses to the N332 supersite and the membrane-proximal external region (MPER) in the context of heterologous protein scaffolds and native-like gp140 trimers. Ferritin nanoparticles and fragment crystallizable (Fc) regions were utilized as multivalent carriers to display scaffold antigens with grafted N332 and MPER epitopes, respectively. Trimeric scaffolds were also identified to stabilize the MPER-containing BG505 gp140.681 trimer in a native-like conformation. Following structural and antigenic evaluation, a subset of scaffold and trimer antigens was selected for immunization in BALB/c mice. Serum binding revealed distinct patterns of antibody responses to these two bNAb targets presented in different structural contexts. For example, the N332 nanoparticles elicited glycan epitope-specific antibody responses that could also recognize the native trimer, while a scaffolded BG505 gp140.681 trimer generated a stronger and more rapid antibody response to the trimer apex than its parent gp140.664 trimer. Furthermore, next-generation sequencing (NGS) of mouse splenic B cells revealed expansion of antibody lineages with long heavy-chain complementarity-determining region 3 (HCDR3) loops upon activation by MPER scaffolds, in contrast to the steady repertoires primed by N332 nanoparticles and a soluble gp140.664 trimer. These findings will facilitate the future development of a coherent vaccination strategy that combines both epitope-focused and trimer-based approaches. PMID:28246356

  16. Limited impact of an invasive oyster on intertidal assemblage structure and biodiversity: the importance of environmental context and functional equivalency with native species.

    PubMed

    Zwerschke, Nadescha; Hollyman, Philip R; Wild, Romy; Strigner, Robin; Turner, John R; King, Jonathan W

    2018-01-01

    Impacts of invasive species are context dependent and linked to the ecosystem they occur within. To broaden the understanding of the impact of a globally widespread invasive oyster, Crassostrea ( Magallana ) gigas, intertidal surveys were carried out at 15 different sites in Europe. The impact of C. gigas on macro- (taxa surrounding oyster > 1 cm) and epifaunal (taxa on oyster < 1 cm) benthic communities and α and β-diversity was assessed and compared to those associated with native ecosystem engineers, including the flat oyster Ostrea edulis . Whilst the effect of C. gigas on benthic community structures was dependent on habitat type, epifaunal communities associated with low densities of O. edulis and C. gigas did not differ and changes in benthic assemblage structure owing to the abundance of C. gigas were therefore attributed to the presence of oyster shells. Macrofaunal α-diversity increased with C. gigas cover in muddy habitats, while epifaunal α-diversity decreased at greater oyster densities. Macrofaunal β-diversity was greatest at low densities of C. gigas ; however, it did not differ between samples without and increased densities of oysters. In contrast, epifaunal β-diversity decreased with increasing oyster cover. Different environmental contexts enabled more independent predictions of the effect of C. gigas on native communities. These were found to be low and more importantly not differing from O. edulis . This indicates that, at low densities, C. gigas may be functionally equivalent to the declining native oyster in terms of biodiversity facilitation and aid in re-establishing benthic communities on shores where O. edulis has become extinct.

  17. Context Effects and Spoken Word Recognition of Chinese: An Eye-Tracking Study

    ERIC Educational Resources Information Center

    Yip, Michael C. W.; Zhai, Mingjun

    2018-01-01

    This study examined the time-course of context effects on spoken word recognition during Chinese sentence processing. We recruited 60 native Mandarin listeners to participate in an eye-tracking experiment. In this eye-tracking experiment, listeners were told to listen to a sentence carefully, which ended with a Chinese homophone, and look at…

  18. Symmetrical and Asymmetrical Scaffolding of L2 Collocations in the Context of Concordancing

    ERIC Educational Resources Information Center

    Rezaee, Abbas Ali; Marefat, Hamideh; Saeedakhtar, Afsaneh

    2015-01-01

    Collocational competence is recognized to be integral to native-like L2 performance, and concordancing can be of assistance in gaining this competence. This study reports on an investigation into the effect of symmetrical and asymmetrical scaffolding on the collocational competence of Iranian intermediate learners of English in the context of…

  19. Functional Neuroanatomy of Contextual Acquisition of Concrete and Abstract Words

    ERIC Educational Resources Information Center

    Mestres-Misse, Anna; Munte, Thomas F.; Rodriguez-Fornells, Antoni

    2009-01-01

    The meaning of a novel word can be acquired by extracting it from linguistic context. Here we simulated word learning of new words associated to concrete and abstract concepts in a variant of the human simulation paradigm that provided linguistic context information in order to characterize the brain systems involved. Native speakers of Spanish…

  20. Perennial grass and native wildflowers: a synergistic approach to habitat management

    USDA-ARS?s Scientific Manuscript database

    A total of 19 buffer plots were established on University of Georgia experimental farms and lands near Tifton, GA in 2015. The buffer plots were assigned to a 2 x 2 design of local spatial context and irrigation. For local spatial context, ten plots were located adjacent to woodland (“T”) and ten in...

  1. Lexical Competition during Second-Language Listening: Sentence Context, but Not Proficiency, Constrains Interference from the Native Lexicon

    ERIC Educational Resources Information Center

    Chambers, Craig G.; Cooke, Hilary

    2009-01-01

    A spoken language eye-tracking methodology was used to evaluate the effects of sentence context and proficiency on parallel language activation during spoken language comprehension. Nonnative speakers with varying proficiency levels viewed visual displays while listening to French sentences (e.g., "Marie va decrire la poule" [Marie will…

  2. Nanoscale visualization and characterization of Myxococcus xanthus cells with atomic force microscopy

    PubMed Central

    Pelling, Andrew E.; Li, Yinuo; Shi, Wenyuan; Gimzewski, James K.

    2005-01-01

    Multicellular microbial communities are the predominant form of existence for microorganisms in nature. As one of the most primitive social organisms, Myxococcus xanthus has been an ideal model bacterium for studying intercellular interaction and multicellular organization. Through previous genetic and EM studies, various extracellular appendages and matrix components have been found to be involved in the social behavior of M. xanthus, but none of them was directly visualized and analyzed under native conditions. Here, we used atomic force microscopy (AFM) imaging and in vivo force spectroscopy to characterize these cellular structures under native conditions. AFM imaging revealed morphological details on the extracellular ultrastructures at an unprecedented resolution, and in vivo force spectroscopy of live cells in fluid allowed us to nanomechanically characterize extracellular polymeric substances. The findings provide the basis for AFM as a useful tool for investigating microbial-surface ultrastructures and nanomechanical properties under native conditions. PMID:15840722

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

    Law, Anthony B.; Sapienza, Paul J.; Zhang, Jun

    Allostery enables tight regulation of protein function in the cellular environment. While existing models of allostery are firmly rooted in the current structure-function paradigm, the mechanistic basis for allostery in the absence of structural change remains unclear. In this study, we show that a typical globular protein is able to undergo significant changes in volume under native conditions while exhibiting no additional changes in protein structure. These native state volume fluctuations were found to correlate with changes in internal motions that were previously recognized as a source of allosteric entropy. This finding offers a novel mechanistic basis for allostery inmore » the absence of canonical structural change. As a result, the unexpected observation that function can be derived from expanded, low density protein states has broad implications for our understanding of allostery and suggests that the general concept of the native state be expanded to allow for more variable physical dimensions with looser packing.« less

  4. Technology Learning Activities: Columbus Sailed the Ocean Blue, the Cellular Connection, Emergency Shelter.

    ERIC Educational Resources Information Center

    Etchison, Cindy; Deal, Walter F., III

    1992-01-01

    Presents learning activities such as planning and building a sailboat, manufacturing cellular phone cases, and designing and building emergency shelters. Includes the context, the challenge, resources used, objectives, materials needed, and an evaluation. (JOW)

  5. Are Invasive Species Stressful? The Glucocorticoid Profile of Native Lizards Exposed to Invasive Fire Ants Depends on the Context.

    PubMed

    Graham, Sean P; Freidenfelds, Nicole A; Thawley, Christopher J; Robbins, Travis R; Langkilde, Tracy

    Invasive species represent a substantial threat to native species worldwide. Research on the impacts of invasive species on wild living vertebrates has focused primarily on population-level effects. The sublethal, individual-level effects of invaders may be equally important but are poorly understood. We investigated the effects of invasive fire ants (Solenopsis invicta) on the physiological stress response of a native lizard (Sceloporus undulatus) within two experimental contexts: directly exposing lizards to a fire ant attack and housing lizards with fire ants in seminatural field enclosures. Lizards directly exposed to brief attack by fire ants had elevated concentrations of the stress hormone corticosterone (CORT), suggesting that these encounters can be physiologically stressful. However, lizards exposed for longer periods to fire ants in field enclosures had lower concentrations of CORT. This may indicate that the combined effects of confinement and fire ant exposure have pushed lizards into allostatic overload. However, lizards from fire ant enclosures appeared to have intact negative feedback controls of the stress response, evidenced by functioning adrenocorticotropic hormone responsiveness and lack of suppression of innate immunity (plasma bactericidal capacity). We review previous studies examining the stress response of wild vertebrates to various anthropogenic stressors and discuss how these-in combination with our results-underscore the importance of considering context (the length, frequency, magnitude, and types of threat) when assessing these impacts.

  6. Non-native Soluble Oligomers of Cu/Zn Superoxide Dismutase (SOD1) Contain a Conformational Epitope Linked to Cytotoxicity in Amyotrophic Lateral Sclerosis (ALS)

    PubMed Central

    2015-01-01

    Soluble misfolded Cu/Zn superoxide dismutase (SOD1) is implicated in motor neuron death in amyotrophic lateral sclerosis (ALS); however, the relative toxicities of the various non-native species formed by SOD1 as it misfolds and aggregates are unknown. Here, we demonstrate that early stages of SOD1 aggregation involve the formation of soluble oligomers that contain an epitope specific to disease-relevant misfolded SOD1; this epitope, recognized by the C4F6 antibody, has been proposed as a marker of toxic species. Formation of potentially toxic oligomers is likely to be exacerbated by an oxidizing cellular environment, as evidenced by increased oligomerization propensity and C4F6 reactivity when oxidative modification by glutathione is present at Cys-111. These findings suggest that soluble non-native SOD1 oligomers, rather than native-like dimers or monomers, share structural similarity to pathogenic misfolded species found in ALS patients and therefore represent potential cytotoxic agents and therapeutic targets in ALS. PMID:24660965

  7. Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriers.

    PubMed

    Wang, Fengling; Chen, Jin; Dai, Wenting; He, Zhengmin; Zhai, Dandan; Chen, Weidong

    2017-09-01

    In order to investigate the potential of nanostructured lipid carriers for efficient and targeted delivery of curcumin, the pharmacokinetic parameters of curcumin-loaded nanostructured lipid carriers (Cur-NLC) were evaluated in rats after a single intraperitoneal dose of Cur-NLC. In addition, the anticancer activity of Cur-NLC against human lung adenocarcinoma A549 cells was verified by a cellular uptake study, and a cytotoxicity and apoptosis assay. Bioavailability of Cur-NLC was better than that of native curcumin (p > 0.01), as seen from the area under the plasma concentration-time curve (AUC), maximum plasma concentration (Cmax), mean residence time (MRT) and total plasma clearance (CLz/F). Cur-NLC has a more obvious lung-targeting property in comparison with native curcumin. Cur-NLC showed higher anticancer activity in vitro against A549 cells than native curcumin (IC50 value of 5.66 vs. 9.81 mg L-1, respectively). Meanwhile, Cur-NLC treated A549 cells showed a higher apoptosis rate compared to that of native curcumin. These results indicate that NLC is a promising system for the delivery of curcumin in the treatment of lung adenocarcinoma.

  8. Integration of Stem Cell to Chondrocyte-Derived Cartilage Matrix in Healthy and Osteoarthritic States in the Presence of Hydroxyapatite Nanoparticles.

    PubMed

    Dua, Rupak; Comella, Kristin; Butler, Ryan; Castellanos, Glenda; Brazille, Bryn; Claude, Andrew; Agarwal, Arvind; Liao, Jun; Ramaswamy, Sharan

    2016-01-01

    We investigated the effectiveness of integrating tissue engineered cartilage derived from human bone marrow derived stem cells (HBMSCs) to healthy as well as osteoarthritic cartilage mimics using hydroxyapatite (HA) nanoparticles immersed within a hydrogel substrate. Healthy and diseased engineered cartilage from human chondrocytes (cultured in agar gels) were integrated with human bone marrow stem cell (HBMSC)-derived cartilaginous engineered matrix with and without HA, and evaluated after 28 days of growth. HBMSCs were seeded within photopolymerizable poly (ethylene glycol) diacrylate (PEGDA) hydrogels. In addition, we also conducted a preliminary in vivo evaluation of cartilage repair in rabbit knee chondral defects treated with subchondral bone microfracture and cell-free PEGDA with and without HA. Under in vitro conditions, the interfacial shear strength between tissue engineered cartilage derived from HBMSCs and osteoarthritic chondrocytes was significantly higher (p < 0.05) when HA nanoparticles were incorporated within the HBMSC culture system. Histological evidence confirmed a distinct spatial transition zone, rich in calcium phosphate deposits. Assessment of explanted rabbit knees by histology demonstrated that cellularity within the repair tissues that had filled the defects were of significantly higher number (p < 0.05) when HA was used. HA nanoparticles play an important role in treating chondral defects when osteoarthritis is a co-morbidity. We speculate that the calcified layer formation at the interface in the osteoarthritic environment in the presence of HA is likely to have attributed to higher interfacial strength found in vitro. From an in vivo standpoint, the presence of HA promoted cellularity in the tissues that subsequently filled the chondral defects. This higher presence of cells can be considered important in the context of accelerating long-term cartilage remodeling. We conclude that HA nanoparticles play an important role in engineered to native cartilage integration and cellular processes.

  9. Transgenic banana plants overexpressing a native plasma membrane aquaporin MusaPIP1;2 display high tolerance levels to different abiotic stresses.

    PubMed

    Sreedharan, Shareena; Shekhawat, Upendra K S; Ganapathi, Thumballi R

    2013-10-01

    Water transport across cellular membranes is regulated by a family of water channel proteins known as aquaporins (AQPs). As most abiotic stresses like suboptimal temperatures, drought or salinity result in cellular dehydration, it is imperative to study the cause-effect relationship between AQPs and the cellular consequences of abiotic stress stimuli. Although plant cells have a high isoform diversity of AQPs, the individual and integrated roles of individual AQPs in optimal and suboptimal physiological conditions remain unclear. Herein, we have identified a plasma membrane intrinsic protein gene (MusaPIP1;2) from banana and characterized it by overexpression in transgenic banana plants. Cellular localization assay performed using MusaPIP1;2::GFP fusion protein indicated that MusaPIP1;2 translocated to plasma membrane in transformed banana cells. Transgenic banana plants overexpressing MusaPIP1;2 constitutively displayed better abiotic stress survival characteristics. The transgenic lines had lower malondialdehyde levels, elevated proline and relative water content and higher photosynthetic efficiency as compared to equivalent controls under different abiotic stress conditions. Greenhouse-maintained hardened transgenic plants showed faster recovery towards normal growth and development after cessation of abiotic stress stimuli, thereby underlining the importance of these plants in actual environmental conditions wherein the stress stimuli is often transient but severe. Further, transgenic plants where the overexpression of MusaPIP1;2 was made conditional by tagging it with a stress-inducible native dehydrin promoter also showed similar stress tolerance characteristics in in vitro and in vivo assays. Plants developed in this study could potentially enable banana cultivation in areas where adverse environmental conditions hitherto preclude commercial banana cultivation. © 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  10. A Sociolinguistic Study of Meaning-Making in a Nigerian Linguistic Landscape: The Example of Ibadan

    ERIC Educational Resources Information Center

    Adetunji, Akinbiyi

    2013-01-01

    Although much research has gone into the sociolinguistics of the linguistic landscape (space for and language of public signs) in the "peripheral," non-native contexts of English Language use and users, none has been specifically devoted to a Nigerian context. This dissertation is intended to fill this wide gap. Focusing on the Ibadan…

  11. Unrestricted Territory: Gender, Two Spirits, and Louise Erdrich's "The Last Report on the Miracles at Little No Horse"

    ERIC Educational Resources Information Center

    Keenan, Deirdre

    2006-01-01

    In this article, the author examines Louise Erdrich's representation of Father Damien in "The Last Report on the Miracles at Little No Horse" in the context of mainstream attitudes about transgender identities and Native American gender systems. In this context, Erdrich's novel provides a theory and practice of gender identity formation that…

  12. Explicit and Implicit Feedback, Modified Output, and SLA: Does Explicit and Implicit Feedback Promote Learning and Learner-Learner Interactions?

    ERIC Educational Resources Information Center

    Adams, Rebecca; Nuevo, Ana Maria; Egi, Takako

    2011-01-01

    Research on interactional feedback has typically focused on feedback learners receive from native speakers (i.e., NS-learner contexts). However, for many second language (L2) learners, the majority of their opportunities to engage in interaction occur with other learners (i.e., learner-learner contexts). The literature has suggested that feedback…

  13. Uncovering the Motivating Factors behind Writing in English in en EFL Context

    ERIC Educational Resources Information Center

    Büyükyavuz, Oya; Çakir, Ismail

    2014-01-01

    Writing in a language, whether the target or native, is regarded as a complex activity operating on multiple cognitive levels. This study aimed to uncover the factors which motivate teacher trainees of English to write in English in an EFL context. The study also investigated the differences in the ways teacher trainees are motivated in terms of…

  14. The Role of Vowels in Reading Semitic Scripts: Data from Arabic and Hebrew.

    ERIC Educational Resources Information Center

    Abu-Rabia, Salim

    2001-01-01

    Investigates the effect of vowels and context on reading accuracy of skilled adult native Arabic speakers in Arabic and in Hebrew, their second language. Reveals a significant effect for vowels and for context across all reading conditions in Arabic and Hebrew. Finds that the vowelized texts in Arabic and the pointed and unpointed texts in Hebrew…

  15. Perceptual prothesis in native Spanish speakers

    NASA Astrophysics Data System (ADS)

    Theodore, Rachel M.; Schmidt, Anna M.

    2003-04-01

    Previous research suggests a perceptual bias exists for native phonotactics [D. Massaro and M. Cohen, Percept. Psychophys. 34, 338-348 (1983)] such that listeners report nonexistent segments when listening to stimuli that violate native phonotactics [E. Dupoux, K. Kakehi, Y. Hirose, C. Pallier, and J. Mehler, J. Exp. Psychol.: Human Percept. Perform. 25, 1568-1578 (1999)]. This study investigated how native-language experience affects second language processing, focusing on how native Spanish speakers perceive the English clusters /st/, /sp/, and /sk/, which represent phonotactically illegal forms in Spanish. To preserve native phonotactics, Spanish speakers often produce prothetic vowels before English words beginning with /s/ clusters. Is the influence of native phonotactics also present in the perception of illegal clusters? A stimuli continuum ranging from no vowel (e.g., ``sku'') to a full vowel (e.g., ``esku'') before the cluster was used. Four final vowel contexts were used for each cluster, resulting in 12 sCV and 12 VsCV nonword endpoints. English and Spanish listeners were asked to discriminate between pairs differing in vowel duration and to identify the presence or absence of a vowel before the cluster. Results will be discussed in terms of implications for theories of second language speech perception.

  16. Quality of life of Portuguese and Spanish adolescents. A comparative study between natives and immigrants.

    PubMed

    Nunes, Cristina; Hernando, Ángel; Lemos, Ida; Ayala-Nunes, Lara; Oliva, Cristina Romero; Coronado, Cecilia Montilla

    2016-04-01

    The aim of this study was to analyse differences in quality of life (QOL) between Spanish and Portuguese immigrant and native adolescents. In total, 475 native and immigrant adolescents (52% boys) from Algarve (Portugal) and Huelva (Spain), aged between 12 and 17 years old, were assessed with the KIDSCREEN-52. QOL dimensions were not related to most academic variables, with the exception of number of school failures, Financial Resources and Social Support from Peers. Multivariate analysis of variance (MANOVA) was used to examine statistical differences in adolescents QOL. Age differences in QOL levels were not found. Girls reported worse QOL levels on Physical Wellbeing than boys (F = 10.32, p = .001, η2 =.02). Immigrant Portuguese adolescents scored higher on Mood (F = 17.57, p = .000, η2 =.11), and native Portuguese adolescents scored higher on Social Acceptance (F = 4.87, p = .002, η2=.033). Immigrant and native adolescents had similar levels of perceived QOL. Overall, it seems that in both countries, the living contexts for immigrant and native adolescents are fairly homogeneous.

  17. The Politics of Native American Health Care and the Affordable Care Act.

    PubMed

    Skinner, Daniel

    2016-02-01

    This article examines an important but largely overlooked dimension of the Patient Protection and Affordable Care Act (ACA), namely, its significance for Native American health care. The author maintains that reading the ACA against the politics of Native American health care policy shows that, depending on their regional needs and particular contexts, many Native Americans are well-placed to benefit from recent Obama-era reforms. At the same time, the kinds of options made available by the ACA constitute a departure from the service-based (as opposed to insurance-based) Indian Health Service (IHS). Accordingly, the author argues that ACA reforms--private marketplaces, Medicaid expansion, and accommodations for Native Americans--are best read as potential "supplements" to an underfunded IHS. Whether or not Native Americans opt to explore options under the ACA will depend in the long run on the quality of the IHS in the post-ACA era. Beyond understanding the ACA in relation to IHS funding, the author explores how Native American politics interacts with the key tenets of Obama-era health care reform--especially "affordability"--which is critical for understanding what is required from and appropriate to future Native American health care policy making. Copyright © 2016 by Duke University Press.

  18. Plant functional traits of dominant native and invasive species in mediterranean-climate ecosystems.

    PubMed

    Funk, Jennifer L; Standish, Rachel J; Stock, William D; Valladares, Fernando

    2016-01-01

    The idea that dominant invasive plant species outperform neighboring native species through higher rates of carbon assimilation and growth is supported by several analyses of global data sets. However, theory suggests that native and invasive species occurring in low-resource environments will be functionally similar, as environmental factors restrict the range of observed physiological and morphological trait values. We measured resource-use traits in native and invasive plant species across eight diverse vegetation communities distributed throughout the five mediterranean-climate regions, which are drought prone and increasingly threatened by human activities, including the introduction of exotic species. Traits differed strongly across the five regions. In regions with functional differences between native and invasive species groups, invasive species displayed traits consistent with high resource acquisition; however, these patterns were largely attributable to differences in life form. We found that species invading mediterranean-climate regions were more likely to be annual than perennial: three of the five regions were dominated by native woody species and invasive annuals. These results suggest that trait differences between native and invasive species are context dependent and will vary across vegetation communities. Native and invasive species within annual and perennial groups had similar patterns of carbon assimilation and resource use, which contradicts the widespread idea that invasive species optimize resource acquisition rather than resource conservation. .

  19. Bioinvasive species and the preservation of cutthroat trout in the western United States: Ecological, social, and economic issues

    USGS Publications Warehouse

    Quist, M.C.; Hubert, W.A.

    2004-01-01

    The cutthroat trout (Oncorhynchus clarki) was the only endemic salmonid species across most of the western United States, and it has severely declined largely due to introduction and bioinvasion by non-native salmonid species. However, the ecological, social, and economic consequences of cutthroat trout declines and replacement by non-native salmonid species are relatively minor, and measurable affects on ecosystem function are rare. Restoration efforts for cutthroat trout involve removal or control of bioinvasive salmonid species, but such efforts are costly, ongoing, and resisted frequently by segments of society. Cutthroat trout declines are of little concern to much of the public because they are valued similarly to non-native salmonids, and non-native salmonid species frequently have higher recreational values. Due to the low values placed on cutthroat trout relative to non-native salmonid species, net economic benefits of preserving cutthroat trout are equal to or less than those for non-native salmonids. Cutthroat trout provide a classic case of the consequences of biological invasion; however, other native species are faced with similar issues. We suggest that management agencies establish realistic goals to preserve native species within the context of ecological, social, and economic issues. ?? 2004 Elsevier Ltd. All rights reserved.

  20. Linking Native and Invader Traits Explains Native Spider Population Responses to Plant Invasion.

    PubMed

    Smith, Jennifer N; Emlen, Douglas J; Pearson, Dean E

    2016-01-01

    Theoretically, the functional traits of native species should determine how natives respond to invader-driven changes. To explore this idea, we simulated a large-scale plant invasion using dead spotted knapweed (Centaurea stoebe) stems to determine if native spiders' web-building behaviors could explain differences in spider population responses to structural changes arising from C. stoebe invasion. After two years, irregular web-spiders were >30 times more abundant and orb weavers were >23 times more abundant on simulated invasion plots compared to controls. Additionally, irregular web-spiders on simulated invasion plots built webs that were 4.4 times larger and 5.0 times more likely to capture prey, leading to >2-fold increases in recruitment. Orb-weavers showed no differences in web size or prey captures between treatments. Web-spider responses to simulated invasion mimicked patterns following natural invasions, confirming that C. stoebe's architecture is likely the primary attribute driving native spider responses to these invasions. Differences in spider responses were attributable to differences in web construction behaviors relative to historic web substrate constraints. Orb-weavers in this system constructed webs between multiple plants, so they were limited by the overall quantity of native substrates but not by the architecture of individual native plant species. Irregular web-spiders built their webs within individual plants and were greatly constrained by the diminutive architecture of native plant substrates, so they were limited both by quantity and quality of native substrates. Evaluating native species traits in the context of invader-driven change can explain invasion outcomes and help to identify factors limiting native populations.

  1. Linking Native and Invader Traits Explains Native Spider Population Responses to Plant Invasion

    PubMed Central

    Emlen, Douglas J.; Pearson, Dean E.

    2016-01-01

    Theoretically, the functional traits of native species should determine how natives respond to invader-driven changes. To explore this idea, we simulated a large-scale plant invasion using dead spotted knapweed (Centaurea stoebe) stems to determine if native spiders’ web-building behaviors could explain differences in spider population responses to structural changes arising from C. stoebe invasion. After two years, irregular web-spiders were >30 times more abundant and orb weavers were >23 times more abundant on simulated invasion plots compared to controls. Additionally, irregular web-spiders on simulated invasion plots built webs that were 4.4 times larger and 5.0 times more likely to capture prey, leading to >2-fold increases in recruitment. Orb-weavers showed no differences in web size or prey captures between treatments. Web-spider responses to simulated invasion mimicked patterns following natural invasions, confirming that C. stoebe’s architecture is likely the primary attribute driving native spider responses to these invasions. Differences in spider responses were attributable to differences in web construction behaviors relative to historic web substrate constraints. Orb-weavers in this system constructed webs between multiple plants, so they were limited by the overall quantity of native substrates but not by the architecture of individual native plant species. Irregular web-spiders built their webs within individual plants and were greatly constrained by the diminutive architecture of native plant substrates, so they were limited both by quantity and quality of native substrates. Evaluating native species traits in the context of invader-driven change can explain invasion outcomes and help to identify factors limiting native populations. PMID:27082240

  2. Publication Ethics and the Emerging Scientific Workforce: Understanding ‘Plagiarism’ in a Global Context

    PubMed Central

    Cameron, Carrie; Zhao, Hui; McHugh, Michelle K.

    2013-01-01

    Scientific publication has long been dominated by the English language and is rapidly moving towards near complete hegemony of English, while the majority of the world’s publishing scientists are not native English speakers. This imbalance has important implications for training in and enforcement of publication ethics, particularly with respect to plagiarism. A lack of understanding of what constitutes plagiarism and the use of a linguistic support strategy known as patchwriting can lead to inadvertent misuse of source material by non-native speakers writing in English as well as to unfounded accusations of intentional scientific misconduct on the part of these authors. A rational and well-informed dialogue about this issue is needed among both native English speaking and non-native English speaking writers, editors, educators, and administrators. Recommendations for educating and training are provided. PMID:22104051

  3. Freezing/Thawing without Cryoprotectant Damages Native but not Decellularized Porcine Renal Tissue

    PubMed Central

    Poornejad, Nafiseh; Frost, Timothy S; Scott, Daniel R; Elton, Brinden B; Reynolds, Paul R; Roeder, Beverly L; Cook, Alonzo D

    2015-01-01

    abstract Whole organ decellularization of porcine renal tissue and recellularization with a patient's own cells would potentially overcome immunorejection, which is one of the most significant problems with allogeneic kidney transplantation. However, there are obstacles to achieving this goal, including preservation of the decellularized extracellular matrix (ECM), identifying the proper cell types, and repopulating the ECM before transplantation. Freezing biological tissue is the best option to avoid spoilage; however, it may damage the structure of the tissue or disrupt cellular membranes through ice crystal formation. Cryoprotectants have been used to repress ice formation during freezing, although cell toxicity can still occur. The effect of freezing/thawing on native (n = 10) and decellularized (n = 10) whole porcine kidneys was studied without using cryoprotectants. Results showed that the elastic modulus of native kidneys was reduced by a factor of 22 (P < 0.0001) by freezing/thawing or decellularization, while the elastic modulus for decellularized ECM was essentially unchanged by the freezing/thawing process (p = 0.0636). Arterial pressure, representative of structural integrity, was also reduced by a factor of 52 (P < 0.0001) after freezing/thawing for native kidneys, compared to a factor of 43 (P < 0.0001) for decellularization and a factor of 4 (P < 0.0001) for freezing/thawing decellularized structures. Both freezing/thawing and decellularization reduced stiffness, but the reductions were not additive. Investigation of the microstructure of frozen/thawed native and decellularized renal tissues showed increased porosity due to cell removal and ice crystal formation. Orcein and Sirius staining showed partial damage to elastic and collagen fibers after freezing/thawing. It was concluded that cellular damage and removal was more responsible for reducing stiffness than fibril destruction. Cell viability and growth were demonstrated on decellularized frozen/thawed and non-frozen samples using human renal cortical tubular epithelial (RCTE) cells over 12 d. No adverse effect on the ability to recellularize after freezing/thawing was observed. It is recommended that porcine kidneys be frozen prior to decellularization to prevent contamination, and after decellularization to prevent protein denaturation. Cryoprotectants may still be necessary, however, during storage and transportation after recellularization. PMID:25730294

  4. Long-term culture of bovine nucleus pulposus explants in a native environment.

    PubMed

    van Dijk, Bart G M; Potier, Esther; Ito, Keita

    2013-04-01

    Chronic low back pain is a disease with tremendous financial and social implications, and it is often caused by intervertebral disc degeneration. Regenerative therapies for disc repair are promising treatments, but they need to be tested in physiological models. To develop a physiological in vitro explant model that incorporates the native environment of the intervertebral disc, for example, hypoxia, low glucose, and high tissue osmolarity. Bovine nucleus pulposus (NP) explants were cultured for 42 days in conditions mimicking the native physiological environment. Two different approaches were used to balance the swelling pressure of the NP: raised medium osmolarity or an artificial annulus. Bovine NP explants were either cultured in media with osmolarity balanced at isotonic and hypertonic levels compared with the native tissue or cultured inside a fiber jacket used as an artificial annulus. Oxygen and glucose levels were set at either standard (21% O2 and 4.5 g/L glucose) or physiological (5% O2 and 1 g/L glucose) levels. Samples were analyzed at Day 0, 3, and 42 for tissue composition (water, sulfated glycosaminoglycans, DNA, and hydroxyproline contents and fixed charge density), tissue histology, cell viability, and cellular behavior with messenger RNA (mRNA) expression. Both the hypertonic culture and the artificial annulus approach maintained the tissue matrix composition for 42 days. At Day 3, mRNA expressions of aggrecan, collagen Type I, and collagen Type II in both hypertonic and artificial annulus cultures were not different from Day 0; however, at Day 42, the artificial annulus preserved the mRNA expression closer to Day 0. Gene expressions of matrix metalloprotease 13, tissue inhibitor of matrix metalloprotease 1, and tissue inhibitor of matrix metalloprotease 2 were downregulated under physiological O2 and glucose levels, whereas the other parameters analyzed were not affected. Although the hypertonic culture and the artificial annulus approach are both promising models to test regenerative therapies, the artificial annulus was better able to maintain a cellular behavior closer to the native tissue in longer term cultures. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Proteomic differences between native and tissue‐engineered tendon and ligament

    PubMed Central

    Tew, Simon R.; Peffers, Mandy; Canty‐Laird, Elizabeth G.; Comerford, Eithne

    2016-01-01

    Tendons and ligaments (T/Ls) play key roles in the musculoskeletal system, but they are susceptible to traumatic or age‐related rupture, leading to severe morbidity as well as increased susceptibility to degenerative joint diseases such as osteoarthritis. Tissue engineering represents an attractive therapeutic approach to treating T/L injury but it is hampered by our poor understanding of the defining characteristics of the two tissues. The present study aimed to determine differences in the proteomic profile between native T/Ls and tissue engineered (TE) T/L constructs. The canine long digital extensor tendon and anterior cruciate ligament were analyzed along with 3D TE fibrin‐based constructs created from their cells. Native tendon and ligament differed in their content of key structural proteins, with the ligament being more abundant in fibrocartilaginous proteins. 3D T/L TE constructs contained less extracellular matrix (ECM) proteins and had a greater proportion of cellular‐associated proteins than native tissue, corresponding to their low collagen and high DNA content. Constructs were able to recapitulate native T/L tissue characteristics particularly with regard to ECM proteins. However, 3D T/L TE constructs had similar ECM and cellular protein compositions indicating that cell source may not be an important factor for T/L tissue engineering. PMID:27080496

  6. Bioengineered vascular constructs as living models for in vitro cardiovascular research.

    PubMed

    Wolf, Frederic; Vogt, Felix; Schmitz-Rode, Thomas; Jockenhoevel, Stefan; Mela, Petra

    2016-09-01

    Cardiovascular diseases represent the most common cause of morbidity and mortality worldwide. In this review, we explore the potential of bioengineered vascular constructs as living models for in vitro cardiovascular research to advance the current knowledge of pathophysiological processes and support the development of clinical therapies. Bioengineered vascular constructs capable of recapitulating the cellular and mechanical environment of native vessels represent a valuable platform to study cellular interactions and signaling cascades, test drugs and medical devices under (patho)physiological conditions, with the additional potential benefit of reducing the number of animals required for preclinical testing. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Effect of gangliosides in the autoimmune response induced by liposome-associated antigens.

    PubMed

    Correa, S G; Rivero, V E; Yranzo-Volonté, N; Romero-Piffiguer, M; Ferro, M E; Riera, C M

    1993-01-01

    A model of autoimmunity to rat male accessory glands (RAG) was recently developed by intraperitoneal administration of three doses of native RAG associated with liposomes. In this work we analysed the effects of gangliosides in the cellular response to RAG when they were intraperitoneally administrated prior to the second dose of liposome-associated RAG. Results show that the ganglioside treatment could modify an established DTH response. Also, gangliosides markedly reduced the number of Ia antigen-positive peritoneal exudated cells (PEC). However, they modified neither the processing of liposomes through PEC nor their viability. Moreover, we obtained cellular response by transferring PEC from immunized donors into naive receptors.

  8. Migrant children and migrants’ children: Nativity differences in school enrollment in Mexico and the United States

    PubMed Central

    Glick, Jennifer E.; Yabiku, Scott T.

    2016-01-01

    BACKGROUND The growing prevalence of migrant children in diverse contexts requires a reconsideration of the intergenerational consequences of migration. To understand how migration and duration of residence are associated with children’s schooling, we need more comparative work that can point to the similarities and differences in outcomes for children across contexts. OBJECTIVE This paper addresses the importance of nativity and duration of residence for children’s school enrollment on both sides of a binational migration system: The United States and Mexico. The analyses are designed to determine whether duration of residence has a similar association with school enrollment across these different settings. METHODS The analyses are based on nationally representative household data from the 2010 Mexican Census and the 2006–2010 American Community Survey. Logistic regression models compare school enrollment patterns of Mexican and U.S.-born children of Mexican origin in the United States and those of Mexican and U.S.-born children in Mexico. Interactions for nativity/duration of residence and age are also included. RESULTS The results demonstrate that, adjusting for household resources and household-level migration experience, Mexican-born children in the United States and U.S.-born children in Mexico, particularly those who arrived recently, lag behind in school enrollment. These differences are most pronounced at older ages. CONCLUSIONS The comparisons across migration contexts point to greater school attrition and non-enrollment among older, recent migrant youth, regardless of the context. The interactions suggest that recent migration is associated with lower schooling for youth who engage in migration at older ages in both the United States and Mexico. PMID:28077926

  9. Protein folding by NMR.

    PubMed

    Zhuravleva, Anastasia; Korzhnev, Dmitry M

    2017-05-01

    Protein folding is a highly complex process proceeding through a number of disordered and partially folded nonnative states with various degrees of structural organization. These transiently and sparsely populated species on the protein folding energy landscape play crucial roles in driving folding toward the native conformation, yet some of these nonnative states may also serve as precursors for protein misfolding and aggregation associated with a range of devastating diseases, including neuro-degeneration, diabetes and cancer. Therefore, in vivo protein folding is often reshaped co- and post-translationally through interactions with the ribosome, molecular chaperones and/or other cellular components. Owing to developments in instrumentation and methodology, solution NMR spectroscopy has emerged as the central experimental approach for the detailed characterization of the complex protein folding processes in vitro and in vivo. NMR relaxation dispersion and saturation transfer methods provide the means for a detailed characterization of protein folding kinetics and thermodynamics under native-like conditions, as well as modeling high-resolution structures of weakly populated short-lived conformational states on the protein folding energy landscape. Continuing development of isotope labeling strategies and NMR methods to probe high molecular weight protein assemblies, along with advances of in-cell NMR, have recently allowed protein folding to be studied in the context of ribosome-nascent chain complexes and molecular chaperones, and even inside living cells. Here we review solution NMR approaches to investigate the protein folding energy landscape, and discuss selected applications of NMR methodology to studying protein folding in vitro and in vivo. Together, these examples highlight a vast potential of solution NMR in providing atomistic insights into molecular mechanisms of protein folding and homeostasis in health and disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Oxidation of an Exposed Methionine Instigates the Aggregation of Glyceraldehyde-3-phosphate Dehydrogenase*

    PubMed Central

    Samson, Andre L.; Knaupp, Anja S.; Kass, Itamar; Kleifeld, Oded; Marijanovic, Emilia M.; Hughes, Victoria A.; Lupton, Chris J.; Buckle, Ashley M.; Bottomley, Stephen P.; Medcalf, Robert L.

    2014-01-01

    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a ubiquitous and abundant protein that participates in cellular energy production. GAPDH normally exists in a soluble form; however, following necrosis, GAPDH and numerous other intracellular proteins convert into an insoluble disulfide-cross-linked state via the process of “nucleocytoplasmic coagulation.” Here, free radical-induced aggregation of GAPDH was studied as an in vitro model of nucleocytoplasmic coagulation. Despite the fact that disulfide cross-linking is a prominent feature of GAPDH aggregation, our data show that it is not a primary rate-determining step. To identify the true instigating event of GAPDH misfolding, we mapped the post-translational modifications that arise during its aggregation. Solvent accessibility and energy calculations of the mapped modifications within the context of the high resolution native GAPDH structure suggested that oxidation of methionine 46 may instigate aggregation. We confirmed this by mutating methionine 46 to leucine, which rendered GAPDH highly resistant to free radical-induced aggregation. Molecular dynamics simulations suggest that oxidation of methionine 46 triggers a local increase in the conformational plasticity of GAPDH that likely promotes further oxidation and eventual aggregation. Hence, methionine 46 represents a “linchpin” whereby its oxidation is a primary event permissive for the subsequent misfolding, aggregation, and disulfide cross-linking of GAPDH. A critical role for linchpin residues in nucleocytoplasmic coagulation and other forms of free radical-induced protein misfolding should now be investigated. Furthermore, because disulfide-cross-linked aggregates of GAPDH arise in many disorders and because methionine 46 is irrelevant to native GAPDH function, mutation of methionine 46 in models of disease should allow the unequivocal assessment of whether GAPDH aggregation influences disease progression. PMID:25086035

  11. Analysis of Proteins, Protein Complexes, and Organellar Proteomes Using Sheathless Capillary Zone Electrophoresis - Native Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Belov, Arseniy M.; Viner, Rosa; Santos, Marcia R.; Horn, David M.; Bern, Marshall; Karger, Barry L.; Ivanov, Alexander R.

    2017-12-01

    Native mass spectrometry (MS) is a rapidly advancing field in the analysis of proteins, protein complexes, and macromolecular species of various types. The majority of native MS experiments reported to-date has been conducted using direct infusion of purified analytes into a mass spectrometer. In this study, capillary zone electrophoresis (CZE) was coupled online to Orbitrap mass spectrometers using a commercial sheathless interface to enable high-performance separation, identification, and structural characterization of limited amounts of purified proteins and protein complexes, the latter with preserved non-covalent associations under native conditions. The performance of both bare-fused silica and polyacrylamide-coated capillaries was assessed using mixtures of protein standards known to form non-covalent protein-protein and protein-ligand complexes. High-efficiency separation of native complexes is demonstrated using both capillary types, while the polyacrylamide neutral-coated capillary showed better reproducibility and higher efficiency for more complex samples. The platform was then evaluated for the determination of monoclonal antibody aggregation and for analysis of proteomes of limited complexity using a ribosomal isolate from E. coli. Native CZE-MS, using accurate single stage and tandem-MS measurements, enabled identification of proteoforms and non-covalent complexes at femtomole levels. This study demonstrates that native CZE-MS can serve as an orthogonal and complementary technique to conventional native MS methodologies with the advantages of low sample consumption, minimal sample processing and losses, and high throughput and sensitivity. This study presents a novel platform for analysis of ribosomes and other macromolecular complexes and organelles, with the potential for discovery of novel structural features defining cellular phenotypes (e.g., specialized ribosomes). [Figure not available: see fulltext.

  12. Whole-organ re-engineering: a regenerative medicine approach to digestive organ replacement.

    PubMed

    Yagi, Hiroshi; Soto-Gutierrez, Alejandro; Kitagawa, Yuko

    2013-06-01

    Recovery from end-stage organ failure presents a challenge for the medical community, considering the limitations of extracorporeal assist devices and the shortage of donors when organ replacement is needed. There is a need for new methods to promote recovery from organ failure and regenerative medicine is an option that should be considered. Recent progress in the field of tissue engineering has opened avenues for potential clinical applications, including the use of microfluidic devices for diagnostic purposes, and bioreactors or cell/tissue-based therapies for transplantation. Early attempts to engineer tissues produced thin, planar constructs; however, recent approaches using synthetic scaffolds and decellularized tissue have achieved a more complex level of tissue organization in organs such as the urinary bladder and trachea, with some success in clinical trials. In this context, the concept of decellularization technology has been applied to produce whole organ-derived scaffolds by removing cellular content while retaining all the necessary vascular and structural cues of the native organ. In this review, we focus on organ decellularization as a new regenerative medicine approach for whole organs, which may be applied in the field of digestive surgery.

  13. Calcium dependent current recordings in Xenopus laevis oocytes in microgravity

    NASA Astrophysics Data System (ADS)

    Wuest, Simon L.; Roesch, Christian; Ille, Fabian; Egli, Marcel

    2017-12-01

    Mechanical unloading by microgravity (or weightlessness) conditions triggers profound adaptation processes at the cellular and organ levels. Among other mechanisms, mechanosensitive ion channels are thought to play a key role in allowing cells to transduce mechanical forces. Previous experiments performed under microgravity have shown that gravity affects the gating properties of ion channels. Here, a method is described to record a calcium-dependent current in native Xenopus laevis oocytes under microgravity conditions during a parabolic flight. A 3-voltage-step protocol was applied to provoke a calcium-dependent current. This current increased with extracellular calcium concentration and could be reduced by applying extracellular gadolinium. The custom-made ;OoClamp; hardware was validated by comparing the results of the 3-voltage-step protocol to results obtained with a well-established two-electrode voltage clamp (TEVC). In the context of the 2nd Swiss Parabolic Flight Campaign, we tested the OoClamp and the method. The setup and experiment protocol worked well in parabolic flight. A tendency that the calcium-dependent current was smaller under microgravity than under 1 g condition could be observed. However, a conclusive statement was not possible due to the small size of the data base that could be gathered.

  14. ELM: the status of the 2010 eukaryotic linear motif resource

    PubMed Central

    Gould, Cathryn M.; Diella, Francesca; Via, Allegra; Puntervoll, Pål; Gemünd, Christine; Chabanis-Davidson, Sophie; Michael, Sushama; Sayadi, Ahmed; Bryne, Jan Christian; Chica, Claudia; Seiler, Markus; Davey, Norman E.; Haslam, Niall; Weatheritt, Robert J.; Budd, Aidan; Hughes, Tim; Paś, Jakub; Rychlewski, Leszek; Travé, Gilles; Aasland, Rein; Helmer-Citterich, Manuela; Linding, Rune; Gibson, Toby J.

    2010-01-01

    Linear motifs are short segments of multidomain proteins that provide regulatory functions independently of protein tertiary structure. Much of intracellular signalling passes through protein modifications at linear motifs. Many thousands of linear motif instances, most notably phosphorylation sites, have now been reported. Although clearly very abundant, linear motifs are difficult to predict de novo in protein sequences due to the difficulty of obtaining robust statistical assessments. The ELM resource at http://elm.eu.org/ provides an expanding knowledge base, currently covering 146 known motifs, with annotation that includes >1300 experimentally reported instances. ELM is also an exploratory tool for suggesting new candidates of known linear motifs in proteins of interest. Information about protein domains, protein structure and native disorder, cellular and taxonomic contexts is used to reduce or deprecate false positive matches. Results are graphically displayed in a ‘Bar Code’ format, which also displays known instances from homologous proteins through a novel ‘Instance Mapper’ protocol based on PHI-BLAST. ELM server output provides links to the ELM annotation as well as to a number of remote resources. Using the links, researchers can explore the motifs, proteins, complex structures and associated literature to evaluate whether candidate motifs might be worth experimental investigation. PMID:19920119

  15. Native Hydrophobic Binding Interactions at the Transition State for Association between the TAZ1 Domain of CBP and the Disordered TAD-STAT2 Are Not a Requirement.

    PubMed

    Lindström, Ida; Dogan, Jakob

    2017-08-15

    A significant fraction of the eukaryotic proteome consists of proteins that are either partially or completely disordered under native-like conditions. Intrinsically disordered proteins (IDPs) are common in protein-protein interactions and are involved in numerous cellular processes. Although many proteins have been identified as disordered, much less is known about the binding mechanisms of the coupled binding and folding reactions involving IDPs. Here we have analyzed the rate-limiting transition state for binding between the TAZ1 domain of CREB binding protein and the intrinsically disordered transactivation domain of STAT2 (TAD-STAT2) by site-directed mutagenesis and kinetic experiments (Φ-value analysis) and found that the native protein-protein binding interface is not formed at the transition state for binding. Instead, native hydrophobic binding interactions form late, after the rate-limiting barrier has been crossed. The association rate constant in the absence of electrostatic enhancement was determined to be rather high. This is consistent with the Φ-value analysis, which showed that there are few or no obligatory native contacts. Also, linear free energy relationships clearly demonstrate that native interactions are cooperatively formed, a scenario that has usually been observed for proteins that fold according to the so-called nucleation-condensation mechanism. Thus, native hydrophobic binding interactions at the rate-limiting transition state for association between TAD-STAT2 and TAZ1 are not a requirement, which is generally in agreement with previous findings on other IDP systems and might be a common mechanism for IDPs.

  16. Nonnative Speakers' Perceptions of English "Nonlexical" Intonation Signals.

    ERIC Educational Resources Information Center

    Luthy, Melvin J.

    1983-01-01

    Native English speakers' and foreign students' perceptions of 14 English intonation signals, recorded free of verbal context, show foreign students may be misinterpreting or missing much information communicated with nonlexical signals. (Author/MSE)

  17. Contested Domains of Science and Science Learning in Contemporary Native American Communities: Three Case Studies from a National Science Foundation grant titled, "Archaeology Pathways for Native Learners"

    NASA Astrophysics Data System (ADS)

    Parent, Nancy Brossard

    This dissertation provides a critical analysis of three informal science education partnerships that resulted from a 2003-2006 National Science Foundation grant titled, "Archaeology Pathways for Native Learners" (ESI-0307858), hosted by the Mashantucket Pequot Museum and Research Center. This dissertation is designed to contribute to understandings of learning processes that occur within and at the intersection of diverse worldviews and knowledge systems, by drawing upon experiences derived from three disparate contexts: 1) The Navajo Nation Museum in Window Rock, Arizona; 2) The A:shiwi A:wan Museum and Heritage Center on the Zuni Reservation in Zuni, New Mexico; and 3) Science learning camps at the Mashantucket Pequot Museum and Research Center for Native youth of southern New England. While informal science education is increasingly moving toward decolonizing and cross-cutting institutional boundaries of learning through critical thinking and real-world applications, the construction of "science" (even within diverse contexts) continues to be framed within a homogenous, predominantly Euro-American perspective. This study analyzes the language of Western science employed in these partnerships, with particular attention to the use of Western/Native binaries that shape perceptions of Native peoples and communities, real or imagined. Connections are drawn to broader nation-state interests in education, science, and the global economy. The role of educational evaluation in these case studies is also critically analyzed, by questioning the ways in which it is constructed, conducted, and evaluated for the purposes of informing future projects and subsequent funding. This study unpacks problems of the dominant language of "expert" knowledge embedded in Western science discourse, and highlights the possibilities of indigenous knowledge systems that can inform Western science frameworks of education and evaluation. Ultimately, this study suggests that research methodologies and epistemologies that acknowledge and integrate indigenous ways of knowing can advance and broaden Western constructions of science, the academy, and educational research and praxis on a national and global scale.

  18. Why do people use exotic plants in their local medical systems? A systematic review based on Brazilian local communities

    PubMed Central

    Ferreira Júnior, Washington Soares; Ramos, Marcelo Alves; da Silva, Taline Cristina; Ladio, Ana Haydée; Albuquerque, Ulysses Paulino

    2017-01-01

    Efforts have been made to understand the processes that lead to the introduction of exotic species into local pharmacopoeias. Among those efforts, the diversification hypothesis predicts that exotic plants are introduced in local medical systems to amplify the repertoire of knowledge related to the treatment of diseases, filling blanks that were not occupied by native species. Based on such hypothesis, this study aimed to contribute to this discussion using the context of local Brazilian populations. We performed a systematic review of Brazilian studies up to 2011 involving medicinal plants, excluding those studies that presented a high risk of bias (because of sampling or plant identification problems). An analysis of similarities (ANOSIM) was conducted in different scales to test for differences in the repertoire of therapeutic indications treated using native and exotic species. We have found that although there is some overlap between native and exotic plants regarding their therapeutic indications and the body systems (BSs) that they treat, there are clear gaps present, that is, there are therapeutic indications and BSs treated that are exclusive to exotic species. This scenario enables the postulation of two alternative unfoldings of the diversification hypothesis, namely, (1) exotic species are initially introduced to fill gaps and undergo subsequent expansion of their use for medical purposes already addressed using native species and (2) exotic species are initially introduced to address problems already addressed using native species to diversify the repertoire of medicinal plants and to increase the resilience of medical systems. The reasons why exotic species may have a competitive advantage over the native ones, the implications of the introduction of exotic species for the resilience of medical systems, and the contexts in which autochthonous plants can gain strength to remain in pharmacopoeias are also discussed. PMID:28953960

  19. Asymmetric mutations in the tetrameric R67 dihydrofolate reductase reveal high tolerance to active-site substitutions.

    PubMed

    Ebert, Maximilian C C J C; Morley, Krista L; Volpato, Jordan P; Schmitzer, Andreea R; Pelletier, Joelle N

    2015-04-01

    Type II R67 dihydrofolate reductase (DHFR) is a bacterial plasmid-encoded enzyme that is intrinsically resistant to the widely-administered antibiotic trimethoprim. R67 DHFR is genetically and structurally unrelated to E. coli chromosomal DHFR and has an unusual architecture, in that four identical protomers form a single symmetrical active site tunnel that allows only one substrate binding/catalytic event at any given time. As a result, substitution of an active-site residue has as many as four distinct consequences on catalysis, constituting an atypical model of enzyme evolution. Although we previously demonstrated that no single residue of the native active site is indispensable for function, library selection here revealed a strong bias toward maintenance of two native protomers per mutated tetramer. A variety of such "half-native" tetramers were shown to procure native-like catalytic activity, with similar KM values but kcat values 5- to 33-fold lower, illustrating a high tolerance for active-site substitutions. The selected variants showed a reduced thermal stability (Tm ∼12°C lower), which appears to result from looser association of the protomers, but generally showed a marked increase in resilience to heat denaturation, recovering activity to a significantly greater extent than the variant with no active-site substitutions. Our results suggest that the presence of two native protomers in the R67 DHFR tetramer is sufficient to provide native-like catalytic rate and thus ensure cellular proliferation. © 2014 The Protein Society.

  20. Constraints on Negative Prefixation in Polish Sign Language.

    PubMed

    Tomaszewski, Piotr

    2015-01-01

    The aim of this article is to describe a negative prefix, NEG-, in Polish Sign Language (PJM) which appears to be indigenous to the language. This is of interest given the relative rarity of prefixes in sign languages. Prefixed PJM signs were analyzed on the basis of both a corpus of texts signed by 15 deaf PJM users who are either native or near-native signers, and material including a specified range of prefixed signs as demonstrated by native signers in dictionary form (i.e. signs produced in isolation, not as part of phrases or sentences). In order to define the morphological rules behind prefixation on both the phonological and morphological levels, native PJM users were consulted for their expertise. The research results can enrich models for describing processes of grammaticalization in the context of the visual-gestural modality that forms the basis for sign language structure.

  1. The Physical-Digital Divide: Exploring the Social Gap Between Digital Natives and Physical Natives.

    PubMed

    Ball, Christopher; Francis, Jessica; Huang, Kuo-Ting; Kadylak, Travis; Cotten, Shelia R; Rikard, R V

    2017-09-01

    Older adults are the most digitally divided demographic group. The present study explores how older adults perceive the physical use of information and communication technologies (ICTs), particularly across generations and contexts. Data for the present study come from nine focus groups. Seniors acknowledge that ICTs help them connect with geographically distant social ties, but that they lead to feelings of disconnection with geographically close social ties. We label this phenomenon the "physical-digital divide," which exists when a group feels ostracized or offended when those around them engage with ICTs while they themselves are not or cannot engage with ICTs. Younger generations are often referred to as "digital natives" and older generations as "digital immigrants." A more apt label for older adults may be "physical natives," as their preferred method of communication involves physical face-to-face interactions and traditional codes of etiquette. Suggestions are made for reducing the physical-digital divide.

  2. Environment and Urban Tourism: AN Emergent System in Rhetorical Place Identity Definitions

    NASA Astrophysics Data System (ADS)

    Mura, Marina

    Within the systemic framework of Environmental Psychology (Bechtel and Churchman, 2002) and following Urry (2002) and Pearce's approaches (2005), the aim of this research is to investigate within the context of urban tourism which world views emerge from a Discourse Analysis (Edwards, Potter, 1993). of the speech of native and non-native Sardinian residents. It addresses the issue of how social-physical diversity might be preserved (the problem of tourism sustainability, Di Castri, Balaji, 2002). In this regard, forty in-depth narrative interviews of inhabitants with short- and long-term residential experience in Cagliari (Italy) were conducted and examined (Discourse Analysis). It was found that the native and non-native's rhetorical devices expressed similar representations of urban places, but in diverse relationship to social and place identity. Their environmental transitions were based on the tourist gaze, or the functional view and heritage pride. This displays some basic central dimensions of sustainable tourism.

  3. Creating Age Asymmetry: Consequences of Inheriting Damaged Goods in Mammalian Cells.

    PubMed

    Moore, Darcie L; Jessberger, Sebastian

    2017-01-01

    Accumulating evidence suggests that mammalian cells asymmetrically segregate cellular components ranging from genomic DNA to organelles and damaged proteins during cell division. Asymmetric inheritance upon mammalian cell division may be specifically important to ensure cellular fitness and propagate cellular potency to individual progeny, for example in the context of somatic stem cell division. We review here recent advances in the field and discuss potential effects and underlying mechanisms that mediate asymmetric segregation of cellular components during mammalian cell division. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Revisiting Robinson: The perils of individualistic and ecologic fallacy

    PubMed Central

    Subramanian, S V; Jones, Kelvyn; Kaddour, Afamia; Krieger, Nancy

    2009-01-01

    Background W S Robinson made a seminal contribution by demonstrating that correlations for the same two variables can be different at the individual and ecologic level. This study reanalyzes and historically situates Robinson's influential study that laid the foundation for the primacy of analyzing data at only the individual level. Methods We applied a binomial multilevel logistic model to analyse variation in illiteracy as enumerated by the 1930 US. Census (the same data as used by Robinson). The outcome was log odds of being illiterate, while predictors were race/nativity (‘native whites’, ‘foreign-born whites’ and ‘negroes’) at the individual-level, and presence of Jim Crow segregation laws for education at the state-level. We conducted historical research to identify the social and scientific context within which Robinson's study was produced and favourably received. Results Empirically, the substantial state variations in illiteracy could not be accounted by the states' race/nativity composition. Different approaches to modelling state-effects yielded considerably attenuated associations at the individual-level between illiteracy and race/nativity. Furthermore, state variation in illiteracy was different across the race/nativity groups, with state variation being largest for whites and least for foreign-born whites. Strong effects of Jim Crow education laws on illiteracy were observed with the effect being strongest for blacks. Historically, Robinson's study was consonant with the post-World War II ascendancy of methodological individualism. Conclusion Applying a historically informed multilevel perspective to Robinson's profoundly influential study, we demonstrate that meaningful analysis of individual-level relationships requires attention to substantial heterogeneity in state characteristics. The implication is that perils are posed by not only ecological fallacy but also individualistic fallacy. Multilevel thinking, grounded in historical and spatiotemporal context, is thus a necessity, not an option. PMID:19179348

  5. Revisiting Robinson: the perils of individualistic and ecologic fallacy.

    PubMed

    Subramanian, S V; Jones, Kelvyn; Kaddour, Afamia; Krieger, Nancy

    2009-04-01

    W S Robinson made a seminal contribution by demonstrating that correlations for the same two variables can be different at the individual and ecologic level. This study reanalyzes and historically situates Robinson's influential study that laid the foundation for the primacy of analyzing data at only the individual level. We applied a binomial multilevel logistic model to analyse variation in illiteracy as enumerated by the 1930 US. Census (the same data as used by Robinson). The outcome was log odds of being illiterate, while predictors were race/nativity ('native whites', 'foreign-born whites' and 'negroes') at the individual-level, and presence of Jim Crow segregation laws for education at the state-level. We conducted historical research to identify the social and scientific context within which Robinson's study was produced and favourably received. Empirically, the substantial state variations in illiteracy could not be accounted by the states' race/nativity composition. Different approaches to modelling state-effects yielded considerably attenuated associations at the individual-level between illiteracy and race/nativity. Furthermore, state variation in illiteracy was different across the race/nativity groups, with state variation being largest for whites and least for foreign-born whites. Strong effects of Jim Crow education laws on illiteracy were observed with the effect being strongest for blacks. Historically, Robinson's study was consonant with the post-World War II ascendancy of methodological individualism. Applying a historically informed multilevel perspective to Robinson's profoundly influential study, we demonstrate that meaningful analysis of individual-level relationships requires attention to substantial heterogeneity in state characteristics. The implication is that perils are posed by not only ecological fallacy but also individualistic fallacy. Multilevel thinking, grounded in historical and spatiotemporal context, is thus a necessity, not an option.

  6. Pre-Columbian floristic legacies in modern homegardens of Central Amazonia.

    PubMed

    Lins, Juliana; Lima, Helena P; Baccaro, Fabricio B; Kinupp, Valdely F; Shepard, Glenn H; Clement, Charles R

    2015-01-01

    Historical ecologists have demonstrated legacy effects in apparently wild landscapes in Europe, North America, Mesoamerica, Amazonia, Africa and Oceania. People live and farm in archaeological sites today in many parts of the world, but nobody has looked for the legacies of past human occupations in the most dynamic areas in these sites: homegardens. Here we show that the useful flora of modern homegardens is partially a legacy of pre-Columbian occupations in Central Amazonia: the more complex the archaeological context, the more variable the floristic composition of useful native plants in homegardens cultivated there today. Species diversity was 10% higher in homegardens situated in multi-occupational archaeological contexts compared with homegardens situated in single-occupational ones. Species heterogeneity (β-diversity) among archaeological contexts was similar for the whole set of species, but markedly different when only native Amazonian species were included, suggesting the influence of pre-conquest indigenous occupations on current homegarden species composition. Our findings show that the legacy of pre-Columbian occupations is visible in the most dynamic of all agroecosystems, adding another dimension to the human footprint in the Amazonian landscape.

  7. The Safety Dance: Biophysics of Membrane Protein Folding and Misfolding in a Cellular Context

    PubMed Central

    Schlebach, Jonathan P.; Sanders, Charles R.

    2015-01-01

    Most biological processes require the production and degradation of proteins, a task that weighs heavily on the cell. Mutations that compromise the conformational stability of proteins place both specific and general burdens on cellular protein homeostasis (proteostasis) in ways that contribute to numerous diseases. Efforts to elucidate the chain of molecular events responsible for diseases of protein folding address one of the foremost challenges in biomedical science. However, relatively little is known about the processes by which mutations prompt the misfolding of α-helical membrane proteins, which rely on an intricate network of cellular machinery to acquire and maintain their functional structures within cellular membranes. In this review, we summarize the current understanding of the physical principles that guide membrane protein biogenesis and folding in the context of mammalian cells. Additionally, we explore how pathogenic mutations that influence biogenesis may differ from those that disrupt folding and assembly, as well as how this may relate to disease mechanisms and therapeutic intervention. These perspectives indicate an imperative for the use of information from structural, cellular, and biochemical studies of membrane proteins in the design of novel therapeutics and in personalized medicine. PMID:25420508

  8. Effect of Vowel Context on the Recognition of Initial Consonants in Kannada.

    PubMed

    Kalaiah, Mohan Kumar; Bhat, Jayashree S

    2017-09-01

    The present study was carried out to investigate the effect of vowel context on the recognition of Kannada consonants in quiet for young adults. A total of 17 young adults with normal hearing in both ears participated in the study. The stimuli included consonant-vowel syllables, spoken by 12 native speakers of Kannada. Consonant recognition task was carried out as a closed-set (fourteen-alternative forced-choice). The present study showed an effect of vowel context on the perception of consonants. Maximum consonant recognition score was obtained in the /o/ vowel context, followed by the /a/ and /u/ vowel contexts, and then the /e/ context. Poorest consonant recognition score was obtained in the vowel context /i/. Vowel context has an effect on the recognition of Kannada consonants, and the vowel effect was unique for Kannada consonants.

  9. The introduced tree Prosopis juliflora is a serious threat to native species of the Brazilian Caatinga vegetation.

    PubMed

    de Souza Nascimento, Clóvis Eduardo; Tabarelli, Marcelo; da Silva, Carlos Alberto Domingues; Leal, Inara Roberta; de Souza Tavares, Wagner; Serrão, José Eduardo; Zanuncio, José Cola

    2014-05-15

    Despite its economic importance in the rural context, the Prosopis juliflora tree species has already invaded millions of hectares globally (particularly rangelands), threatening native biodiversity and rural sustainability. Here we examine seedling growth (leaf area, stem diameter, plant height) and seedling mortality across five native plant species of the Caatinga vegetation in response to competition with P. juliflora. Two sowing treatments with 10 replications were adopted within a factorial 2 × 5 randomized block design. Treatments consisted of P. juliflora seeds sowed with seeds of Caesalpinia ferrea, Caesalpinia microphylla, Erythrina velutina, Mimosa bimucronata and Mimosa tenuiflora (one single native species per treatment), while seeds of native species sowed without P. juliflora were adopted as controls. Overall, our results suggest that P. juliflora can reduce seedling growth by half and cause increased seedling mortality among woody plant species. Moreover, native species exhibit different levels of susceptibility to competition with P. juliflora, particularly in terms of plant growth. Such a superior competitive ability apparently permits P. juliflora to establish monospecific stands of adult trees, locally displacing native species or limiting their recruitment. The use of less sensitive species, such as C. ferrea and M. tenuiflora, to restore native vegetation before intensive colonization by P. juliflora should be investigated as an effective approach for avoiding its continuous spread across the Caatinga region. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Context Specificity of Stress-activated Mitogen-activated Protein (MAP) Kinase Signaling: The Story as Told by Caenorhabditis elegans*

    PubMed Central

    Andrusiak, Matthew G.; Jin, Yishi

    2016-01-01

    Stress-associated p38 and JNK mitogen-activated protein (MAP) kinase signaling cascades trigger specific cellular responses and are involved in multiple disease states. At the root of MAP kinase signaling complexity is the differential use of common components on a context-specific basis. The roundworm Caenorhabditis elegans was developed as a system to study genes required for development and nervous system function. The powerful genetics of C. elegans in combination with molecular and cellular dissections has led to a greater understanding of how p38 and JNK signaling affects many biological processes under normal and stress conditions. This review focuses on the studies revealing context specificity of different stress-activated MAPK components in C. elegans. PMID:26907690

  11. Prevalence and multiplicity of cutaneous beta papilloma viruses in plucked hairs depend on cellular DNA input.

    PubMed

    Weissenborn, S J; Neale, R; de Koning, M N C; Waterboer, T; Abeni, D; Bouwes Bavinck, J N; Wieland, U; Pfister, H J

    2009-11-01

    In view of the low loads of beta human papillomaviruses in skin samples, amounts of cellular DNA used in qualitative PCR may become limiting for virus detection and introduce variations in prevalence and multiplicity. This issue was explored within the context of a multicentre study and increasing prevalence and multiplicity was found with increasing input amounts of cellular DNA extracted from hair bulbs. To improve the quality and comparability between different epidemiologic studies ideally equal amounts of cellular DNA should be employed. When cellular DNA input varies this should be clearly taken into account in assessing viral prevalence and multiplicity.

  12. Exploring public perception of non-native species from a visions of nature perspective.

    PubMed

    Verbrugge, Laura N H; Van den Born, Riyan J G; Lenders, H J Rob

    2013-12-01

    Not much is known about lay public perceptions of non-native species and their underlying values. Public awareness and engagement, however, are important aspects in invasive species management. In this study, we examined the relations between the lay public's visions of nature, their knowledge about non-native species, and their perceptions of non-native species and invasive species management with a survey administered in the Netherlands. Within this framework, we identified three measures for perception of non-native species: perceived risk, control and engagement. In general, respondents scored moderate values for perceived risk and personal engagement. However, in case of potential ecological or human health risks, control measures were supported. Respondents' images of the human-nature relationship proved to be relevant in engagement in problems caused by invasive species and in recognizing the need for control, while images of nature appeared to be most important in perceiving risks to the environment. We also found that eradication of non-native species was predominantly opposed for species with a high cuddliness factor such as mammals and bird species. We conclude that lay public perceptions of non-native species have to be put in a wider context of visions of nature, and we discuss the implications for public support for invasive species management.

  13. Minimal Effects of an Invasive Flowering Shrub on the Pollinator Community of Native Forbs

    PubMed Central

    Chung, Y. Anny; Burkle, Laura A.; Knight, Tiffany M.

    2014-01-01

    Biological invasions can strongly influence species interactions such as pollination. Most of the documented effects of exotic plant species on plant-pollinator interactions have been observational studies using single pairs of native and exotic plants, and have focused on dominant exotic plant species. We know little about how exotic plants alter interactions in entire communities of plants and pollinators, especially at low to medium invader densities. In this study, we began to address these gaps by experimentally removing the flowers of a showy invasive shrub, Rosa multiflora, and evaluating its effects on the frequency, richness, and composition of bee visitors to co-flowering native plants. We found that while R. multiflora increased plot-level richness of bee visitors to co-flowering native plant species at some sites, its presence had no significant effects on bee visitation rate, visitor richness, bee community composition, or abundance overall. In addition, we found that compared to co-flowering natives, R. multiflora was a generalist plant that primarily received visits from generalist bee species shared with native plant species. Our results suggest that exotic plants such as R. multiflora may facilitate native plant pollination in a community context by attracting a more diverse assemblage of pollinators, but have limited and idiosyncratic effects on the resident plant-pollinator network in general. PMID:25343718

  14. Endothelial Progenitor Cells as a Sole Source for Ex Vivo Seeding of Tissue-Engineered Heart Valves

    PubMed Central

    Mettler, Bret A.; Engelmayr, George C.; Aikawa, Elena; Bischoff, Joyce; Martin, David P.; Exarhopoulos, Alexis; Moses, Marsha A.; Schoen, Frederick J.; Sacks, Michael S.

    2010-01-01

    Purposes: We investigated whether circulating endothelial progenitor cells (EPCs) can be used as a cell source for the creation of a tissue-engineered heart valve (TEHV). Methods: Trileaflet valved conduits were fabricated using nonwoven polyglycolic acid/poly-4-hydroxybutyrate polymer. Ovine peripheral blood EPCs were dynamically seeded onto a valved conduit and incubated for 7, 14, and 21 days. Results: Before seeding, EPCs were shown to express CD31+, eNOS+, and VE-Cadherin+ but not α-smooth muscle actin. Histological analysis demonstrated relatively homogenous cellular ingrowth throughout the valved conduit. TEHV constructs revealed the presence of endothelial cell (EC) markers and α-smooth muscle actin+ cells comparable with native valves. Protein levels were comparable with native valves and exceeded those in unseeded controls. EPC-TEHV demonstrated a temporal pattern of matrix metalloproteinases-2/9 expression and tissue inhibitors of metalloproteinase activities comparable to that of native valves. Mechanical properties of EPC-TEHV demonstrated significantly greater stiffness than that of the unseeded scaffolds and native valves. Conclusions: Circulating EPC appears to have the potential to provide both interstitial and endothelial functions and could potentially serve as a single-cell source for construction of autologous heart valves. PMID:19698056

  15. Biomolecular interactions modulate macromolecular structure and dynamics in atomistic model of a bacterial cytoplasm.

    PubMed

    Yu, Isseki; Mori, Takaharu; Ando, Tadashi; Harada, Ryuhei; Jung, Jaewoon; Sugita, Yuji; Feig, Michael

    2016-11-01

    Biological macromolecules function in highly crowded cellular environments. The structure and dynamics of proteins and nucleic acids are well characterized in vitro, but in vivo crowding effects remain unclear. Using molecular dynamics simulations of a comprehensive atomistic model cytoplasm we found that protein-protein interactions may destabilize native protein structures, whereas metabolite interactions may induce more compact states due to electrostatic screening. Protein-protein interactions also resulted in significant variations in reduced macromolecular diffusion under crowded conditions, while metabolites exhibited significant two-dimensional surface diffusion and altered protein-ligand binding that may reduce the effective concentration of metabolites and ligands in vivo. Metabolic enzymes showed weak non-specific association in cellular environments attributed to solvation and entropic effects. These effects are expected to have broad implications for the in vivo functioning of biomolecules. This work is a first step towards physically realistic in silico whole-cell models that connect molecular with cellular biology.

  16. Role of naturally occurring osmolytes in protein folding and stability.

    PubMed

    Kumar, Raj

    2009-11-01

    Osmolytes are typically accumulated in the intracellular environment at relatively high concentrations when cells/tissues are subjected to stress conditions. Osmolytes are common in a variety of organisms, including microorganisms, plants, and animals. They enhance thermodynamic stability of proteins by providing natively folded conformations without perturbing other cellular processes. By burying the backbone into the core of folded proteins, osmolytes can provide significant stability to proteins. Two properties of osmolytes are particularly important: (i) their ability to impart increased thermodynamic stability to folded proteins; and (ii) their compatibility in the intracellular environment at high concentrations. Under physiological conditions, the cellular compositions of osmolytes may vary significantly. This may lead to different protein folding pathways utilized in cells depending upon the intracellular environment. Proper understanding of the role of osmolytes in cell regulation should allow predicting the action of osmolytes on macromolecular interactions in stressed and crowded environments typical of cellular conditions.

  17. Effect of processing on physicochemical characteristics and bioefficacy of β-lactoglobulin-epigallocatechin-3-gallate complexes.

    PubMed

    Lestringant, Pauline; Guri, Anilda; Gülseren, Ibrahim; Relkin, Perla; Corredig, Milena

    2014-08-20

    Varying amounts of epigallocatechin-3-gallate (EGCG) were encapsulated in β-lactoglobulin (β-Lg) nanoparticles, either native or processed, denoted as heated or desolvated protein. The stability, physical properties, and bioactivity of the β-Lg-EGCG complexes were tested. Native β-Lg-EGCG complexes showed comparable stability and binding efficacy (EGCG/β-Lg molar ratio of 1:1) to heated β-Lg nanoparticles (1% and 5% protein w/w). The sizes of heated and desolvated β-Lg nanoparticles were comparable, but the latter showed the highest binding affinity for EGCG. The presence of EGCG complexed with β-Lg did not affect the interfacial tension of the protein when tested at the soy oil-water interface but caused a decrease in dilational elasticity. All β-Lg complexes (native, heated, or desolvated) showed a decrease in cellular proliferation similar to that of free ECGC. In summary, protein-EGCG complexes did not alter the bioefficacy of EGCG and contributed to increased stability with storage, demonstrating the potential benefits of nanoencapsulation.

  18. Engineering hydrogels as extracellular matrix mimics

    PubMed Central

    Geckil, Hikmet; Xu, Feng; Zhang, Xiaohui; Moon, SangJun

    2010-01-01

    Extracellular matrix (ECM) is a complex cellular environment consisting of proteins, proteoglycans, and other soluble molecules. ECM provides structural support to mammalian cells and a regulatory milieu with a variety of important cell functions, including assembling cells into various tissues and organs, regulating growth and cell–cell communication. Developing a tailored in vitro cell culture environment that mimics the intricate and organized nanoscale meshwork of native ECM is desirable. Recent studies have shown the potential of hydrogels to mimic native ECM. Such an engineered native-like ECM is more likely to provide cells with rational cues for diagnostic and therapeutic studies. The research for novel biomaterials has led to an extension of the scope and techniques used to fabricate biomimetic hydrogel scaffolds for tissue engineering and regenerative medicine applications. In this article, we detail the progress of the current state-of-the-art engineering methods to create cell-encapsulating hydrogel tissue constructs as well as their applications in in vitro models in biomedicine. PMID:20394538

  19. Clonal dynamics of native haematopoiesis

    PubMed Central

    Sun, Jianlong; Ramos, Azucena; Chapman, Brad; Johnnidis, Jonathan B.; Le, Linda; Ho, Yu-Jui; Klein, Allon; Hofmann, Oliver; Camargo, Fernando D.

    2015-01-01

    It is currently thought that life-long blood cell production is driven by the action of a small number of multipotent haematopoietic stem cells. Evidence supporting this view has been largely acquired through the use of functional assays involving transplantation. However, whether these mechanisms also govern native non-transplant haematopoiesis is entirely unclear. Here we have established a novel experimental model in mice where cells can be uniquely and genetically labelled in situ to address this question. Using this approach, we have performed longitudinal analyses of clonal dynamics in adult mice that reveal unprecedented features of native haematopoiesis. In contrast to what occurs following transplantation, steady-state blood production is maintained by the successive recruitment of thousands of clones, each with a minimal contribution to mature progeny. Our results demonstrate that a large number of long-lived progenitors, rather than classically defined haematopoietic stem cells, are the main drivers of steady-state haematopoiesis during most of adulthood. Our results also have implications for understanding the cellular origin of haematopoietic disease. PMID:25296256

  20. Clonal dynamics of native haematopoiesis.

    PubMed

    Sun, Jianlong; Ramos, Azucena; Chapman, Brad; Johnnidis, Jonathan B; Le, Linda; Ho, Yu-Jui; Klein, Allon; Hofmann, Oliver; Camargo, Fernando D

    2014-10-16

    It is currently thought that life-long blood cell production is driven by the action of a small number of multipotent haematopoietic stem cells. Evidence supporting this view has been largely acquired through the use of functional assays involving transplantation. However, whether these mechanisms also govern native non-transplant haematopoiesis is entirely unclear. Here we have established a novel experimental model in mice where cells can be uniquely and genetically labelled in situ to address this question. Using this approach, we have performed longitudinal analyses of clonal dynamics in adult mice that reveal unprecedented features of native haematopoiesis. In contrast to what occurs following transplantation, steady-state blood production is maintained by the successive recruitment of thousands of clones, each with a minimal contribution to mature progeny. Our results demonstrate that a large number of long-lived progenitors, rather than classically defined haematopoietic stem cells, are the main drivers of steady-state haematopoiesis during most of adulthood. Our results also have implications for understanding the cellular origin of haematopoietic disease.

  1. The molten globule state is unusually deformable under mechanical force

    PubMed Central

    Elms, Phillip J.; Chodera, John D.; Bustamante, Carlos; Marqusee, Susan

    2012-01-01

    Recently, the role of force in cellular processes has become more evident, and now with advances in force spectroscopy, the response of proteins to force can be directly studied. Such studies have found that native proteins are brittle, and thus not very deformable. Here, we examine the mechanical properties of a class of intermediates referred to as the molten globule state. Using optical trap force spectroscopy, we investigated the response to force of the native and molten globule states of apomyoglobin along different pulling axes. Unlike natively folded proteins, the molten globule state of apomyoglobin is compliant (large distance to the transition state); this large compliance means that the molten globule is more deformable and the unfolding rate is more sensitive to force (the application of force or tension will have a more dramatic effect on the unfolding rate). Our studies suggest that these are general properties of molten globules and could have important implications for mechanical processes in the cell. PMID:22355138

  2. Defining the impact of non-native species.

    PubMed

    Jeschke, Jonathan M; Bacher, Sven; Blackburn, Tim M; Dick, Jaimie T A; Essl, Franz; Evans, Thomas; Gaertner, Mirijam; Hulme, Philip E; Kühn, Ingolf; Mrugała, Agata; Pergl, Jan; Pyšek, Petr; Rabitsch, Wolfgang; Ricciardi, Anthony; Richardson, David M; Sendek, Agnieszka; Vilà, Montserrat; Winter, Marten; Kumschick, Sabrina

    2014-10-01

    Non-native species cause changes in the ecosystems to which they are introduced. These changes, or some of them, are usually termed impacts; they can be manifold and potentially damaging to ecosystems and biodiversity. However, the impacts of most non-native species are poorly understood, and a synthesis of available information is being hindered because authors often do not clearly define impact. We argue that explicitly defining the impact of non-native species will promote progress toward a better understanding of the implications of changes to biodiversity and ecosystems caused by non-native species; help disentangle which aspects of scientific debates about non-native species are due to disparate definitions and which represent true scientific discord; and improve communication between scientists from different research disciplines and between scientists, managers, and policy makers. For these reasons and based on examples from the literature, we devised seven key questions that fall into 4 categories: directionality, classification and measurement, ecological or socio-economic changes, and scale. These questions should help in formulating clear and practical definitions of impact to suit specific scientific, stakeholder, or legislative contexts. © 2014 The Authors. Conservation Biology published by Wiley Periodicals, Inc., on behalf of the Society for Conservation Biology.

  3. Prevalence of High-Risk Sexual Behaviors Among Monoracial and Multiracial Groups from a National Sample: Are Multiracial Young Adults at Greater Risk?

    PubMed

    Landor, Antoinette M; Halpern, Carolyn Tucker

    2016-02-01

    The present study compared the prevalence and variation in high-risk sexual behaviors among four monoracial (i.e., White, African American, Asian, Native American) and four multiracial (i.e., White/African American, White/Asian, White/Native American, African American/Native American) young adults using Wave IV data (2008-2009) from the National Longitudinal Study of Adolescent to Adult Health (N = 9724). Findings indicated differences in the sexual behavior of monoracial and multiracial young adults, but directions of differences varied depending on the monoracial group used as the referent and gender. Among males, White/African Americans had higher risk than Whites; White/Native Americans had higher risk than Native Americans. Otherwise, multiracial groups had lower risk or did not differ from the single-race groups. Among females, White/Native Americans had higher risk than Whites; White/African Americans had higher risk than African Americans. Other comparisons showed no differences or had lower risk among multiracial groups. Variations in high-risk sexual behaviors underscore the need for health research to disaggregate multiracial groups to better understand health behaviors and outcomes in the context of experiences associated with a multiracial background, and to improve prevention strategies.

  4. Implications for Language Diversity in Instruction in the Context of Target Language Classrooms: Development of a Preliminary Model of the Effectiveness of Teacher Code-Switching

    ERIC Educational Resources Information Center

    Lee, Jang Ho

    2012-01-01

    This paper concerns the conceptual and pedagogical issues that revolve around target language (TL) only instruction and teacher code-switching in the context of TL classrooms. To this end, I first examine four intertwined ideas (that is, monolingualism, naturalism, native-speakerism, and absolutism) that run through the monolingual approach to TL…

  5. Speaker-independent factors affecting the perception of foreign accent in a second languagea)

    PubMed Central

    Levi, Susannah V.; Winters, Stephen J.; Pisoni, David B.

    2012-01-01

    Previous research on foreign accent perception has largely focused on speaker-dependent factors such as age of learning and length of residence. Factors that are independent of a speaker’s language learning history have also been shown to affect perception of second language speech. The present study examined the effects of two such factors—listening context and lexical frequency—on the perception of foreign-accented speech. Listeners rated foreign accent in two listening contexts: auditory-only, where listeners only heard the target stimuli, and auditory+orthography, where listeners were presented with both an auditory signal and an orthographic display of the target word. Results revealed that higher frequency words were consistently rated as less accented than lower frequency words. The effect of the listening context emerged in two interactions: the auditory +orthography context reduced the effects of lexical frequency, but increased the perceived differences between native and non-native speakers. Acoustic measurements revealed some production differences for words of different levels of lexical frequency, though these differences could not account for all of the observed interactions from the perceptual experiment. These results suggest that factors independent of the speakers’ actual speech articulations can influence the perception of degree of foreign accent. PMID:17471745

  6. Culture, context, and the internalizing distress of Mexican American youth.

    PubMed

    Polo, Antonio J; López, Steven R

    2009-03-01

    Latino youth appear to be at higher risk for depression relative to youth from other ethnic groups. This study assessed the relationship between nativity and several forms of internalizing distress among Mexican American middle school students as well as sociocultural factors that may help explain this relationship. Immigrant Mexican American youth (n = 78) reported significantly higher social anxiety and loneliness than U.S.-born Mexican American youth (n = 83). Acculturation stress and English proficiency were identified as significant mediators of these nativity differences. Although internalizing problems and depression symptoms did not vary across nativity groups, both were related to lower affiliative obedience. The findings point to cultural socialization values and contextual influences as important variables in the mental health of youth in immigrant families.

  7. Microfluidic hydrogels for tissue engineering.

    PubMed

    Huang, Guo You; Zhou, Li Hong; Zhang, Qian Cheng; Chen, Yong Mei; Sun, Wei; Xu, Feng; Lu, Tian Jian

    2011-03-01

    With advanced properties similar to the native extracellular matrix, hydrogels have found widespread applications in tissue engineering. Hydrogel-based cellular constructs have been successfully developed to engineer different tissues such as skin, cartilage and bladder. Whilst significant advances have been made, it is still challenging to fabricate large and complex functional tissues due mainly to the limited diffusion capability of hydrogels. The integration of microfluidic networks and hydrogels can greatly enhance mass transport in hydrogels and spatiotemporally control the chemical microenvironment of cells, mimicking the function of native microvessels. In this review, we present and discuss recent advances in the fabrication of microfluidic hydrogels from the viewpoint of tissue engineering. Further development of new hydrogels and microengineering technologies will have a great impact on tissue engineering.

  8. Defining efficient enzyme-cofactor pairs for bioorthogonal profiling of protein methylation

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

    Islam, Kabirul; Chen, Yuling; Wu, Hong

    2013-11-18

    Protein methyltransferase (PMT)-mediated posttranslational modification of histone and nonhistone substrates modulates stability, localization, and interacting partners of target proteins in diverse cellular contexts. These events play critical roles in normal biological processes and are frequently deregulated in human diseases. In the course of identifying substrates of individual PMTs, bioorthogonal profiling of protein methylation (BPPM) has demonstrated its merits. In this approach, specific PMTs are engineered to process S-adenosyl-L-methionine (SAM) analogs as cofactor surrogates and label their substrates with distinct chemical modifications for target elucidation. Despite the proof-of-concept advancement of BPPM, few efforts have been made to explore its generality. Withmore » two cancer-relevant PMTs, EuHMT1 (GLP1/KMT1D) and EuHMT2 (G9a/KMT1C), as models, we defined the key structural features of engineered PMTs and matched SAM analogs that can render the orthogonal enzyme–cofactor pairs for efficient catalysis. Here we have demonstrated that the presence of sulfonium-β-sp 2 carbon and flexible, medium-sized sulfonium-δ-substituents are crucial for SAM analogs as BPPM reagents. The bulky cofactors can be accommodated by tailoring the conserved Y1211/Y1154 residues and nearby hydrophobic cavities of EuHMT1/2. Profiling proteome-wide substrates with BPPM allowed identification of >500 targets of EuHMT1/2 with representative targets validated using native EuHMT1/2 and SAM. This finding indicates that EuHMT1/2 may regulate many cellular events previously unrecognized to be modulated by methylation. The present work, therefore, paves the way to a broader application of the BPPM technology to profile methylomes of diverse PMTs and elucidate their downstream functions.« less

  9. AMERICAN INDIAN AND ALASKA NATIVE BOYS: EARLY CHILDHOOD RISK AND RESILIENCE AMIDST CONTEXT AND CULTURE.

    PubMed

    Sarche, Michelle; Tafoya, Greg; Croy, Calvin D; Hill, Kyle

    2017-01-01

    American Indian and Alaska Native (AIAN) adolescent and adult men experience a range of health disparities relative to their non-AIAN counterparts and AIAN women. Given the relatively limited literature on early development in tribal contexts, however, indicators of risk during early childhood specific to AIAN boys are not well-known. The current article reviews sources of strength and challenge within AIAN communities for AIAN children in general, including cultural beliefs and practices that support development, and contextual challenges related to socioeconomic and health disparities and historical trauma affecting the AIAN population as a whole. The research literature on early development is reviewed, highlighting what this literature reveals about early gender differences. The article concludes with calls to action on behalf of AIAN boys that align with each of the five tiers of R. Frieden's (2010) Public Health Pyramid. © 2016 Michigan Association for Infant Mental Health.

  10. Proficiency and sentence constraint effects on second language word learning.

    PubMed

    Ma, Tengfei; Chen, Baoguo; Lu, Chunming; Dunlap, Susan

    2015-07-01

    This paper presents an experiment that investigated the effects of L2 proficiency and sentence constraint on semantic processing of unknown L2 words (pseudowords). All participants were Chinese native speakers who learned English as a second language. In the experiment, we used a whole sentence presentation paradigm with a delayed semantic relatedness judgment task. Both higher and lower-proficiency L2 learners could make use of the high-constraint sentence context to judge the meaning of novel pseudowords, and higher-proficiency L2 learners outperformed lower-proficiency L2 learners in all conditions. These results demonstrate that both L2 proficiency and sentence constraint affect subsequent word learning among second language learners. We extended L2 word learning into a sentence context, replicated the sentence constraint effects previously found among native speakers, and found proficiency effects in L2 word learning. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Measurement equivalence of four psychological questionnaires in native-born Germans, Russian-speaking immigrants, and native-born Russians.

    PubMed

    Hirsch, Oliver; Donner-Banzhoff, Norbert; Bachmann, Viktoria

    2013-07-01

    Psychological constructs depend on cultural context. It is therefore important to show the equivalence of measurement instruments in cross-cultural research. There is evidence that in Russian-speaking immigrants, cultural and language issues are important in health care. We examined measurement equivalence of the Patient Health Questionnaire-9 (PHQ-9), the Patient Health Questionnaire-15 (PHQ-15), the Hamburg Self-Care Questionnaire (HamSCQ), and the questionnaire on communication preferences of patients with chronic illness (KOPRA) in native-born Germans, Russian-speaking immigrants living in Germany, and native-born Russians living in the former Soviet Union (FSU). All four questionnaires fulfilled requirements of measurement equivalence in confirmatory factor analyses and analyses of differential item functioning. The Russian translations can be used in Russian-speaking immigrants and native-born Russians. This offers further possibilities for cross-cultural research and for an improvement in health care research in Russian-speaking immigrants in Germany. The most pronounced differences occurred in the KOPRA, which point to differences in German and Russian health care systems.

  12. Distinct Cellular Locations of Carbonic Anhydrases Mediate Carbon Dioxide Control of Stomatal Movements1[OPEN

    PubMed Central

    Hu, Honghong; Rappel, Wouter-Jan; Occhipinti, Rossana; Ries, Amber; Böhmer, Maik; You, Lei; Xiao, Chuanlei; Engineer, Cawas B.; Boron, Walter F.; Schroeder, Julian I.

    2015-01-01

    Elevated carbon dioxide (CO2) in leaves closes stomatal apertures. Research has shown key functions of the β-carbonic anhydrases (βCA1 and βCA4) in rapid CO2-induced stomatal movements by catalytic transmission of the CO2 signal in guard cells. However, the underlying mechanisms remain unclear, because initial studies indicate that these Arabidopsis (Arabidopsis thaliana) βCAs are targeted to distinct intracellular compartments upon expression in tobacco (Nicotiana benthamiana) cells. Which cellular location of these enzymes plays a key role in native guard cells in CO2-regulated stomatal movements remains unknown. Here, we express fluorescently tagged CAs in guard cells of ca1ca4 double-mutant plants and show that the specific locations of βCA4 at the plasma membrane and βCA1 in native guard cell chloroplasts each can mediate rapid CO2 control of stomatal movements. Localization and complementation analyses using a mammalian αCAII-yellow fluorescent protein in guard cells further show that cytoplasmic localization is also sufficient to restore CO2 regulation of stomatal conductance. Mathematical modeling of cellular CO2 catalysis suggests that the dynamics of the intracellular HCO3− concentration change in guard cells can be driven by plasma membrane and cytoplasmic localizations of CAs but not as clearly by chloroplast targeting. Moreover, modeling supports the notion that the intracellular HCO3− concentration dynamics in guard cells are a key mechanism in mediating CO2-regulated stomatal movements but that an additional chloroplast role of CAs exists that has yet to be identified. PMID:26243620

  13. Gas Transfer in Cellularized Collagen-Membrane Gas Exchange Devices.

    PubMed

    Lo, Justin H; Bassett, Erik K; Penson, Elliot J N; Hoganson, David M; Vacanti, Joseph P

    2015-08-01

    Chronic lower respiratory disease is highly prevalent in the United States, and there remains a need for alternatives to lung transplant for patients who progress to end-stage lung disease. Portable or implantable gas oxygenators based on microfluidic technologies can address this need, provided they operate both efficiently and biocompatibly. Incorporating biomimetic materials into such devices can help replicate native gas exchange function and additionally support cellular components. In this work, we have developed microfluidic devices that enable blood gas exchange across ultra-thin collagen membranes (as thin as 2 μm). Endothelial, stromal, and parenchymal cells readily adhere to these membranes, and long-term culture with cellular components results in remodeling, reflected by reduced membrane thickness. Functionally, acellular collagen-membrane lung devices can mediate effective gas exchange up to ∼288 mL/min/m(2) of oxygen and ∼685 mL/min/m(2) of carbon dioxide, approaching the gas exchange efficiency noted in the native lung. Testing several configurations of lung devices to explore various physical parameters of the device design, we concluded that thinner membranes and longer gas exchange distances result in improved hemoglobin saturation and increases in pO2. However, in the design space tested, these effects are relatively small compared to the improvement in overall oxygen and carbon dioxide transfer by increasing the blood flow rate. Finally, devices cultured with endothelial and parenchymal cells achieved similar gas exchange rates compared with acellular devices. Biomimetic blood oxygenator design opens the possibility of creating portable or implantable microfluidic devices that achieve efficient gas transfer while also maintaining physiologic conditions.

  14. Distinct Cellular Locations of Carbonic Anhydrases Mediate Carbon Dioxide Control of Stomatal Movements

    DOE PAGES

    Hu, Honghong; Rappel, Wouter-Jan; Occhipinti, Rossana; ...

    2015-09-28

    Elevated carbon dioxide (CO 2) in leaves closes stomatal apertures. Research has shown key functions of the β-carbonic anhydrases (βCA1 and βCA4) in rapid CO 2-induced stomatal movements by catalytic transmission of the CO 2 signal in guard cells. But, the underlying mechanisms remain unclear, because initial studies indicate that these Arabidopsis (Arabidopsis thaliana) βCAs are targeted to distinct intracellular compartments upon expression in tobacco (Nicotiana benthamiana) cells. Which cellular location of these enzymes plays a key role in native guard cells in CO 2-regulated stomatal movements remains unknown. We express fluorescently tagged CAs in guard cells of ca1ca4 double-mutantmore » plants and show that the specific locations of βCA4 at the plasma membrane and βCA1 in native guard cell chloroplasts each can mediate rapid CO 2 control of stomatal movements. Localization and complementation analyses using a mammalian αCAII-yellow fluorescent protein in guard cells further show that cytoplasmic localization is also sufficient to restore CO 2 regulation of stomatal conductance. Mathematical modeling of cellular CO 2 catalysis suggests that the dynamics of the intracellular HCO 3 - concentration change in guard cells can be driven by plasma membrane and cytoplasmic localizations of CAs but not as clearly by chloroplast targeting. Therefore, modeling supports the notion that the intracellular HCO 3 - concentration dynamics in guard cells are a key mechanism in mediating CO 2 -regulated stomatal movements but that an additional chloroplast role of CAs exists that has yet to be identified.« less

  15. Cellular thermotolerance is inheritable from Holstein cattle cloned with ooplasts of Taiwan native yellow cattle.

    PubMed

    Kesorn, Piyawit; Lee, Jai-Wei; Wu, Hung-Yi; Ju, Jyh-Cherng; Peng, Shao-Yu; Liu, Shyh-Shyan; Wu, Hsi-Hsun; Shen, Perng-Chih

    2017-01-15

    We have previously demonstrated that the somatic cells from cattle cloned with Holstein (H) donor cells and Taiwan native yellow cattle (Y) ooplasm (Yo-Hd) had better thermotolerance than those from cattle cloned with both Holstein donor cells and ooplasm (Ho-Hd). The present study aimed to investigate whether the cellular thermotolerance of these cloned cattle is transmissible to their offspring (Ho-Hd-F1 and Yo-Hd-F1). Thermotolerance of ear fibroblasts derived from these cloned cattle and their offspring were analyzed. Polymorphisms in mitochondrial DNA (mtDNA) D-loop of ear fibroblasts derived from Yo-Hd and Yo-Hd-F1 indicated that the cytoplasm is originated from Bos indicus (Y). After heat shock, the apoptotic rates, B-cell lymphoma 2-associated X protein/B-cell lymphoma 2 ratios, and relative expression levels of cysteine-aspartic proteases (caspases)-3, -8, and -9 of ear fibroblasts with Y-originated cytoplasm (including Y, Yo-Hd, and Yo-Hd-F1) were lower (P < 0.05) than those of ear fibroblasts with H-originated cytoplasm (including H, Ho-Hd, and Ho-Hd-F1). In contrast, the relative level of HSP-70 was higher (P < 0.05) in ear fibroblasts with Y-originated cytoplasm than that of with H-originated cytoplasm. Based on our results, thermotolerance of ear fibroblasts derived from Yo-Hd and Yo-Hd-F1 cattle is better and can be transmitted, at least at the cellular level, to their offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Axl as a mediator of cellular growth and survival.

    PubMed

    Axelrod, Haley; Pienta, Kenneth J

    2014-10-15

    The control of cellular growth and proliferation is key to the maintenance of homeostasis. Survival, proliferation, and arrest are regulated, in part, by Growth Arrest Specific 6 (Gas6) through binding to members of the TAM receptor tyrosine kinase family. Activation of the TAM receptors leads to downstream signaling through common kinases, but the exact mechanism within each cellular context varies and remains to be completely elucidated. Deregulation of the TAM family, due to its central role in mediating cellular proliferation, has been implicated in multiple diseases. Axl was cloned as the first TAM receptor in a search for genes involved in the progression of chronic to acute-phase leukemia, and has since been established as playing a critical role in the progression of cancer. The oncogenic nature of Axl is demonstrated through its activation of signaling pathways involved in proliferation, migration, inhibition of apoptosis, and therapeutic resistance. Despite its recent discovery, significant progress has been made in the development of effective clinical therapeutics targeting Axl. In order to accurately define the role of Axl in normal and diseased processes, it must be analyzed in a cell type-specific context.

  17. Context Specificity of Stress-activated Mitogen-activated Protein (MAP) Kinase Signaling: The Story as Told by Caenorhabditis elegans.

    PubMed

    Andrusiak, Matthew G; Jin, Yishi

    2016-04-08

    Stress-associated p38 and JNK mitogen-activated protein (MAP) kinase signaling cascades trigger specific cellular responses and are involved in multiple disease states. At the root of MAP kinase signaling complexity is the differential use of common components on a context-specific basis. The roundwormCaenorhabditis eleganswas developed as a system to study genes required for development and nervous system function. The powerful genetics ofC. elegansin combination with molecular and cellular dissections has led to a greater understanding of how p38 and JNK signaling affects many biological processes under normal and stress conditions. This review focuses on the studies revealing context specificity of different stress-activated MAPK components inC. elegans. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Cellular therapies supplement: strategies for improving transplant efficiency in the context of cellular therapeutics.

    PubMed

    Jimenez, Antonio; Fung, Henry C; Christopherson, Kent W

    2011-11-01

    The field of hematopoietic stem cell transplantation (HSCT) has overcome many obstacles that have led to our current clinical ability to utilize cells collected from marrow, mobilized peripheral blood, or umbilical cord blood for the treatment of malignant and nonmalignant hematologic diseases. It is in this context that it becomes evident that future progress will lie in our development of an understanding of the biology by which the process of HSCT is regulated. By understanding the cellular components and the mechanisms by which HSCT is either enhanced or suppressed it will then be possible to design therapeutic strategies to improve rates of engraftment that will have a positive impact on immune reconstitution post-HSCT. In this review we focus primarily on allogeneic hematopoietic stem cell transplantation (allo-HSCT), the current challenges associated with allo-HSCT, and some developing strategies to improve engraftment in this setting. © 2011 American Association of Blood Banks.

  19. Binding affinity of amyloid oligomers to cellular membranes is a generic indicator of cellular dysfunction in protein misfolding diseases

    PubMed Central

    Evangelisti, Elisa; Cascella, Roberta; Becatti, Matteo; Marrazza, Giovanna; Dobson, Christopher M.; Chiti, Fabrizio; Stefani, Massimo; Cecchi, Cristina

    2016-01-01

    The conversion of peptides or proteins from their soluble native states into intractable amyloid deposits is associated with a wide range of human disorders. Misfolded protein oligomers formed during the process of aggregation have been identified as the primary pathogenic agents in many such conditions. Here, we show the existence of a quantitative relationship between the degree of binding to neuronal cells of different types of oligomers formed from a model protein, HypF-N, and the GM1 content of the plasma membranes. In addition, remarkably similar behavior is observed for oligomers of the Aβ42 peptide associated with Alzheimer’s disease. Further analysis has revealed the existence of a linear correlation between the level of the influx of Ca2+ across neuronal membranes that triggers cellular damage, and the fraction of oligomeric species bound to the membrane. Our findings indicate that the susceptibility of neuronal cells to different types of misfolded oligomeric assemblies is directly related to the extent of binding of such oligomers to the cellular membrane. PMID:27619987

  20. SRD5A1 Genetic Variation and Prostate Cancer Epidemiology

    DTIC Science & Technology

    2005-05-01

    DATES COVERED (Leave blank) May 2005 Annual Summary (1 May 2004 - 30 Apr 2005) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS SRD5A1 Genetic Variation and...secondary structure of the luciferase+ SRD5A1 3’-UTR mRNA was so different from the native SRD5Al message, that the 3’-UTR variants should be tested...in the context of a native mRNA. A eukaryotic expression vector containing 850bp of the human SRD5A1 promoter was seamlessly cloned onto the 5’ end of

  1. Salmon cycles: Influences of a science field study immersion experience with Native American young women

    NASA Astrophysics Data System (ADS)

    Ault, Phyllis Campbell

    Native Americans, and particularly Native women, are not proportionally represented in higher education, or in science, mathematics, technology, and engineering fields. This study examined an out-of-school science education program which combined traditional Native American cultural and ecological knowledge with Western science in conducting authentic field studies. A qualitative, embedded case study approach was used to explore how young Native American women were influenced by an out-of-school program integrating a culturally responsive approach and experiential research projects. Within this context of combined cultures, three significant domains emerged: field study in science, sense of place, and networks of supportive relationships. These domains interacted with the aspirations of the eight Native women in the study. Using interview transcripts, reflective writings, and participant data, the study explored the blending of Indigenous and Western science in "communities of practice" (e.g., fisheries biology, restoration ecology, and forestry). The eight Native women in this study participated as young adolescents and later returned as counselors. Interviews focused on their postsecondary aspirations and choices. Findings validated previous research on the value of infusing Traditional Ecological Knowledge and Western science for Native students. The study found the combination of culturally responsive pedagogy and authentic experiences in "communities-of-practice" held a beneficial influence on postsecondary pathways. The importance of respect and friendships fostered through the program was associated with resilience and perseverance in educational aspirations. Immersion in field study with Native peers as well as Native and non-Native researchers was a catalyst for all the women, in a number of different ways, such as: deeper involvement with the Native community, strengthening cultural and academic identity, inspiration to learn more about their cultural heritage, and interest in pursuing science or science-related careers. Commitments to "giving back" to the community, stewardship, and activism emerged as significant outcomes. The experience created a safe, empowering place to be Native, "crazy, a scientist, and a fish geek"---all at once.

  2. The Effects of L2 Experience and Vowel Context on the Perceptual Assimilation of English Fricatives by L2 Thai Learners

    ERIC Educational Resources Information Center

    Kitikanan, Patchanok

    2017-01-01

    The aim of this study is to investigate the effect of vowel context and language experience in the perceived similarity between L2 English fricatives and Thai sounds. The target English sounds being investigated were the sounds /v, f, w, ?, t?, s, ð, d, z, ?, t??/. These sounds were elicited from four native English speakers in words in onset…

  3. Comparative analysis of the immune responses induced by native versus recombinant versions of the ASP-based vaccine against the bovine intestinal parasite Cooperia oncophora.

    PubMed

    González-Hernández, Ana; Borloo, Jimmy; Peelaers, Iris; Casaert, Stijn; Leclercq, Georges; Claerebout, Edwin; Geldhof, Peter

    2018-01-01

    The protective capacities of a native double-domain activation-associated secreted protein (ndd-ASP)-based vaccine against the cattle intestinal nematode Cooperia oncophora has previously been demonstrated. However, protection analysis upon vaccination with a recombinantly produced antigen has never been performed. Therefore, the aim of the current study was to test the protective potential of a Pichia-produced double-domain ASP (pdd-ASP)-based vaccine against C. oncophora. Additionally, we aimed to compare the cellular and humoral mechanisms underlying the vaccine-induced responses by the native (ndd-ASP) and recombinant vaccines. Immunisation of cattle with the native C. oncophora vaccine conferred significant levels of protection after an experimental challenge infection, whereas the recombinant vaccine did not. Moreover, vaccination with ndd-ASP resulted in a higher proliferation of CD4-T cells both systemically and in the small intestinal mucosa when compared with animals vaccinated with the recombinant antigen. In terms of humoral response, although both native and recombinant vaccines induced similar levels of antibodies, animals vaccinated with the native vaccine were able to raise antibodies with greater specificity towards ndd-ASP in comparison with antibodies raised by vaccination with the recombinant vaccine, suggesting a differential immune recognition towards the ndd-ASP and pdd-ASP. Finally, the observation that animals displaying antibodies with higher percentages of recognition towards ndd-ASP also exhibited the lowest egg counts suggests a potential relationship between antibody specificity and protection. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  4. Analysis of Protein Interactions at Native Chloroplast Membranes by Ellipsometry

    PubMed Central

    Kriechbaumer, Verena; Nabok, Alexei; Mustafa, Mohd K.; Al-Ammar, Rukaiah; Tsargorodskaya, Anna; Smith, David P.; Abell, Ben M.

    2012-01-01

    Membrane bound receptors play vital roles in cell signaling, and are the target for many drugs, yet their interactions with ligands are difficult to study by conventional techniques due to the technical difficulty of monitoring these interactions in lipid environments. In particular, the ability to analyse the behaviour of membrane proteins in their native membrane environment is limited. Here, we have developed a quantitative approach to detect specific interactions between low-abundance chaperone receptors within native chloroplast membranes and their soluble chaperone partners. Langmuir-Schaefer film deposition was used to deposit native chloroplasts onto gold-coated glass slides, and interactions between the molecular chaperones Hsp70 and Hsp90 and their receptors in the chloroplast membranes were detected and quantified by total internal reflection ellipsometry (TIRE). We show that native chloroplast membranes deposited on gold-coated glass slides using Langmuir-Schaefer films retain functional receptors capable of binding chaperones with high specificity and affinity. Taking into account the low chaperone receptor abundance in native membranes, these binding properties are consistent with data generated using soluble forms of the chloroplast chaperone receptors, OEP61 and Toc64. Therefore, we conclude that chloroplasts have the capacity to selectively bind chaperones, consistent with the notion that chaperones play an important role in protein targeting to chloroplasts. Importantly, this method of monitoring by TIRE does not require any protein labelling. This novel combination of techniques should be applicable to a wide variety of membranes and membrane protein receptors, thus presenting the opportunity to quantify protein interactions involved in fundamental cellular processes, and to screen for drugs that target membrane proteins. PMID:22479632

  5. Correlative 3D superresolution fluorescence and electron microscopy reveal the relationship of mitochondrial nucleoids to membranes

    PubMed Central

    Kopek, Benjamin G.; Shtengel, Gleb; Xu, C. Shan; Clayton, David A.; Hess, Harald F.

    2012-01-01

    Microscopic images of specific proteins in their cellular context yield important insights into biological processes and cellular architecture. The advent of superresolution optical microscopy techniques provides the possibility to augment EM with nanometer-resolution fluorescence microscopy to access the precise location of proteins in the context of cellular ultrastructure. Unfortunately, efforts to combine superresolution fluorescence and EM have been stymied by the divergent and incompatible sample preparation protocols of the two methods. Here, we describe a protocol that preserves both the delicate photoactivatable fluorescent protein labels essential for superresolution microscopy and the fine ultrastructural context of EM. This preparation enables direct 3D imaging in 500- to 750-nm sections with interferometric photoactivatable localization microscopy followed by scanning EM images generated by focused ion beam ablation. We use this process to “colorize” detailed EM images of the mitochondrion with the position of labeled proteins. The approach presented here has provided a new level of definition of the in vivo nature of organization of mitochondrial nucleoids, and we expect this straightforward method to be applicable to many other biological questions that can be answered by direct imaging. PMID:22474357

  6. Native root-associated bacteria rescue a plant from a sudden-wilt disease that emerged during continuous cropping

    PubMed Central

    Santhanam, Rakesh; Luu, Van Thi; Weinhold, Arne; Goldberg, Jay; Oh, Youngjoo; Baldwin, Ian T.

    2015-01-01

    Plants maintain microbial associations whose functions remain largely unknown. For the past 15 y, we have planted the annual postfire tobacco Nicotiana attenuata into an experimental field plot in the plant’s native habitat, and for the last 8 y the number of plants dying from a sudden wilt disease has increased, leading to crop failure. Inadvertently we had recapitulated the common agricultural dilemma of pathogen buildup associated with continuous cropping for this native plant. Plants suffered sudden tissue collapse and black roots, symptoms similar to a Fusarium–Alternaria disease complex, recently characterized in a nearby native population and developed into an in vitro pathosystem for N. attenuata. With this in vitro disease system, different protection strategies (fungicide and inoculations with native root-associated bacterial and fungal isolates), together with a biochar soil amendment, were tested further in the field. A field trial with more than 900 plants in two field plots revealed that inoculation with a mixture of native bacterial isolates significantly reduced disease incidence and mortality in the infected field plot without influencing growth, herbivore resistance, or 32 defense and signaling metabolites known to mediate resistance against native herbivores. Tests in a subsequent year revealed that a core consortium of five bacteria was essential for disease reduction. This consortium, but not individual members of the root-associated bacteria community which this plant normally recruits during germination from native seed banks, provides enduring resistance against fungal diseases, demonstrating that native plants develop opportunistic mutualisms with prokaryotes that solve context-dependent ecological problems. PMID:26305938

  7. Creating Context for the Use of DNA Adduct Data in Risk Assessment

    EPA Science Inventory

    Assessments of human cancer risk require the integration of diverse types of data. Advancing technologies for quantitative measurements at the sub-cellular domain raise the critical issue of interpretation and use of DNA adduct data in context with current understanding of cancer...

  8. Word recognition and phonetic structure acquisition: Possible relations

    NASA Astrophysics Data System (ADS)

    Morgan, James

    2002-05-01

    Several accounts of possible relations between the emergence of the mental lexicon and acquisition of native language phonological structure have been propounded. In one view, acquisition of word meanings guides infants' attention toward those contrasts that are linguistically significant in their language. In the opposing view, native language phonological categories may be acquired from statistical patterns of input speech, prior to and independent of learning at the lexical level. Here, a more interactive account will be presented, in which phonological structure is modeled as emerging consequentially from the self-organization of perceptual space underlying word recognition. A key prediction of this model is that early native language phonological categories will be highly context specific. Data bearing on this prediction will be presented which provide clues to the nature of infants' statistical analysis of input.

  9. A Novel Method for Sampling Alpha-Helical Protein Backbones

    DOE R&D Accomplishments Database

    Fain, Boris; Levitt, Michael

    2001-01-01

    We present a novel technique of sampling the configurations of helical proteins. Assuming knowledge of native secondary structure, we employ assembly rules gathered from a database of existing structures to enumerate the geometrically possible 3-D arrangements of the constituent helices. We produce a library of possible folds for 25 helical protein cores. In each case the method finds significant numbers of conformations close to the native structure. In addition we assign coordinates to all atoms for 4 of the 25 proteins. In the context of database driven exhaustive enumeration our method performs extremely well, yielding significant percentages of structures (0.02%--82%) within 6A of the native structure. The method's speed and efficiency make it a valuable contribution towards the goal of predicting protein structure.

  10. Hodgkin lymphoma incidence in California Hispanics: Influence of nativity and tumor Epstein–Barr virus

    PubMed Central

    Clarke, C. A.; Chang, E. T.; Yang, J.; Gomez, S. L.; Keegan, T. H.

    2017-01-01

    Purpose For classical Hodgkin lymphoma (HL), migrant studies could elucidate contributions of environmental factors (including Epstein–Barr virus (EBV)) to the lower rates in non-whites. Given the well-described etiologic complexity of HL, this research requires a large, immigrant population, such as California Hispanics. Methods With 1988–2004 California Cancer Registry data (2,595 Hispanic, 8,637 white HL cases) and tumor cell EBV status on a subset (218 Hispanics, 656 whites), we calculated ethnicity- and nativity-specific HL incidence rates simultaneously by age, sex, and histologic subtype, and tumor cell EBV prevalence. Results Compared with white rates, Hispanic HL rates were lower overall (70 %) and for nodular sclerosis HL, particularly among young adults (60–65 % for females). However, they were higher among children (200 %) and older adults, and for mixed cellularity HL. Compared with rates in foreign-born Hispanics, rates in US-born Hispanics were higher among young adults (>threefold in females), lower for children and adults over age 70, and consistently intermediate compared with rates in whites. EBV tumor prevalence was 67, 32, and 23 % among foreign-born Hispanics, US-born Hispanics, and whites, respectively, although with variation by age, sex, and histology. Conclusions Findings strongly implicate environmental influences, such as nativity-related sociodemographic differences, on HL occurrence. In addition, lower young adult rates and higher EBV prevalence in US-born Hispanics than in whites raise questions about the duration/extent of environmental change for affecting HL rates and also point to ethnic differences in genetic susceptibility. Lesser variation in mixed cellularity HL rates and greater variation in rates for females across groups suggest less modifiable factors interacting with environmental influences. PMID:24722952

  11. Comparison of alpha 1A- and alpha 1B-adrenoceptor coupling to inositol phosphate formation in rat kidney.

    PubMed

    Büscher, R; Erdbrügger, W; Philipp, T; Brodde, O E; Michel, M C

    1994-12-01

    We have compared the coupling mechanisms of rat renal alpha 1A- and alpha 1B-like adrenoceptors to inositol phosphate formation. The experiments were performed in parallel in native renal tissue preparations and in those where alpha 1B-adrenoceptors had been inactivated by treatment with 10 mumol/l chloroethylclonidine for 30 min at 37 degrees C; renal slices were used in most experiments but isolated renal cells were also used in some cases. The Ca2+ chelating agent, EGTA (5 mmol/l), reduced noradrenaline-stimulated inositol phosphate formation in native but enhanced it in chloroethylclonidine-treated renal slices. The inhibitory effect of EGTA was not mimicked by 100 nmol/l nifedipine. Inactivation of 87% of cellular Gi by 16-20 h treatment with 500 ng/ml pertussis toxin did not significantly affect noradrenaline-stimulated inositol phosphate formation in isolated renal cells but abolished the inhibitory effect of chloroethylclonidine. The adenylate cyclase activator, forskolin (20 mumol/l), inhibited noradrenaline-stimulated inositol phosphate formation in native and chloroethylclonidine-treated slices, and the inhibitory effects of chloroethylclonidine treatment and forskolin were additive. We conclude that in rat kidney inositol phosphate formation via alpha 1B-like adrenoceptors may involve the influx of extracellular Ca2+ and a pertussis toxin-sensitive G-protein but is insensitive to inhibition by forskolin. In contrast alpha 1A-like adrenoceptor-mediated inositol phosphate formation does not require the presence of extracellular Ca2+ or of Gi and is sensitive to inhibition by forskolin. In comparison to published data from other model systems we further conclude that the signaling mechanisms of alpha 1-adrenoceptor subtypes may depend on their cellular environment.

  12. Asynchronous adaptive time step in quantitative cellular automata modeling

    PubMed Central

    Zhu, Hao; Pang, Peter YH; Sun, Yan; Dhar, Pawan

    2004-01-01

    Background The behaviors of cells in metazoans are context dependent, thus large-scale multi-cellular modeling is often necessary, for which cellular automata are natural candidates. Two related issues are involved in cellular automata based multi-cellular modeling: how to introduce differential equation based quantitative computing to precisely describe cellular activity, and upon it, how to solve the heavy time consumption issue in simulation. Results Based on a modified, language based cellular automata system we extended that allows ordinary differential equations in models, we introduce a method implementing asynchronous adaptive time step in simulation that can considerably improve efficiency yet without a significant sacrifice of accuracy. An average speedup rate of 4–5 is achieved in the given example. Conclusions Strategies for reducing time consumption in simulation are indispensable for large-scale, quantitative multi-cellular models, because even a small 100 × 100 × 100 tissue slab contains one million cells. Distributed and adaptive time step is a practical solution in cellular automata environment. PMID:15222901

  13. The constant threat from a non-native predator increases tail muscle and fast-start swimming performance in Xenopus tadpoles.

    PubMed

    Mori, Tsukasa; Yanagisawa, Yukio; Kitani, Yoichiro; Yamamoto, Goshi; Goto-Inoue, Naoko; Kimura, Tadashi; Kashiwagi, Keiko; Kashiwagi, Akihiko

    2017-11-15

    Predator-induced phenotypic plasticity is the ability of prey to adapt to their native predator. However, owing to environmental changes, encounters with unknown predators are inevitable. Therefore, study of prey and non-native predator interaction will reveal the primary stages of adaptive strategies in prey-predator interactions in the context of evolutionary processes. Here, Xenopus tadpoles exposed to a non-native predator, a larval salamander, showed a significant increase in body weight and tail length to body length ratio. The T max 2 test indicated a significant enhancement of the tail muscle and decrease in the relative ventral fin height in tadpoles exposed to predation risk, leading to significantly higher average swimming speeds. The analysis of muscle-related metabolites revealed that sarcosine increased significantly in tadpoles exposed to non-native predators. Multiple linear regression analysis of the fast-start swimming pattern showed that the fast-start swimming speed was determined by the time required for a tadpole to bend its body away from the threat (C-start) and the angle at which it was bent. In conclusion, morphological changes in tadpoles were functionally adaptive and induced by survival behaviors of Xenopus tadpoles against non-native predators. © 2017. Published by The Company of Biologists Ltd.

  14. [Neurotransmitter mechanisms of context-dependent behavior].

    PubMed

    D'iakonova, V E

    2012-01-01

    The influence of context on behavioral choice is well known. Context can refer to behavioral state of an animal and to external factors such as season, presence of other individuals or food availability. How external and internal factors influencing decision-making are translated at the cellular level? I review the recent neuroethological data that strongly suggest that context reflects in content of neuroactive substances (neurotransmitters, modulators, hormones) that present in the extraneuronal milieu, while heterochemical neuronal microenvironment in its turn impacts motor program selection.

  15. A Perceptual Phonetic Similarity Space for Languages: Evidence from Five Native Language Listener Groups1

    PubMed Central

    Bradlow, Ann; Clopper, Cynthia; Smiljanic, Rajka; Walter, Mary Ann

    2010-01-01

    The goal of the present study was to devise a means of representing languages in a perceptual similarity space based on their overall phonetic similarity. In Experiment 1, native English listeners performed a free classification task in which they grouped 17 diverse languages based on their perceived phonetic similarity. A similarity matrix of the grouping patterns was then submitted to clustering and multidimensional scaling analyses. In Experiment 2, an independent group of native English listeners sorted the group of 17 languages in terms of their distance from English. Experiment 3 repeated Experiment 2 with four groups of non-native English listeners: Dutch, Mandarin, Turkish and Korean listeners. Taken together, the results of these three experiments represent a step towards establishing an approach to assessing the overall phonetic similarity of languages. This approach could potentially provide the basis for developing predictions regarding foreign-accented speech intelligibility for various listener groups, and regarding speech perception accuracy in the context of background noise in various languages. PMID:21179563

  16. Comparative water use of native and invasive plants at multiple scales: a global meta-analysis.

    PubMed

    Cavaleri, Molly A; Sack, Lawren

    2010-09-01

    Ecohydrology and invasive ecology have become increasingly important in the context of global climate change. This study presents the first in-depth analysis of the water use of invasive and native plants of the same growth form at multiple scales: leaf, plant, and ecosystem. We reanalyzed data for several hundred native and invasive species from over 40 published studies worldwide to glean global trends and to highlight how patterns vary depending on both scale and climate. We analyzed all pairwise combinations of co-occurring native and invasive species for higher comparative resolution of the likelihood of an invasive species using more water than a native species and tested for significance using bootstrap methods. At each scale, we found several-fold differences in water use between specific paired invasive and native species. At the leaf scale, we found a strong tendency for invasive species to have greater stomatal conductance than native species. At the plant scale, however, natives and invasives were equally likely to have the higher sap flow rates. Available data were much fewer for the ecosystem scale; nevertheless, we found that invasive-dominated ecosystems were more likely to have higher sap flow rates per unit ground area than native-dominated ecosystems. Ecosystem-scale evapotranspiration, on the other hand, was equally likely to be greater for systems dominated by invasive and native species of the same growth form. The inherent disconnects in the determination of water use when changing scales from leaf to plant to ecosystem reveal hypotheses for future studies and a critical need for more ecosystem-scale water use measurements in invasive- vs. native-dominated systems. The differences in water use of native and invasive species also depended strongly on climate, with the greater water use of invasives enhanced in hotter, wetter climates at the coarser scales.

  17. Biotechnologies as a Context for Enhancing Junior High-School Students' Ability to Ask Meaningful Questions about Abstract Biological Processes.

    ERIC Educational Resources Information Center

    Olsher, G.; Dreyfus, A.

    1999-01-01

    Suggests a new approach to teaching about biochemical cellular processes by stimulating student interest in those biochemical processes that allowed for the outcomes of modern biotechnologies. Discusses the development of students' ability to ask meaningful questions about intra-cellular processes, and the resulting meaningful learning of relevant…

  18. DIMENSION-BASED STATISTICAL LEARNING OF VOWELS

    PubMed Central

    Liu, Ran; Holt, Lori L.

    2015-01-01

    Speech perception depends on long-term representations that reflect regularities of the native language. However, listeners rapidly adapt when speech acoustics deviate from these regularities due to talker idiosyncrasies such as foreign accents and dialects. To better understand these dual aspects of speech perception, we probe native English listeners’ baseline perceptual weighting of two acoustic dimensions (spectral quality and vowel duration) towards vowel categorization and examine how they subsequently adapt to an “artificial accent” that deviates from English norms in the correlation between the two dimensions. At baseline, listeners rely relatively more on spectral quality than vowel duration to signal vowel category, but duration nonetheless contributes. Upon encountering an “artificial accent” in which the spectral-duration correlation is perturbed relative to English language norms, listeners rapidly down-weight reliance on duration. Listeners exhibit this type of short-term statistical learning even in the context of nonwords, confirming that lexical information is not necessary to this form of adaptive plasticity in speech perception. Moreover, learning generalizes to both novel lexical contexts and acoustically-distinct altered voices. These findings are discussed in the context of a mechanistic proposal for how supervised learning may contribute to this type of adaptive plasticity in speech perception. PMID:26280268

  19. Sign Lowering and Phonetic Reduction in American Sign Language.

    PubMed

    Tyrone, Martha E; Mauk, Claude E

    2010-04-01

    This study examines sign lowering as a form of phonetic reduction in American Sign Language. Phonetic reduction occurs in the course of normal language production, when instead of producing a carefully articulated form of a word, the language user produces a less clearly articulated form. When signs are produced in context by native signers, they often differ from the citation forms of signs. In some cases, phonetic reduction is manifested as a sign being produced at a lower location than in the citation form. Sign lowering has been documented previously, but this is the first study to examine it in phonetic detail. The data presented here are tokens of the sign WONDER, as produced by six native signers, in two phonetic contexts and at three signing rates, which were captured by optoelectronic motion capture. The results indicate that sign lowering occurred for all signers, according to the factors we manipulated. Sign production was affected by several phonetic factors that also influence speech production, namely, production rate, phonetic context, and position within an utterance. In addition, we have discovered interesting variations in sign production, which could underlie distinctions in signing style, analogous to accent or voice quality in speech.

  20. Culture, demographics, and critical care issues: an overview.

    PubMed

    Núñez, Germán R

    2003-10-01

    The population dynamic and the immigration trends in the United States continue to challenge health care professionals who each day must serve an increasingly diverse population. Today's physicians must not only have a solid background in medical sciences but they must also have knowledge of how culture, race, and ethnicity impact how patients view and accept traditional Western practices. Whether doctors and patients are close in the "context spectrum" will often determine their ability to communicate beyond the spoken language. According to a report of the American Medical Association, by the year 2000, out of a total 812,770 physicians, only 2.5% were Black, 3.5% Hispanic, and 8.9% Asian. Only a fraction of a percent was American Native/Alaskan Native. Therefore, the majority of the physicians are Caucasian, and it could be assumed that they would likely be accustomed to high-context communication styles. The gross of the demographic changes and population increases in the United States during the past 10 years can be attributed to immigration from regions of the world where low-context communication styles are prevalent. Such differences between physicians and patients can create difficult, tense situations in an already charged atmosphere as can be that of a critical care unit.

  1. Bioengineering pediatric scaffold-free auricular cartilaginous constructs.

    PubMed

    Akbari, Pedram; Waldman, Stephen D; Cushing, Sharon L; Papsin, Blake C; Propst, Evan J; Weber, Joanna F; Yeger, Herman; Farhat, Walid A

    2017-05-01

    The use of exogenous materials as scaffolds in cartilage tissue engineering has limited the clinical application of resultant constructs due to the risk of postoperative complications. In an effort to minimize such complications, we aim to generate human, scaffold-free auricular cartilaginous constructs. Laboratory study using pediatric auricular cartilage. Remnant, normal pediatric auricular cartilage samples that would have otherwise been discarded were collected and digested to free cells. Harvested cells were cultured and expanded in vitro for two passages and plated as micromass cultures. The culture medium was replaced with a chemically defined chondrogenic medium, and cellular monolayers surrounding micromass cultures were continuously scraped off. Constructs were allowed to mature for a period of 8 weeks. Micromass constructs showed mechanical stability and structurally resembled native auricular tissue, with a perichondrium-like layer of cells surrounding the inner cartilaginous zone. Constructs accumulated equivalent sulphated glycosaminoglycan and 50% of collagen content compared to native auricular cartilage by mass, while displaying 156% more cellularity. High-density micromass cultures of pediatric auricular chondrocytes can generate stable cartilaginous constructs following prolonged chondrogenic inductions in vitro. This technique is an essential step toward the development of three-dimensional constructs to recreate clinically applicable auricular cartilaginous constructs. NA. Laryngoscope, 127:E153-E158, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  2. In vitro reconstruction of hybrid vascular tissue. Hierarchic and oriented cell layers.

    PubMed

    Kanda, K; Matsuda, T; Oka, T

    1993-01-01

    Hybrid vascular tissue was hierarchically reconstructed in vitro. A hybrid medial layer composed of type I collagen gel, in which SMCs derived from a mongrel dog were embedded, was formed on the inner surface of a compliant porous polyurethane graft (internal diameter = 3 mm). Endothelial cells (ECs) from the same animal were seeded and cultured on the hybrid media to build an intimal layer. Subsequently, hierarchically structured grafts constructed in this manner were subjected to pulsatile flow (flow rate: 8.5 ml/min; frequency: 60 rpm; amplitude: 5% of graft outer diameter) of culture medium (Medium 199 supplemented with 20% fetal calf serum). After stress loading for as long as 10 days, tissues were morphologically investigated with a light microscope and a scanning electron microscope. Inner surfaces of the hybrid tissues were covered with EC monolayers that aligned along the direction of the flow (i.e., longitudinally). However, SMCs beneath the intima aligned in the circumferential direction. These cellular orientations resembled those in native muscular arteries. The pulsatile stress loaded hybrid tissue mimicked native muscular arteries with respect to hierarchic structure and cellular orientation. In vitro mechanical stress loading on a hybrid graft might provide a high degree of integrity in terms of tissue structure that promises high tolerance toward hydrodynamic stress and regulation of vasomotor tone upon implantation.

  3. The Road to Shadowland

    ERIC Educational Resources Information Center

    Divakaruni, Chitra Banerjee

    2010-01-01

    Divakaruni reflects on her path to becoming an author for children, including her formative encounters with stories told by her grandfather in her native India, and experiences as a mother and as an Indian woman in the post-9/11 context of the United States.

  4. Considering the Lives of Microbes in Microbial Communities.

    PubMed

    Shank, Elizabeth A

    2018-01-01

    Over the last decades, sequencing technologies have transformed our ability to investigate the composition and functional capacity of microbial communities. Even so, critical questions remain about these complex systems that cannot be addressed by the bulk, community-averaged data typically provided by sequencing methods. In this Perspective, I propose that future advances in microbiome research will emerge from considering "the lives of microbes": we need to create methods to explicitly interrogate how microbes exist and interact in native-setting-like microenvironments. This approach includes developing approaches that expose the phenotypic heterogeneity of microbes; exploring the effects of coculture cues on cellular differentiation and metabolite production; and designing visualization systems that capture features of native microbial environments while permitting the nondestructive observation of microbial interactions over space and time with single-cell resolution.

  5. A generic screening platform for inhibitors of virus induced cell fusion using cellular electrical impedance

    PubMed Central

    Watterson, Daniel; Robinson, Jodie; Chappell, Keith J.; Butler, Mark S.; Edwards, David J.; Fry, Scott R.; Bermingham, Imogen M.; Cooper, Matthew A.; Young, Paul R.

    2016-01-01

    Fusion of the viral envelope with host cell membranes is an essential step in the life cycle of all enveloped viruses. Despite such a clear target for antiviral drug development, few anti-fusion drugs have progressed to market. One significant hurdle is the absence of a generic, high-throughput, reproducible fusion assay. Here we report that real time, label-free measurement of cellular electrical impedance can quantify cell-cell fusion mediated by either individually expressed recombinant viral fusion proteins, or native virus infection. We validated this approach for all three classes of viral fusion and demonstrated utility in quantifying fusion inhibition using antibodies and small molecule inhibitors specific for dengue virus and respiratory syncytial virus. PMID:26976324

  6. Inhibiting host-pathogen interactions using membrane-based nanostructures.

    PubMed

    Bricarello, Daniel A; Patel, Mira A; Parikh, Atul N

    2012-06-01

    Virulent strains of bacteria and viruses recognize host cells by their plasma membrane receptors and often exploit the native translocation machinery to invade the cell. A promising therapeutic concept for early interruption of pathogen infection is to subvert this pathogenic trickery using exogenously introduced decoys that present high-affinity mimics of cellular receptors. This review highlights emerging applications of molecularly engineered lipid-bilayer-based nanostructures, namely (i) functionalized liposomes, (ii) supported colloidal bilayers or protocells and (iii) reconstituted lipoproteins, which display functional cellular receptors in optimized conformational and aggregative states. These decoys outcompete host cell receptors by preferentially binding to and neutralizing virulence factors of both bacteria and viruses, thereby promising a new approach to antipathogenic therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Measurement uncertainty evaluation of cellular spheroids surface tension in compressing tests using Young-Laplace equation

    NASA Astrophysics Data System (ADS)

    Beatrici, Anderson; Santos Baptista, Leandra; Mauro Granjeiro, José

    2018-03-01

    Regenerative Medicine comprises the Biotechnology, Tissue Engineering and Biometrology for stem cell therapy. Starting from stem cells extracted from the patient, autologous implant, these cells are cultured and differentiated into other tissues, for example, articular cartilage. These cells are reorganized into microspheres (cell spheroids). Such tissue units are recombined into functional tissues constructs that can be implanted in the injured region for regeneration. It is necessary the biomechanical characterization of these constructed to determine if their properties are similar to native tissue. In this study was carried out the modeling of the calculation of uncertainty of the surface tension of cellular spheroids with the use of the Young-Laplace equation. We obtained relative uncertainties about 10%.

  8. Fluorescent Reporters and Biosensors for Probing the Dynamic Behavior of Protein Kinases

    PubMed Central

    González-Vera, Juan A.; Morris, May C.

    2015-01-01

    Probing the dynamic activities of protein kinases in real-time in living cells constitutes a major challenge that requires specific and sensitive tools tailored to meet the particular demands associated with cellular imaging. The development of genetically-encoded and synthetic fluorescent biosensors has provided means of monitoring protein kinase activities in a non-invasive fashion in their native cellular environment with high spatial and temporal resolution. Here, we review existing technologies to probe different dynamic features of protein kinases and discuss limitations where new developments are required to implement more performant tools, in particular with respect to infrared and near-infrared fluorescent probes and strategies which enable improved signal-to-noise ratio and controlled activation of probes. PMID:28248276

  9. Amyloid Oligomers and Protofibrils, but Not Filaments, Self-Replicate from Native Lysozyme

    PubMed Central

    2015-01-01

    Self-assembly of amyloid fibrils is the molecular mechanism best known for its connection with debilitating human disorders such as Alzheimer’s disease but is also associated with various functional cellular responses. There is increasing evidence that amyloid formation proceeds along two distinct assembly pathways involving either globular oligomers and protofibrils or rigid monomeric filaments. Oligomers, in particular, have been implicated as the dominant molecular species responsible for pathogenesis. Yet the molecular mechanisms regulating their self-assembly have remained elusive. Here we show that oligomers/protofibrils and monomeric filaments, formed along distinct assembly pathways, display critical differences in their ability to template amyloid growth at physiological vs denaturing temperatures. At physiological temperatures, amyloid filaments remained stable but could not seed growth of native monomers. In contrast, oligomers and protofibrils not only remained intact but were capable of self-replication using native monomers as the substrate. Kinetic data further suggested that this prion-like growth mode of oligomers/protofibrils involved two distinct activities operating orthogonal from each other: autocatalytic self-replication of oligomers from native monomers and nucleated polymerization of oligomers into protofibrils. The environmental changes to stability and templating competence of these different amyloid species in different environments are likely to be important for understanding the molecular mechanisms underlying both pathogenic and functional amyloid self-assembly. PMID:24884889

  10. Amyloid oligomers and protofibrils, but not filaments, self-replicate from native lysozyme.

    PubMed

    Mulaj, Mentor; Foley, Joseph; Muschol, Martin

    2014-06-25

    Self-assembly of amyloid fibrils is the molecular mechanism best known for its connection with debilitating human disorders such as Alzheimer's disease but is also associated with various functional cellular responses. There is increasing evidence that amyloid formation proceeds along two distinct assembly pathways involving either globular oligomers and protofibrils or rigid monomeric filaments. Oligomers, in particular, have been implicated as the dominant molecular species responsible for pathogenesis. Yet the molecular mechanisms regulating their self-assembly have remained elusive. Here we show that oligomers/protofibrils and monomeric filaments, formed along distinct assembly pathways, display critical differences in their ability to template amyloid growth at physiological vs denaturing temperatures. At physiological temperatures, amyloid filaments remained stable but could not seed growth of native monomers. In contrast, oligomers and protofibrils not only remained intact but were capable of self-replication using native monomers as the substrate. Kinetic data further suggested that this prion-like growth mode of oligomers/protofibrils involved two distinct activities operating orthogonal from each other: autocatalytic self-replication of oligomers from native monomers and nucleated polymerization of oligomers into protofibrils. The environmental changes to stability and templating competence of these different amyloid species in different environments are likely to be important for understanding the molecular mechanisms underlying both pathogenic and functional amyloid self-assembly.

  11. Drug Offers as a Context for Violence Perpetration and Victimization

    PubMed Central

    Helm, Susana; Okamoto, Scott; Kaliades, Alexis; Giroux, Danielle

    2014-01-01

    Objective Drug use has been linked empirically with aggression and violence among youth in national and State of Hawai`i samples. However, the nature of this link and its implications for prevention are unclear. Therefore, this paper explores the intersection of drugs with aggression and violence by using the drug offer context as the unit of analysis. Method Native Hawaiian youth are sampled because substance use rates tend to be higher and onset tends to be earlier than their non-Hawaiian peers. Fourteen sex-specific focus group discussions were held with rural Native Hawaiian middle school students (N=64). Students discussed what they thought they would do in terms of drug refusal strategies in a variety of drug offer contexts. Results While aggression and violence were perceived to be socially inappropriate, students nonetheless felt drug use would be less socially competent. Narrative analyses indicated aggression and violence were perceived to function as potential drug refusal strategies. As proximal drug resistance, aggression and violence perpetration served as an immediate deterrent to the drug offerer, and thus drug use. As distal drug resistance, victimization served as a rationale for avoiding drug using contexts. Conclusions Implications are discussed in terms of prevention policy and practice, specifically in terms of a school-based prevention curriculum. Future research in Hawaiian epistemology and gendered approaches are warranted. PMID:24564559

  12. Urbanized landscapes favored by fig-eating birds increase invasive but not native juvenile strangler fig abundance.

    PubMed

    Caughlin, Trevor; Wheeler, Jessica H; Jankowski, Jill; Lichstein, Jeremy W

    2012-07-01

    Propagule pressure can determine the success or failure of invasive plant range expansion. Range expansion takes place at large spatial scales, often encompassing many types of land cover, yet the effect of landscape context on propagule pressure remains largely unknown. Many studies have reported a positive correlation between invasive plant abundance and human land use; increased propagule pressure in these landscapes may be responsible for this correlation. We tested the hypothesis that increased rates of seed dispersal by fig-eating birds, which are more common in urban habitats, result in an increase in invasive strangler fig abundance in landscapes dominated by human land use. We quantified abundance of an invasive species (Ficus microcarpa) and a native species (F. aurea) of strangler fig in plots spanning the entire range of human land use in South Florida, USA, from urban parking lots to native forest. We then compared models that predicted juvenile fig abundance based on distance to adult fig seed sources and fig-eating bird habitat quality with models that lacked one or both of these terms. The best model for juvenile invasive fig abundance included both distance to adult and fig-eating bird habitat terms, suggesting that landscape effects on invasive fig abundance are mediated by seed-dispersing birds. In contrast, the best model for juvenile native fig abundance included only presence/absence of adults, suggesting that distance from individual adult trees may have less effect on seed limitation for a native species compared to an invasive species undergoing range expansion. However, models for both species included significant effects of adult seed sources, implying that juvenile abundance is limited by seed arrival. This result was corroborated by a seed addition experiment that indicated that both native and invasive strangler figs were strongly seed limited. Understanding how landscape context affects the mechanisms of plant invasion may lead to better management techniques. Our results suggest that prioritizing removal of adult trees in sites with high fig-eating bird habitat may be the most effective method to control F. microcarpa abundance.

  13. Profound re-organization of cell surface proteome in equine retinal pigment epithelial cells in response to in vitro culturing.

    PubMed

    Szober, Christoph M; Hauck, Stefanie M; Euler, Kerstin N; Fröhlich, Kristina J H; Alge-Priglinger, Claudia; Ueffing, Marius; Deeg, Cornelia A

    2012-10-31

    The purpose of this study was to characterize the cell surface proteome of native compared to cultured equine retinal pigment epithelium (RPE) cells. The RPE plays an essential role in visual function and represents the outer blood-retinal barrier. We are investigating immunopathomechanisms of equine recurrent uveitis, an autoimmune inflammatory disease in horses leading to breakdown of the outer blood-retinal barrier and influx of autoreactive T-cells into affected horses' vitrei. Cell surface proteins of native and cultured RPE cells from eye-healthy horses were captured by biotinylation, analyzed by high resolution mass spectrometry coupled to liquid chromatography (LC MS/MS), and the most interesting candidates were validated by PCR, immunoblotting and immunocytochemistry. A total of 112 proteins were identified, of which 84% were cell surface membrane proteins. Twenty-three of these proteins were concurrently expressed by both cell states, 28 proteins exclusively by native RPE cells. Among the latter were two RPE markers with highly specialized RPE functions: cellular retinaldehyde-binding protein (CRALBP) and retinal pigment epithelium-specific protein 65kDa (RPE65). Furthermore, 61 proteins were only expressed by cultured RPE cells and absent in native cells. As we believe that initiating events, leading to the breakdown of the outer blood-retinal barrier, take place at the cell surface of RPE cells as a particularly exposed barrier structure, this differential characterization of cell surface proteomes of native and cultured equine RPE cells is a prerequisite for future studies.

  14. Effect of heated naringenin on immunomodulatory properties and cellular antioxidant activity.

    PubMed

    Maatouk, Mouna; Elgueder, Dorra; Mustapha, Nadia; Chaaban, Hind; Bzéouich, Imen Mokdad; Loannou, Irina; Kilani, Soumaya; Ghoul, Mohamed; Ghedira, Kamel; Chekir-Ghedira, Leila

    2016-11-01

    Naringenin is one of the most popular flavonoids derived from citrus. It has been reported to be an effective anti-inflammatory compound. Citrus fruit may be used raw, cooked, stewed, or boiled. The present study was conducted to investigate the effect of thermal processes on naringenin in its immunomodulatory and cellular antioxidant activities. The effects of flavonoids on B and T cell proliferation were assessed on splenocytes stimulated or not with mitogens. However, their effects on cytotoxic T lymphocyte (CTL) and natural killer (NK) activities were assessed in splenocytes co-incubated with target cells. The amount of nitric oxide production and the lysosomal enzyme activity were evaluated in vitro on mouse peritoneal macrophages. Cellular antioxidant activity in splenocytes and macrophages was determined by measuring the fluorescence of the dichlorofluorescin (DCF). Our findings revealed that naringenin induces B cell proliferation and enhances NK activity. The highest concentration of native naringenin exhibits a significant proliferation of T cells, induces CTL activity, and inhibits cellular oxidation in macrophages. Conversely, it was observed that when heat-processed, naringenin improves the cellular antioxidant activity in splenocytes, increases the cytotoxic activity of NK cells, and suppresses the cytotoxicity of T cells. However, heat treatment maintains the anti-inflammatory potency of naringenin.

  15. Ligand-free palladium-mediated site-specific protein labeling inside gram-negative bacterial pathogens.

    PubMed

    Li, Jie; Lin, Shixian; Wang, Jie; Jia, Shang; Yang, Maiyun; Hao, Ziyang; Zhang, Xiaoyu; Chen, Peng R

    2013-05-15

    Palladium, a key transition metal in advancing modern organic synthesis, mediates diverse chemical conversions including many carbon-carbon bond formation reactions between organic compounds. However, expanding palladium chemistry for conjugation of biomolecules such as proteins, particularly within their native cellular context, is still in its infancy. Here we report the site-specific protein labeling inside pathogenic Gram-negative bacterial cells via a ligand-free palladium-mediated cross-coupling reaction. Two rationally designed pyrrolysine analogues bearing an aliphatic alkyne or an iodophenyl handle were first encoded in different enteric bacteria, which offered two facial handles for palladium-mediated Sonogashira coupling reaction on proteins within these pathogens. A GFP-based bioorthogonal reaction screening system was then developed, allowing evaluation of both the efficiency and the biocompatibilty of various palladium reagents in promoting protein-small molecule conjugation. The identified simple compound-Pd(NO3)2 exhibited high efficiency and biocompatibility for site-specific labeling of proteins in vitro and inside living E. coli cells. This Pd-mediated protein coupling method was further utilized to label and visualize a Type-III Secretion (T3S) toxin-OspF in Shigella cells. Our strategy may be generally applicable for imaging and tracking various virulence proteins within Gram-negative bacterial pathogens.

  16. Alpha-crystallin-type heat shock proteins: socializing minichaperones in the context of a multichaperone network.

    PubMed

    Narberhaus, Franz

    2002-03-01

    Alpha-crystallins were originally recognized as proteins contributing to the transparency of the mammalian eye lens. Subsequently, they have been found in many, but not all, members of the Archaea, Bacteria, and Eucarya. Most members of the diverse alpha-crystallin family have four common structural and functional features: (i) a small monomeric molecular mass between 12 and 43 kDa; (ii) the formation of large oligomeric complexes; (iii) the presence of a moderately conserved central region, the so-called alpha-crystallin domain; and (iv) molecular chaperone activity. Since alpha-crystallins are induced by a temperature upshift in many organisms, they are often referred to as small heat shock proteins (sHsps) or, more accurately, alpha-Hsps. Alpha-crystallins are integrated into a highly flexible and synergistic multichaperone network evolved to secure protein quality control in the cell. Their chaperone activity is limited to the binding of unfolding intermediates in order to protect them from irreversible aggregation. Productive release and refolding of captured proteins into the native state requires close cooperation with other cellular chaperones. In addition, alpha-Hsps seem to play an important role in membrane stabilization. The review compiles information on the abundance, sequence conservation, regulation, structure, and function of alpha-Hsps with an emphasis on the microbial members of this chaperone family.

  17. Nonmuscle myosin is regulated during smooth muscle contraction.

    PubMed

    Yuen, Samantha L; Ogut, Ozgur; Brozovich, Frank V

    2009-07-01

    The participation of nonmuscle myosin in force maintenance is controversial. Furthermore, its regulation is difficult to examine in a cellular context, as the light chains of smooth muscle and nonmuscle myosin comigrate under native and denaturing electrophoresis techniques. Therefore, the regulatory light chains of smooth muscle myosin (SM-RLC) and nonmuscle myosin (NM-RLC) were purified, and these proteins were resolved by isoelectric focusing. Using this method, intact mouse aortic smooth muscle homogenates demonstrated four distinct RLC isoelectric variants. These spots were identified as phosphorylated NM-RLC (most acidic), nonphosphorylated NM-RLC, phosphorylated SM-RLC, and nonphosphorylated SM-RLC (most basic). During smooth muscle activation, NM-RLC phosphorylation increased. During depolarization, the increase in NM-RLC phosphorylation was unaffected by inhibition of either Rho kinase or PKC. However, inhibition of Rho kinase blocked the angiotensin II-induced increase in NM-RLC phosphorylation. Additionally, force for angiotensin II stimulation of aortic smooth muscle from heterozygous nonmuscle myosin IIB knockout mice was significantly less than that of wild-type littermates, suggesting that, in smooth muscle, activation of nonmuscle myosin is important for force maintenance. The data also demonstrate that, in smooth muscle, the activation of nonmuscle myosin is regulated by Ca(2+)-calmodulin-activated myosin light chain kinase during depolarization and a Rho kinase-dependent pathway during agonist stimulation.

  18. α-Crystallin-Type Heat Shock Proteins: Socializing Minichaperones in the Context of a Multichaperone Network

    PubMed Central

    Narberhaus, Franz

    2002-01-01

    α-Crystallins were originally recognized as proteins contributing to the transparency of the mammalian eye lens. Subsequently, they have been found in many, but not all, members of the Archaea, Bacteria, and Eucarya. Most members of the diverse α-crystallin family have four common structural and functional features: (i) a small monomeric molecular mass between 12 and 43 kDa; (ii) the formation of large oligomeric complexes; (iii) the presence of a moderately conserved central region, the so-called α-crystallin domain; and (iv) molecular chaperone activity. Since α-crystallins are induced by a temperature upshift in many organisms, they are often referred to as small heat shock proteins (sHsps) or, more accurately, α-Hsps. α-Crystallins are integrated into a highly flexible and synergistic multichaperone network evolved to secure protein quality control in the cell. Their chaperone activity is limited to the binding of unfolding intermediates in order to protect them from irreversible aggregation. Productive release and refolding of captured proteins into the native state requires close cooperation with other cellular chaperones. In addition, α-Hsps seem to play an important role in membrane stabilization. The review compiles information on the abundance, sequence conservation, regulation, structure, and function of α-Hsps with an emphasis on the microbial members of this chaperone family. PMID:11875128

  19. Modeling the long-term effects of introduced herbivores on the spread of an invasive tree

    USGS Publications Warehouse

    Zhang, Bo; DeAngelis, Donald L.; Rayamajhi, Min B.; Botkin, Daniel B.

    2017-01-01

    ContextMelaleuca quinquenervia (Cav.) Blake (hereafter melaleuca) is an invasive tree from Australia that has spread over the freshwater ecosystems of southern Florida, displacing native vegetation, thus threatening native biodiversity. Suppression of melaleuca appears to be progressing through the introduction of insect species, the weevil, Oxiops vitiosa, and the psyllid, Boreioglycaspis melaleucae.ObjectiveTo improve understanding of the possible effects of herbivory on the landscape dynamics of melaleuca in native southern Florida plant communities.MethodsWe projected likely future changes in plant communities using the individual based modeling platform, JABOWA-II, by simulating successional processes occurring in two types of southern Florida habitat, cypress swamp and bay swamp, occupied by native species and melaleuca, with the impact of insect herbivores.ResultsComputer simulations show melaleuca invasion leads to decreases in density and basal area of native species, but herbivory would effectively control melaleuca to low levels, resulting in a recovery of native species. When herbivory was modeled on pure melaleuca stands, it was more effective in stands with initially larger-sized melaleuca. Although the simulated herbivory did not eliminate melaleuca, it decreased its presence dramatically in all cases, supporting the long-term effectiveness of herbivory in controlling melaleuca invasion.ConclusionsThe results provide three conclusions relevant to management: (1) The introduction of insect herbivory that has been applied to melaleuca appears sufficient to suppress melaleuca over the long term, (2) dominant native species may recover in about 50 years, and (3) regrowth of native species will further suppress melaleuca through competition.

  20. Combining blue native polyacrylamide gel electrophoresis with liquid chromatography tandem mass spectrometry as an effective strategy for analyzing potential membrane protein complexes of Mycobacterium bovis bacillus Calmette-Guérin

    PubMed Central

    2011-01-01

    Background Tuberculosis is an infectious bacterial disease in humans caused primarily by Mycobacterium tuberculosis, and infects one-third of the world's total population. Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine has been widely used to prevent tuberculosis worldwide since 1921. Membrane proteins play important roles in various cellular processes, and the protein-protein interactions involved in these processes may provide further information about molecular organization and cellular pathways. However, membrane proteins are notoriously under-represented by traditional two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and little is known about mycobacterial membrane and membrane-associated protein complexes. Here we investigated M. bovis BCG by an alternative proteomic strategy coupling blue native PAGE to liquid chromatography tandem mass spectrometry (LC-MS/MS) to characterize potential protein-protein interactions in membrane fractions. Results Using this approach, we analyzed native molecular composition of protein complexes in BCG membrane fractions. As a result, 40 proteins (including 12 integral membrane proteins), which were organized in 9 different gel bands, were unambiguous identified. The proteins identified have been experimentally confirmed using 2-D SDS PAGE. We identified MmpL8 and four neighboring proteins that were involved in lipid transport complexes, and all subunits of ATP synthase complex in their monomeric states. Two phenolpthiocerol synthases and three arabinosyltransferases belonging to individual operons were obtained in different gel bands. Furthermore, two giant multifunctional enzymes, Pks7 and Pks8, and four mycobacterial Hsp family members were determined. Additionally, seven ribosomal proteins involved in polyribosome complex and two subunits of the succinate dehydrogenase complex were also found. Notablely, some proteins with high hydrophobicity or multiple transmembrane helixes were identified well in our work. Conclusions In this study, we utilized LC-MS/MS in combination with blue native PAGE to characterize modular components of multiprotein complexes in BCG membrane fractions. The results demonstrated that the proteomic strategy was a reliable and reproducible tool for analysis of BCG multiprotein complexes. The identification in our study may provide some evidence for further study of BCG protein interaction. PMID:21241518

  1. Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl−‐dependent and independent mechanisms

    PubMed Central

    Penton, David; Czogalla, Jan; Wengi, Agnieszka; Himmerkus, Nina; Loffing‐Cueni, Dominique; Carrel, Monique; Rajaram, Renuga Devi; Staub, Olivier; Bleich, Markus; Schweda, Frank

    2016-01-01

    Key points High dietary potassium (K+) intake dephosphorylates and inactivates the NaCl cotransporter (NCC) in the renal distal convoluted tubule (DCT).Using several ex vivo models, we show that physiological changes in extracellular K+, similar to those occurring after a K+ rich diet, are sufficient to promote a very rapid dephosphorylation of NCC in native DCT cells.Although the increase of NCC phosphorylation upon decreased extracellular K+ appears to depend on cellular Cl− fluxes, the rapid NCC dephosphorylation in response to increased extracellular K+ is not Cl−‐dependent.The Cl−‐dependent pathway involves the SPAK/OSR1 kinases, whereas the Cl− independent pathway may include additional signalling cascades. Abstract A high dietary potassium (K+) intake causes a rapid dephosphorylation, and hence inactivation, of the thiazide‐sensitive NaCl cotransporter (NCC) in the renal distal convoluted tubule (DCT). Based on experiments in heterologous expression systems, it was proposed that changes in extracellular K+ concentration ([K+]ex) modulate NCC phosphorylation via a Cl−‐dependent modulation of the with no lysine (K) kinases (WNK)‐STE20/SPS‐1‐44 related proline‐alanine‐rich protein kinase (SPAK)/oxidative stress‐related kinase (OSR1) kinase pathway. We used the isolated perfused mouse kidney technique and ex vivo preparations of mouse kidney slices to test the physiological relevance of this model on native DCT. We demonstrate that NCC phosphorylation inversely correlates with [K+]ex, with the most prominent effects occurring around physiological plasma [K+]. Cellular Cl− conductances and the kinases SPAK/OSR1 are involved in the phosphorylation of NCC under low [K+]ex. However, NCC dephosphorylation triggered by high [K+]ex is neither blocked by removing extracellular Cl−, nor by the Cl− channel blocker 4,4′‐diisothiocyano‐2,2′‐stilbenedisulphonic acid. The response to [K+]ex on a low extracellular chloride concentration is also independent of significant changes in SPAK/OSR1 phosphorylation. Thus, in the native DCT, [K+]ex directly and rapidly controls NCC phosphorylation by Cl−‐dependent and independent pathways that involve the kinases SPAK/OSR1 and a yet unidentified additional signalling mechanism. PMID:27457700

  2. Multidimensional immunolabeling and 4D time-lapse imaging of vital ex vivo lung tissue

    PubMed Central

    Vierkotten, Sarah; Lindner, Michael; Königshoff, Melanie; Eickelberg, Oliver

    2015-01-01

    During the last decades, the study of cell behavior was largely accomplished in uncoated or extracellular matrix (ECM)-coated plastic dishes. To date, considerable cell biological efforts have tried to model in vitro the natural microenvironment found in vivo. For the lung, explants cultured ex vivo as lung tissue cultures (LTCs) provide a three-dimensional (3D) tissue model containing all cells in their natural microenvironment. Techniques for assessing the dynamic live interaction between ECM and cellular tissue components, however, are still missing. Here, we describe specific multidimensional immunolabeling of living 3D-LTCs, derived from healthy and fibrotic mouse lungs, as well as patient-derived 3D-LTCs, and concomitant real-time four-dimensional multichannel imaging thereof. This approach allowed the evaluation of dynamic interactions between mesenchymal cells and macrophages with their ECM. Furthermore, fibroblasts transiently expressing focal adhesions markers incorporated into the 3D-LTCs, paving new ways for studying the dynamic interaction between cellular adhesions and their natural-derived ECM. A novel protein transfer technology (FuseIt/Ibidi) shuttled fluorescently labeled α-smooth muscle actin antibodies into the native cells of living 3D-LTCs, enabling live monitoring of α-smooth muscle actin-positive stress fibers in native tissue myofibroblasts residing in fibrotic lesions of 3D-LTCs. Finally, this technique can be applied to healthy and diseased human lung tissue, as well as to adherent cells in conventional two-dimensional cell culture. This novel method will provide valuable new insights into the dynamics of ECM (patho)biology, studying in detail the interaction between ECM and cellular tissue components in their natural microenvironment. PMID:26092995

  3. A Major Binding Protein for Leukemia Inhibitory Factor in Normal Mouse Serum: Identification as a Soluble Form of the Cellular Receptor

    NASA Astrophysics Data System (ADS)

    Layton, Meredith J.; Cross, Bronwyn A.; Metcalf, Donald; Ward, Larry D.; Simpson, Richard J.; Nicola, Nicos A.

    1992-09-01

    A protein that specifically binds leukemia inhibitory factor (LIF) has been isolated from normal mouse serum by using four successive fractionation steps: chromatography on a LIF affinity matrix, anion-exchange chromatography, size-exclusion chromatography, and preparative native gel electrophoresis. The purified LIF-binding protein (LBP) is a glycoprotein with an apparent molecular mass of 90 kDa that specifically binds 125I-labeled murine LIF with an affinity comparable to that of the low-affinity cellular LIF receptor (K_d = 600 pM). N-terminal sequencing has identified this protein as a soluble truncated form of the α chain of the cellular LIF receptor. LBP is present in normal mouse serum at high levels (1 μg/ml) and these levels are elevated in pregnant mice and reduced in neonatal mice. Since normal serum concentrations of LBP can block the biological actions of LIF in culture, LBP may serve as an inhibitor of the systemic effects of locally produced LIF.

  4. Biomolecular interactions modulate macromolecular structure and dynamics in atomistic model of a bacterial cytoplasm

    PubMed Central

    Yu, Isseki; Mori, Takaharu; Ando, Tadashi; Harada, Ryuhei; Jung, Jaewoon; Sugita, Yuji; Feig, Michael

    2016-01-01

    Biological macromolecules function in highly crowded cellular environments. The structure and dynamics of proteins and nucleic acids are well characterized in vitro, but in vivo crowding effects remain unclear. Using molecular dynamics simulations of a comprehensive atomistic model cytoplasm we found that protein-protein interactions may destabilize native protein structures, whereas metabolite interactions may induce more compact states due to electrostatic screening. Protein-protein interactions also resulted in significant variations in reduced macromolecular diffusion under crowded conditions, while metabolites exhibited significant two-dimensional surface diffusion and altered protein-ligand binding that may reduce the effective concentration of metabolites and ligands in vivo. Metabolic enzymes showed weak non-specific association in cellular environments attributed to solvation and entropic effects. These effects are expected to have broad implications for the in vivo functioning of biomolecules. This work is a first step towards physically realistic in silico whole-cell models that connect molecular with cellular biology. DOI: http://dx.doi.org/10.7554/eLife.19274.001 PMID:27801646

  5. Axl as a mediator of cellular growth and survival

    PubMed Central

    Axelrod, Haley; Pienta, Kenneth J.

    2014-01-01

    The control of cellular growth and proliferation is key to the maintenance of homeostasis. Survival, proliferation, and arrest are regulated, in part, by Growth Arrest Specific 6 (Gas6) through binding to members of the TAM receptor tyrosine kinase family. Activation of the TAM receptors leads to downstream signaling through common kinases, but the exact mechanism within each cellular context varies and remains to be completely elucidated. Deregulation of the TAM family, due to its central role in mediating cellular proliferation, has been implicated in multiple diseases. Axl was cloned as the first TAM receptor in a search for genes involved in the progression of chronic to acute-phase leukemia, and has since been established as playing a critical role in the progression of cancer. The oncogenic nature of Axl is demonstrated through its activation of signaling pathways involved in proliferation, migration, inhibition of apoptosis, and therapeutic resistance. Despite its recent discovery, significant progress has been made in the development of effective clinical therapeutics targeting Axl. In order to accurately define the role of Axl in normal and diseased processes, it must be analyzed in a cell type-specific context. PMID:25344858

  6. Warmth of the Welcome: Attitudes toward Immigrants and Immigration Policy

    PubMed Central

    Fussell, Elizabeth

    2015-01-01

    Natives' attitudes toward immigrants and immigration policy are important factors in the context of reception of immigrants since they contribute to a warm or chilly welcome, which potentially shapes immigrant and ethnic identities and inter-group relations. Public opinion polls show a recent “warming” of Americans' traditional ambivalence about immigration. Empirical research on attitudes toward immigrants and racial groups formed by recent waves of immigrants resonate with the dynamic nature of Blumer's (1958) theory of prejudice as a sense of relative group position. To better understand this dynamism, research that intentionally contrasts study sites on conflict and contact conditions and the presence of absence of symbolic politics, as well as research with different native-born racial and ethnic groups, would reveal a broader range of natives' attitude formation processes and the role they play in immigrant reception. PMID:26966338

  7. Cell-based therapeutics: the next pillar of medicine.

    PubMed

    Fischbach, Michael A; Bluestone, Jeffrey A; Lim, Wendell A

    2013-04-03

    Two decades ago, the pharmaceutical industry-long dominated by small-molecule drugs-was revolutionized by the the advent of biologics. Today, biomedicine sits on the cusp of a new revolution: the use of microbial and human cells as versatile therapeutic engines. Here, we discuss the promise of this "third pillar" of therapeutics in the context of current scientific, regulatory, economic, and perceptual challenges. History suggests that the advent of cellular medicines will require the development of a foundational cellular engineering science that provides a systematic framework for safely and predictably altering and regulating cellular behaviors.

  8. Competition for Shared Resources in the Cellular Chassis: Impact on Synthetic Circuits

    DTIC Science & Technology

    2013-11-01

    glyceraldehyde dehydrogenase from E. coli and it is very abundant in the bacterial cytoplasm. The control MBP-dRFP does not display an effect on GFP ...discover how key parameters control the extent of coupling we constructed an analytical model that predicts how the concentration of one protein ( GFP ...SECURITY CLASSIFICATION OF: Protein overexpression leads to growth inhibition and decreased expression of native proteins. This effect is mostly due

  9. Comparative Activity-Based Flavin-Dependent Oxidase Profiling.

    PubMed

    Krysiak, Joanna; Breinbauer, Rolf

    2017-01-01

    Activity-based protein profiling (ABPP) has become a powerful chemoproteomic technology allowing for the dissection of complex ligand-protein interactions in their native cellular environment. One of the biggest challenges for ABPP is the extension of the proteome coverage. In this chapter a new ABPP strategy dedicated to monoamine oxidases (MAO) is presented. These enzymes are representative examples of flavin-dependent oxidases, playing a crucial role in the regulation of nervous system signaling.

  10. Foreign Languages Sound Fast: Evidence from Implicit Rate Normalization.

    PubMed

    Bosker, Hans Rutger; Reinisch, Eva

    2017-01-01

    Anecdotal evidence suggests that unfamiliar languages sound faster than one's native language. Empirical evidence for this impression has, so far, come from explicit rate judgments. The aim of the present study was to test whether such perceived rate differences between native and foreign languages (FLs) have effects on implicit speech processing. Our measure of implicit rate perception was "normalization for speech rate": an ambiguous vowel between short /a/ and long /a:/ is interpreted as /a:/ following a fast but as /a/ following a slow carrier sentence. That is, listeners did not judge speech rate itself; instead, they categorized ambiguous vowels whose perception was implicitly affected by the rate of the context. We asked whether a bias towards long /a:/ might be observed when the context is not actually faster but simply spoken in a FL. A fully symmetrical experimental design was used: Dutch and German participants listened to rate matched (fast and slow) sentences in both languages spoken by the same bilingual speaker. Sentences were followed by non-words that contained vowels from an /a-a:/ duration continuum. Results from Experiments 1 and 2 showed a consistent effect of rate normalization for both listener groups. Moreover, for German listeners, across the two experiments, foreign sentences triggered more /a:/ responses than (rate matched) native sentences, suggesting that foreign sentences were indeed perceived as faster. Moreover, this FL effect was modulated by participants' ability to understand the FL: those participants that scored higher on a FL translation task showed less of a FL effect. However, opposite effects were found for the Dutch listeners. For them, their native rather than the FL induced more /a:/ responses. Nevertheless, this reversed effect could be reduced when additional spectral properties of the context were controlled for. Experiment 3, using explicit rate judgments, replicated the effect for German but not Dutch listeners. We therefore conclude that the subjective impression that FLs sound fast may have an effect on implicit speech processing, with implications for how language learners perceive spoken segments in a FL.

  11. RBFOX2 protein domains and cellular activities.

    PubMed

    Arya, Anurada D; Wilson, David I; Baralle, Diana; Raponi, Michaela

    2014-08-01

    RBFOX2 (RNA-binding protein, Fox-1 homologue 2)/RBM9 (RNA-binding-motif protein 9)/RTA (repressor of tamoxifen action)/HNRBP2 (hexaribonucleotide-binding protein 2) encodes an RNA-binding protein involved in tissue specific alternative splicing regulation and steroid receptors transcriptional activity. Its ability to regulate specific splicing profiles depending on context has been related to different expression levels of the RBFOX2 protein itself and that of other splicing regulatory proteins involved in the shared modulation of specific genes splicing. However, this cannot be the sole explanation as to why RBFOX2 plays a widespread role in numerous cellular mechanisms from development to cell survival dependent on cell/tissue type. RBFOX2 isoforms with altered protein domains exist. In the present article, we describe the main RBFOX2 protein domains, their importance in the context of splicing and transcriptional regulation and we propose that RBFOX2 isoform distribution may play a fundamental role in RBFOX2-specific cellular effects.

  12. Chitosan based hydrogels: characteristics and pharmaceutical applications

    PubMed Central

    Ahmadi, F.; Oveisi, Z.; Samani, S. Mohammadi; Amoozgar, Z.

    2015-01-01

    Hydrogel scaffolds serve as semi synthetic or synthetic extra cellular matrix to provide an amenable environment for cellular adherence and cellular remodeling in three dimensional structures mimicking that of natural cellular environment. Additionally, hydrogels have the capacity to carry small molecule drugs and/or proteins, growth factors and other necessary components for cell growth and differentiation. In the context of drug delivery, hydrogels can be utilized to localize drugs, increase drugs concentration at the site of action and consequently reduce off-targeted side effects. The current review aims to describe and classify hydrogels and their methods of production. The main highlight is chitosan-based hydrogels as biocompatible and medically relevant hydrogels for drug delivery. PMID:26430453

  13. From hatching to dispatching: the multiple cellular roles of the Hsp70 molecular chaperone machinery.

    PubMed

    Meimaridou, Eirini; Gooljar, Sakina B; Chapple, J Paul

    2009-01-01

    Molecular chaperones are best recognized for their roles in de novo protein folding and the cellular response to stress. However, many molecular chaperones, and in particular the Hsp70 chaperone machinery, have multiple diverse cellular functions. At the molecular level, chaperones are mediators of protein conformational change. To facilitate conformational change of client/substrate proteins, in manifold contexts, chaperone power must be closely regulated and harnessed to specific cellular locales--this is controlled by cochaperones. This review considers specialized functions of the Hsp70 chaperone machinery mediated by its cochaperones. We focus on vesicular trafficking, protein degradation and a potential role in G protein-coupled receptor processing.

  14. "The Poison That Ruined the Nation": Native American Men-Alcohol, Identity, and Traditional Healing.

    PubMed

    Matamonasa-Bennett, Arieahn

    2017-07-01

    Alcoholism and destructive drinking patterns are serious social problems in many Native American reservation and urban communities. This qualitative study of men from a single Great Lakes reservation community examined the social, cultural, and psychological aspects of their alcohol problems through their life stories. The men were in various stages of recovery and sobriety, and data collection consisted of open-ended interviews and analysis utilizing principles and techniques from grounded theory and ethnographic content analysis. Alcoholism and other serious social problems facing Native American communities need to be understood in the sociocultural and historical contexts of colonization and historical grief and trauma. This study suggests that for Native American men, there are culturally specific perspectives on alcohol that have important implications for prevention and treatment of alcohol abuse. The participants' narratives provided insight into the ways reconnecting with traditional cultural values (retraditionalization) helped them achieve sobriety. For these men, alcohol was highly symbolic of colonization as well as a protest to it. Alcohol was a means for affirming "Indian" identity and sobriety a means for reaffirming traditional tribal identity. Their narratives suggested the ways in which elements of traditional cultural values and practices facilitate healing in syncretic models and Nativized treatment. Understanding the ways in which specific Native cultural groups perceive their problems with drinking and sobriety can create more culturally congruent, culturally sensitive, and effective treatment approaches and inform future research.

  15. Histone modifications controlling native and induced neural stem cell identity.

    PubMed

    Broccoli, Vania; Colasante, Gaia; Sessa, Alessandro; Rubio, Alicia

    2015-10-01

    During development, neural progenitor cells (NPCs) that are capable of self-renewing maintain a proliferative cellular pool while generating all differentiated neural cell components. Although the genetic network of transcription factors (TFs) required for neural specification has been well characterized, the unique set of histone modifications that accompanies this process has only recently started to be investigated. In vitro neural differentiation of pluripotent stem cells is emerging as a powerful system to examine epigenetic programs. Deciphering the histone code and how it shapes the chromatin environment will reveal the intimate link between epigenetic changes and mechanisms for neural fate determination in the developing nervous system. Furthermore, it will offer a molecular framework for a stringent comparison between native and induced neural stem cells (iNSCs) generated by direct neural cell conversion. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Protein quality control: the who’s who, the where’s and therapeutic escapes

    PubMed Central

    Yam, Gary Hin-Fai; Fan, Jingyu; Hirano, Kiyoko; Gaplovska-Kysela, Katarina; Le Fourn, Valerie; Guhl, Bruno; Santimaria, Roger; Torossi, Tania; Ziak, Martin

    2007-01-01

    In cells the quality of newly synthesized proteins is monitored in regard to proper folding and correct assembly in the early secretory pathway, the cytosol and the nucleoplasm. Proteins recognized as non-native in the ER will be removed and degraded by a process termed ERAD. ERAD of aberrant proteins is accompanied by various changes of cellular organelles and results in protein folding diseases. This review focuses on how the immunocytochemical labeling and electron microscopic analyses have helped to disclose the in situ subcellular distribution pattern of some of the key machinery proteins of the cellular protein quality control, the organelle changes due to the presence of misfolded proteins, and the efficiency of synthetic chaperones to rescue disease-causing trafficking defects of aberrant proteins. PMID:18075753

  17. A tissue engineering approach to anterior cruciate ligament regeneration using novel shaped capillary channel polymer fibers

    NASA Astrophysics Data System (ADS)

    Sinclair, Kristofer D.

    2009-12-01

    Ruptures of the anterior cruciate ligament (ACL) are the most frequent of injuries to the knee due to its role in preventing anterior translation of the tibia. It is estimated that as many as 200,000 Americans per year will suffer from a ruptured ACL, resulting in management costs on the order of 5 billion dollars. Without treatment these patients are unable to return to normal activity, as a consequence of the joint instability found within the ACL deficient knee. Over the last thirty years, a variety of non-degradable, synthetic fibers have been evaluated for their use in ACL reconstruction; however, a widely accepted prosthesis has been unattainable due to differences in mechanical properties of the synthetic graft relative to the native tissue. Tissue engineering is an interdisciplinary field charged with the task of developing therapeutic solutions for tissue and organ failure by enhancing the natural wound healing process through the use of cellular transplants, biomaterials, and the delivery of bioactive molecules. The capillary channel polymer (CC-P) fibers used in this research were fabricated by melt extrusion from polyethylene terephthalate and polybutylene terephthalate. These fibers possess aligned micrometer scale surface channels that may serve as physical templates for tissue growth and regeneration. This inherent surface topography offers a unique and industrially viable approach for cellular contact guidance on three dimensional constructs. In this fundamental research the ability of these fiber channels to support the adhesion, alignment, and organization of fibroblasts was demonstrated and found to be superior to round fiber controls. The results demonstrated greater uniformity of seeding and accelerated formation of multi-layered three-dimensional biomass for the CC-P fibers relative to those with a circular cross-section. Furthermore, the CC-P geometry induced nuclear elongation consistent with that observed in native ACL tissue. Through the application of uniaxial cyclic strain the mechanical properties of the cell seeded CC-P fiber scaffold systems were shown to improve via the induction of increased cellular proliferation and extracellular matrix synthesis. Finally, unlike many studies examining the effects of cyclic strain on cellular behavior, the CC-P fiber geometry displayed the ability to maintain cellular alignment in the presence of an applied uniaxial cyclic strain.

  18. Categorical Perception of Affective and Linguistic Facial Expressions

    ERIC Educational Resources Information Center

    McCullough, Stephen; Emmorey, Karen

    2009-01-01

    Two experiments investigated categorical perception (CP) effects for affective facial expressions and linguistic facial expressions from American Sign Language (ASL) for Deaf native signers and hearing non-signers. Facial expressions were presented in isolation (Experiment 1) or in an ASL verb context (Experiment 2). Participants performed ABX…

  19. Differential Antibody Responses to Conserved HIV-1 Neutralizing Epitopes in the Context of Multivalent Scaffolds and Native-Like gp140 Trimers.

    PubMed

    Morris, Charles D; Azadnia, Parisa; de Val, Natalia; Vora, Nemil; Honda, Andrew; Giang, Erick; Saye-Francisco, Karen; Cheng, Yushao; Lin, Xiaohe; Mann, Colin J; Tang, Jeffrey; Sok, Devin; Burton, Dennis R; Law, Mansun; Ward, Andrew B; He, Linling; Zhu, Jiang

    2017-02-28

    Broadly neutralizing antibodies (bNAbs) have provided valuable insights into the humoral immune response to HIV-1. While rationally designed epitope scaffolds and well-folded gp140 trimers have been proposed as vaccine antigens, a comparative understanding of their antibody responses has not yet been established. In this study, we probed antibody responses to the N332 supersite and the membrane-proximal external region (MPER) in the context of heterologous protein scaffolds and native-like gp140 trimers. Ferritin nanoparticles and fragment crystallizable (Fc) regions were utilized as multivalent carriers to display scaffold antigens with grafted N332 and MPER epitopes, respectively. Trimeric scaffolds were also identified to stabilize the MPER-containing BG505 gp140.681 trimer in a native-like conformation. Following structural and antigenic evaluation, a subset of scaffold and trimer antigens was selected for immunization in BALB/c mice. Serum binding revealed distinct patterns of antibody responses to these two bNAb targets presented in different structural contexts. For example, the N332 nanoparticles elicited glycan epitope-specific antibody responses that could also recognize the native trimer, while a scaffolded BG505 gp140.681 trimer generated a stronger and more rapid antibody response to the trimer apex than its parent gp140.664 trimer. Furthermore, next-generation sequencing (NGS) of mouse splenic B cells revealed expansion of antibody lineages with long heavy-chain complementarity-determining region 3 (HCDR3) loops upon activation by MPER scaffolds, in contrast to the steady repertoires primed by N332 nanoparticles and a soluble gp140.664 trimer. These findings will facilitate the future development of a coherent vaccination strategy that combines both epitope-focused and trimer-based approaches. IMPORTANCE Both epitope-focused and trimer-based strategies are currently being explored in HIV-1 vaccine development, which aims to elicit broadly neutralizing antibodies (bNAbs) targeting conserved epitopes on the viral envelope (Env). However, little is known about the differences in antibody response to these bNAb targets presented by foreign scaffolds and native Env. In this study, a systematic effort was undertaken to design multivalent epitope scaffolds and soluble gp140.681 trimers with a complete antigenic surface, and to comparatively analyze the antibody responses elicited by these antigens to the N332 supersite and MPER in a mouse model. This study will inform both epitope-focused and trimer-based vaccine design and will facilitate integration of the two vaccine strategies. Copyright © 2017 Morris et al.

  20. An invasive foundation species enhances multifunctionality in a coastal ecosystem.

    PubMed

    Ramus, Aaron P; Silliman, Brian R; Thomsen, Mads S; Long, Zachary T

    2017-08-08

    While invasive species often threaten biodiversity and human well-being, their potential to enhance functioning by offsetting the loss of native habitat has rarely been considered. We manipulated the abundance of the nonnative, habitat-forming seaweed Gracilaria vermiculophylla in large plots (25 m 2 ) on southeastern US intertidal landscapes to assess impacts on multiple ecosystem functions underlying coastal ecosystem services. We document that in the absence of native habitat formers, this invasion has an overall positive, density-dependent impact across a diverse set of ecosystem processes (e.g., abundance and richness of nursery taxa, flow attenuation). Manipulation of invader abundance revealed both thresholds and saturations in the provisioning of ecosystem functions. Taken together, these findings call into question the focus of traditional invasion research and management that assumes negative effects of nonnatives, and emphasize the need to consider context-dependence and integrative measurements when assessing the impact of an invader, including density dependence, multifunctionality, and the status of native habitat formers. This work supports discussion of the idea that where native foundation species have been lost, invasive habitat formers may be considered as sources of valuable ecosystem functions.

  1. Isolating Fungal Pathogens from a Dynamic Disease Outbreak in a Native Plant Population to Establish Plant-Pathogen Bioassays for the Ecological Model Plant Nicotiana attenuata

    PubMed Central

    Schuck, Stefan; Baldwin, Ian T.

    2014-01-01

    The wild tobacco species Nicotiana attenuata has been intensively used as a model plant to study its interaction with insect herbivores and pollinators in nature, however very little is known about its native pathogen community. We describe a fungal disease outbreak in a native N. attenuata population comprising 873 plants growing in an area of about 1500 m2. The population was divided into 14 subpopulations and disease symptom development in the subpopulations was monitored for 16 days, revealing a waxing and waning of visible disease symptoms with some diseased plants recovering fully. Native fungal N. attenuata pathogens were isolated from diseased plants, characterized genetically, chemotaxonomically and morphologically, revealing several isolates of the ascomycete genera Fusarium and Alternaria, that differed in the type and strength of the disease symptoms they caused in bioassays on either detached leaves or intact soil-grown plants. These isolates and the bioassays will empower the study of N. attenuata-pathogen interactions in a realistic ecological context. PMID:25036191

  2. Effects of age and hearing loss on recognition of unaccented and accented multisyllabic words.

    PubMed

    Gordon-Salant, Sandra; Yeni-Komshian, Grace H; Fitzgibbons, Peter J; Cohen, Julie I

    2015-02-01

    The effects of age and hearing loss on recognition of unaccented and accented words of varying syllable length were investigated. It was hypothesized that with increments in length of syllables, there would be atypical alterations in syllable stress in accented compared to native English, and that these altered stress patterns would be sensitive to auditory temporal processing deficits with aging. Sets of one-, two-, three-, and four-syllable words with the same initial syllable were recorded by one native English and two Spanish-accented talkers. Lists of these words were presented in isolation and in sentence contexts to younger and older normal-hearing listeners and to older hearing-impaired listeners. Hearing loss effects were apparent for unaccented and accented monosyllabic words, whereas age effects were observed for recognition of accented multisyllabic words, consistent with the notion that altered syllable stress patterns with accent are sensitive for revealing effects of age. Older listeners also exhibited lower recognition scores for moderately accented words in sentence contexts than in isolation, suggesting that the added demands on working memory for words in sentence contexts impact recognition of accented speech. The general pattern of results suggests that hearing loss, age, and cognitive factors limit the ability to recognize Spanish-accented speech.

  3. Effects of age and hearing loss on recognition of unaccented and accented multisyllabic words

    PubMed Central

    Gordon-Salant, Sandra; Yeni-Komshian, Grace H.; Fitzgibbons, Peter J.; Cohen, Julie I.

    2015-01-01

    The effects of age and hearing loss on recognition of unaccented and accented words of varying syllable length were investigated. It was hypothesized that with increments in length of syllables, there would be atypical alterations in syllable stress in accented compared to native English, and that these altered stress patterns would be sensitive to auditory temporal processing deficits with aging. Sets of one-, two-, three-, and four-syllable words with the same initial syllable were recorded by one native English and two Spanish-accented talkers. Lists of these words were presented in isolation and in sentence contexts to younger and older normal-hearing listeners and to older hearing-impaired listeners. Hearing loss effects were apparent for unaccented and accented monosyllabic words, whereas age effects were observed for recognition of accented multisyllabic words, consistent with the notion that altered syllable stress patterns with accent are sensitive for revealing effects of age. Older listeners also exhibited lower recognition scores for moderately accented words in sentence contexts than in isolation, suggesting that the added demands on working memory for words in sentence contexts impact recognition of accented speech. The general pattern of results suggests that hearing loss, age, and cognitive factors limit the ability to recognize Spanish-accented speech. PMID:25698021

  4. Immigrant advantage? Substance use among Latin American immigrant and native-born youth in Spain.

    PubMed

    Marsiglia, Flavio Francisco; Kulis, Stephen; Luengo, Maria Angeles; Nieri, Tanya; Villar, Paula

    2008-04-01

    This article reports the results of a descriptive study conducted with middle school and high school age youth residing in northwestern Spain. The main outcome of the study is to advance knowledge about the drug use attitudes and behaviors of immigrants versus native youth in a social context where Latin American immigrants share a common language and a set of core cultural norms with the host society. The research was conducted by a bi-national Spain-US research team as a preliminary study leading to the development of joint culturally appropriate prevention interventions for youth in the northern region of Galicia, Spain. Surveys were administered in Spring 2005 to 817 students in 7th to 10th grades in 10 urban, secondary schools with high immigrant enrollment. The sample included Spanish natives (two-thirds) and Latin American immigrants (one-third), mainly from Colombia, Argentina, and Venezuela. Multiple regression analyses predicted substance use intentions, and a composite variable measuring lifetime and last 30-day frequency and amount of alcohol, cigarette and marijuana use. Controlling for the fact that the immigrant students were generally older and performing less well academically than natives, and for other predictors, Latin American immigrant youth were less at risk than native youth on their intentions to use substances and on their reported actual substance use. In a mediational analysis, most of the key explanatory variables in youth substance use etiology failed to account for the immigrant versus native differences, including a range of risk and protective factors for substance use, substance use norms, strength of ethnic identity, and degree of social integration within native-born social networks. Differential access to drugs mediated the immigrant-native gap in substance use intentions but did not mediate differences in actual substance use.

  5. Overcoming barriers to seedling regeneration during forest restoration on tropical pasture land and the potential value of woody weeds

    PubMed Central

    Elgar, Amelia T.; Freebody, Kylie; Pohlman, Catherine L.; Shoo, Luke P.; Catterall, Carla P.

    2014-01-01

    Combating the legacy of deforestation on tropical biodiversity requires the conversion to forest of large areas of established pasture, where barriers to native plant regeneration include competition with pasture grasses and poor propagule supply (seed availability). In addition, initial woody plants that colonise pasture are often invasive, non-native species whose ecological roles and management in the context of forest regeneration are contested. In a restoration experiment at two 0.64 ha sites we quantified the response of native woody vegetation recruitment to (1) release from competition with introduced pasture grasses, and (2) local facilitation of frugivore-assisted seed dispersal provided by scattered woody plants and artificial bird perches. Herbicide pasture grass suppression during 20 months caused a significant but modest increase in density of native woody seedlings, together with abundant co-recruitment of the prominent non-native pioneer wild tobacco (Solanum mauritianum). Recruitment of native species was further enhanced by local structure in herbicide-treated areas, being consistently greater under live trees and dead non-native shrubs (herbicide-treated) than in open areas, and intermediate under bird perches. Native seedling recruitment comprised 28 species across 0.25 ha sampled but was dominated by two rainforest pioneers (Homalanthus novoguineensis, Polyscias murrayi). These early results are consistent with the expected increase in woody vegetation recruitment in response to release from competitive and dispersive barriers to rainforest regeneration. The findings highlight the need for a pragmatic consideration of the ecological roles of woody weeds and the potential roles of “new forests” more broadly in accelerating succession of humid tropical forest across large areas of retired agricultural land. PMID:24904602

  6. Aromatic residues engineered into the beta-turn nucleation site of ubiquitin lead to a complex folding landscape, non-native side-chain interactions, and kinetic traps.

    PubMed

    Rea, Anita M; Simpson, Emma R; Meldrum, Jill K; Williams, Huw E L; Searle, Mark S

    2008-12-02

    The fast folding of small proteins is likely to be the product of evolutionary pressures that balance the search for native-like contacts in the transition state with the minimum number of stable non-native interactions that could lead to partially folded states prone to aggregation and amyloid formation. We have investigated the effects of non-native interactions on the folding landscape of yeast ubiquitin by introducing aromatic substitutions into the beta-turn region of the N-terminal beta-hairpin, using both the native G-bulged type I turn sequence (TXTGK) as well as an engineered 2:2 XNGK type I' turn sequence. The N-terminal beta-hairpin is a recognized folding nucleation site in ubiquitin. The folding kinetics for wt-Ub (TLTGK) and the type I' turn mutant (TNGK) reveal only a weakly populated intermediate, however, substitution with X = Phe or Trp in either context results in a high propensity to form a stable compact intermediate where the initial U-->I collapse is visible as a distinct kinetic phase. The introduction of Trp into either of the two host turn sequences results in either complex multiphase kinetics with the possibility of parallel folding pathways, or formation of a highly compact I-state stabilized by non-native interactions that must unfold before refolding. Sequence substitutions with aromatic residues within a localized beta-turn capable of forming non-native hydrophobic contacts in both the native state and partially folded states has the undesirable consequence that folding is frustrated by the formation of stable compact intermediates that evolutionary pressures at the sequence level may have largely eliminated.

  7. Immigrant advantage? Substance use among Latin American immigrant and native-born youth in Spain

    PubMed Central

    Marsiglia, Flavio Francisco; Kulis, Stephen; Luengo, Maria Ángeles; Nieri, Tanya; Villar, Paula

    2011-01-01

    This article reports the results of a descriptive study conducted with middle school and high school age youth residing in northwestern Spain. The main outcome of the study is to advance knowledge about the drug use attitudes and behaviors of immigrants versus native youth in a social context where Latin American immigrants share a common language and a set of core cultural norms with the host society. The research was conducted by a bi-national Spain–US research team as a preliminary study leading to the development of joint culturally appropriate prevention interventions for youth in the northern region of Galicia, Spain. Surveys were administered in Spring 2005 to 817 students in 7th to 10th grades in 10 urban, secondary schools with high immigrant enrollment. The sample included Spanish natives (two-thirds) and Latin American immigrants (one-third), mainly from Colombia, Argentina, and Venezuela. Multiple regression analyses predicted substance use intentions, and a composite variable measuring lifetime and last 30-day frequency and amount of alcohol, cigarette and marijuana use. Controlling for the fact that the immigrant students were generally older and performing less well academically than natives, and for other predictors, Latin American immigrant youth were less at risk than native youth on their intentions to use substances and on their reported actual substance use. In a mediational analysis, most of the key explanatory variables in youth substance use etiology failed to account for the immigrant versus native differences, including a range of risk and protective factors for substance use, substance use norms, strength of ethnic identity, and degree of social integration within native-born social networks. Differential access to drugs mediated the immigrant–native gap in substance use intentions but did not mediate differences in actual substance use. PMID:18425712

  8. Network analysis of transcriptomics expands regulatory landscapes in Synechococcus sp. PCC 7002

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

    McClure, Ryan S.; Overall, Christopher C.; McDermott, Jason E.

    Cyanobacterial regulation of gene expression must contend with a genome organization that lacks apparent functional context, as the majority of cellular processes and metabolic pathways are encoded by genes found at disparate locations across the genome. In addition, the fact that coordinated regulation of cyanobacterial cellular machinery takes place with significantly fewer transcription factors, compared to other Eubacteria, suggests the involvement of post-transcriptional mechanisms and regulatory adaptations which are not fully understood. Global transcript abundance from model cyanobacterium Synechococcus sp. PCC 7002 grown under 42 different conditions was analyzed using context-likelihood of relatedness. The resulting 903-gene network, which was organizedmore » into 11 modules, not only allowed classification of cyanobacterial responses to specific environmental variables but provided insight into the transcriptional network topology and led to the expansion of predicted regulons. When used in conjunction with genome sequence, the global transcript abundance allowed identification of putative post-transcriptional changes in expression as well as novel potential targets of both DNA binding proteins and asRNA regulators. The results offer a new perspective into the multi-level regulation that governs cellular adaptations of fast-growing physiologically robust cyanobacterium Synechococcus sp. PCC 7002 to changing environmental variables. It also extends a methodological knowledge-based framework for studying multi-scale regulatory mechanisms that operate in cyanobacteria. Finally, it provides valuable context for integrating systems-level data to enhance evidence-driven genomic annotation, especially in organisms where traditional context analyses cannot be implemented due to lack of operon-based functional organization.« less

  9. Decellularization of Human Internal Mammary Artery: Biomechanical Properties and Histopathological Evaluation.

    PubMed

    Kajbafzadeh, Abdol-Mohammad; Khorramirouz, Reza; Kameli, Seyede Maryam; Hashemi, Javad; Bagheri, Amin

    2017-01-01

    This study undertook to create small-diameter vascular grafts and assess their structure and mechanical properties to withstand arterial implantation. Twenty samples of intact human internal mammary arteries (IMAs) were collected and decellularized using detergent-based methods. To evaluate residual cellular and extracellular matrix (ECM) components, histological analysis was performed. Moreover, collagen typing and ECM structure were analyzed by Picrosirius red and Movat's pentachrome staining. Scanning electron microscopy was also applied to assess microarchitecture of both endothelial and adventitial surfaces of native and decellularized arterial samples. Furthermore, mechanical tests were performed to evaluate the rigidity and suture strength of the arteries. Human IMAs were completely decellularized in all three segments (proximal, middle, and distal). ECM proteins such as collagen and elastic fibers were efficiently preserved and no structural distortion in intima, media, and adventitial surfaces was observed. The parameters of the mechanical tests revealed no significant differences in the mechanical properties of decellularized arteries in comparison to native arteries with considerable strength, suture retention, and stress relaxation (Young's modulus [MPa] = 0.22 ± 0.023 [native] and 0.22 ± 0.015 [acellular]; and suture strength 0.56 ± 0.19 [native] vs. 0.56 ± 0.12 [acellular], respectively). Decellularized IMA represents a potential arterial scaffold as an alternative to autologous grafts for future arterial bypass surgeries. By this technique, microarchitecture and mechanical integrity of decellularized arteries were considerably similar to native arteries. The goal of this study was to introduce an efficient method for complete decellularization of human IMA and evaluate the ECM and biomechanical properties.

  10. Multipotency of skeletal muscle stem cells on their native substrate and the expression of Connexin 43 during adoption of adipogenic and osteogenic fate.

    PubMed

    Elashry, Mohamed I; Heimann, Manuela; Wenisch, Sabine; Patel, Ketan; Arnhold, Stefan

    2017-10-01

    Muscle regeneration is performed by resident muscle stem cells called satellite cells (SC). However they are multipotent, being able to adopt adipogenic and osteogenic fate under the correct stimuli. Since SC behavior can be regulated by the extra-cellular matrix, we examined the robustness of the myogenic programme of SC on their native substrate-the surface of a myofiber. We show that the native substrate supports myogenic differentiation judged by the expression of members of the Myogenic Determination Factor (MRF) family. However SC even on their native substrate can be induced into adopting adipogenic or osteogenic fate. Furthermore conditions that support adipose or bone formation inhibit the proliferation of SC progeny as well as their migration. We show that Connexin43 (Cx43), a gap junction complex protein, is only expressed by activated and not quiescent SC. Furthermore, it is not expressed by SC that are in the process of changing their fate. Lastly we show that intact adult mouse muscle contains numerous cells expressing Cx43 and that the density of these cells seems to be related to capillary density. We suggest the Cx43 expression is localized to angioblasts and is more prominent in oxidative slow muscle compared to glycolytic fast muscle. Crown Copyright © 2017. Published by Elsevier GmbH. All rights reserved.

  11. Internet cigarette sales and Native American sovereignty: political and public health contexts.

    PubMed

    Samuel, Kari A; Ribisl, Kurt M; Williams, Rebecca S

    2012-05-01

    Internet cigarette vendors (ICVs) advertise low prices for tobacco products, subverting public health policy efforts to curtail smoking by raising prices. Many online retailers in the United States claim affiliation with Native American tribes and share in tribal tax-free status. Sales of discounted cigarettes from both online vendors and brick-and-mortar stores have angered non-Native retailers and triggered enforcement actions by state and federal governments in the United States concerned over lost cigarette excise tax revenue. Examination of the history and politics of cigarette sales on reservations and attempts to regulate Internet cigarette sales highlights the potential role for greater use of negotiated intergovernmental agreements to address reservation-based tobacco sales. Our review notes global parallels and explicates history and politics of such regulation in the United States, and offers background for collaborative efforts to regulate tobacco sales and decrease tobacco use.

  12. Microstructural heterogeneity directs micromechanics and mechanobiology in native and engineered fibrocartilage

    NASA Astrophysics Data System (ADS)

    Han, Woojin M.; Heo, Su-Jin; Driscoll, Tristan P.; Delucca, John F.; McLeod, Claire M.; Smith, Lachlan J.; Duncan, Randall L.; Mauck, Robert L.; Elliott, Dawn M.

    2016-04-01

    Treatment strategies to address pathologies of fibrocartilaginous tissue are in part limited by an incomplete understanding of structure-function relationships in these load-bearing tissues. There is therefore a pressing need to develop micro-engineered tissue platforms that can recreate the highly inhomogeneous tissue microstructures that are known to influence mechanotransductive processes in normal and diseased tissue. Here, we report the quantification of proteoglycan-rich microdomains in developing, ageing and diseased fibrocartilaginous tissues, and the impact of these microdomains on endogenous cell responses to physiologic deformation within a native-tissue context. We also developed a method to generate heterogeneous tissue-engineered constructs (hetTECs) with non-fibrous proteoglycan-rich microdomains engineered into the fibrous structure, and show that these hetTECs match the microstructural, micromechanical and mechanobiological benchmarks of native tissue. Our tissue-engineered platform should facilitate the study of the mechanobiology of developing, homeostatic, degenerating and regenerating fibrous tissues.

  13. Microstructural heterogeneity directs micromechanics and mechanobiology in native and engineered fibrocartilage.

    PubMed

    Han, Woojin M; Heo, Su-Jin; Driscoll, Tristan P; Delucca, John F; McLeod, Claire M; Smith, Lachlan J; Duncan, Randall L; Mauck, Robert L; Elliott, Dawn M

    2016-04-01

    Treatment strategies to address pathologies of fibrocartilaginous tissue are in part limited by an incomplete understanding of structure-function relationships in these load-bearing tissues. There is therefore a pressing need to develop micro-engineered tissue platforms that can recreate the highly inhomogeneous tissue microstructures that are known to influence mechanotransductive processes in normal and diseased tissue. Here, we report the quantification of proteoglycan-rich microdomains in developing, ageing and diseased fibrocartilaginous tissues, and the impact of these microdomains on endogenous cell responses to physiologic deformation within a native-tissue context. We also developed a method to generate heterogeneous tissue-engineered constructs (hetTECs) with non-fibrous proteoglycan-rich microdomains engineered into the fibrous structure, and show that these hetTECs match the microstructural, micromechanical and mechanobiological benchmarks of native tissue. Our tissue-engineered platform should facilitate the study of the mechanobiology of developing, homeostatic, degenerating and regenerating fibrous tissues.

  14. New Evidence on the Price Effects of Cigarette Tax Competition.

    PubMed

    Carpenter, Christopher S; Mathes, Michael T

    2016-05-01

    Multiple studies have shown that cigarette taxes are more than fully passed through to cigarette prices and that access to a nearby state with a lower cigarette tax also reduces local cigarette prices. We study two other sources of tax competition: nearby Native American reservations and online sales. Using quarterly data on local cigarette prices from 1976-2003, we show that the opening of a Native American casino within 25 miles of a city center is associated with a $0.016-$0.027 lower per-pack price, while a 50 percentage point increase in internet penetration is associated with a $0.22-$0.25 per-pack price reduction. These effects are not observed for other local prices for which there is no potential tax savings. Our results further our understanding of how tax competition affects local cigarette prices and provide context to studies linking Native American reservations and internet penetration to cigarette smuggling.

  15. Lexical exposure to native language dialects can improve non-native phonetic discrimination.

    PubMed

    Olmstead, Annie J; Viswanathan, Navin

    2018-04-01

    Nonnative phonetic learning is an area of great interest for language researchers, learners, and educators alike. In two studies, we examined whether nonnative phonetic discrimination of Hindi dental and retroflex stops can be improved by exposure to lexical items bearing the critical nonnative stops. We extend the lexical retuning paradigm of Norris, McQueen, and Cutler (Cognitive Psychology, 47, 204-238, 2003) by having naive American English (AE)-speaking participants perform a pretest-training-posttest procedure. They performed an AXB discrimination task with the Hindi retroflex and dental stops before and after transcribing naturally produced words from an Indian English speaker that either contained these tokens or not. Only those participants who heard words with the critical nonnative phones improved in their posttest discrimination. This finding suggests that exposure to nonnative phones in native lexical contexts supports learning of difficult nonnative phonetic discrimination.

  16. Microstructural Heterogeneity in Native and Engineered Fibrocartilage Directs Micromechanics and Mechanobiology

    PubMed Central

    Han, Woojin M; Heo, Su-Jin; Driscoll, Tristan P; Delucca, John F; McLeod, Claire M; Smith, Lachlan J; Duncan, Randall L; Mauck, Robert L; Elliott, Dawn M

    2015-01-01

    Treatment strategies to address pathologies of fibrocartilaginous tissue are in part limited by an incomplete understanding of structure-function relationships in these load-bearing tissues. There is therefore a pressing need to develop microengineered tissue platforms that can recreate the highly inhomogeneous tissue microstructures that are known to influence mechanotransductive processes in normal and diseased tissue. Here, we report the quantification of proteoglycan-rich microdomains in developing, aging, and diseased fibrocartilaginous tissues, and the impact of these microdomains on endogenous cell responses to physiologic deformation within a native-tissue context. We also developed a method to generate heterogeneous tissue engineered constructs (hetTECs) with microscale non-fibrous proteoglycan-rich microdomains engineered into the fibrous structure, and show that these hetTECs match the microstructural, micromechanical, and mechanobiological benchmarks of native tissue. Our tissue engineered platform should facilitate the study of the mechanobiology of developing, homeostatic, degenerating, and regenerating fibrous tissues. PMID:26726994

  17. Iconic Native Culture Cues Inhibit Second Language Production in a Non-immigrant Population: Evidence from Bengali-English Bilinguals.

    PubMed

    Roychoudhuri, Kesaban S; Prasad, Seema G; Mishra, Ramesh K

    2016-01-01

    We examined if iconic pictures belonging to one's native culture interfere with second language production in bilinguals in an object naming task. Bengali-English bilinguals named pictures in both L1 and L2 against iconic cultural images representing Bengali culture or neutral images. Participants named in both "Blocked" and "Mixed" language conditions. In both conditions, participants were significantly slower in naming in English when the background was an iconic Bengali culture picture than a neutral image. These data suggest that native language culture cues lead to activation of the L1 lexicon that competed against L2 words creating an interference. These results provide further support to earlier observations where such culture related interference has been observed in bilingual language production. We discuss the results in the context of cultural influence on the psycholinguistic processes in bilingual object naming.

  18. New Evidence on the Price Effects of Cigarette Tax Competition

    PubMed Central

    Carpenter, Christopher S.; Mathes, Michael T.

    2016-01-01

    Multiple studies have shown that cigarette taxes are more than fully passed through to cigarette prices and that access to a nearby state with a lower cigarette tax also reduces local cigarette prices. We study two other sources of tax competition: nearby Native American reservations and online sales. Using quarterly data on local cigarette prices from 1976–2003, we show that the opening of a Native American casino within 25 miles of a city center is associated with a $0.016-$0.027 lower per-pack price, while a 50 percentage point increase in internet penetration is associated with a $0.22-$0.25 per-pack price reduction. These effects are not observed for other local prices for which there is no potential tax savings. Our results further our understanding of how tax competition affects local cigarette prices and provide context to studies linking Native American reservations and internet penetration to cigarette smuggling. PMID:27840571

  19. Versatile control of Plasmodium falciparum gene expression with an inducible protein-RNA interaction

    PubMed Central

    Goldfless, Stephen J.; Wagner, Jeffrey C.; Niles, Jacquin C.

    2014-01-01

    The available tools for conditional gene expression in Plasmodium falciparum are limited. Here, to enable reliable control of target gene expression, we build a system to efficiently modulate translation. We overcame several problems associated with other approaches for regulating gene expression in P. falciparum. Specifically, our system functions predictably across several native and engineered promoter contexts, and affords control over reporter and native parasite proteins irrespective of their subcellular compartmentalization. Induction and repression of gene expression are rapid, homogeneous, and stable over prolonged periods. To demonstrate practical application of our system, we used it to reveal direct links between antimalarial drugs and their native parasite molecular target. This is an important out come given the rapid spread of resistance, and intensified efforts to efficiently discover and optimize new antimalarial drugs. Overall, the studies presented highlight the utility of our system for broadly controlling gene expression and performing functional genetics in P. falciparum. PMID:25370483

  20. Proteomic data from human cell cultures refine mechanisms of chaperone-mediated protein homeostasis.

    PubMed

    Finka, Andrija; Goloubinoff, Pierre

    2013-09-01

    In the crowded environment of human cells, folding of nascent polypeptides and refolding of stress-unfolded proteins is error prone. Accumulation of cytotoxic misfolded and aggregated species may cause cell death, tissue loss, degenerative conformational diseases, and aging. Nevertheless, young cells effectively express a network of molecular chaperones and folding enzymes, termed here "the chaperome," which can prevent formation of potentially harmful misfolded protein conformers and use the energy of adenosine triphosphate (ATP) to rehabilitate already formed toxic aggregates into native functional proteins. In an attempt to extend knowledge of chaperome mechanisms in cellular proteostasis, we performed a meta-analysis of human chaperome using high-throughput proteomic data from 11 immortalized human cell lines. Chaperome polypeptides were about 10% of total protein mass of human cells, half of which were Hsp90s and Hsp70s. Knowledge of cellular concentrations and ratios among chaperome polypeptides provided a novel basis to understand mechanisms by which the Hsp60, Hsp70, Hsp90, and small heat shock proteins (HSPs), in collaboration with cochaperones and folding enzymes, assist de novo protein folding, import polypeptides into organelles, unfold stress-destabilized toxic conformers, and control the conformal activity of native proteins in the crowded environment of the cell. Proteomic data also provided means to distinguish between stable components of chaperone core machineries and dynamic regulatory cochaperones.

  1. The Evolving Contribution of Mass Spectrometry to Integrative Structural Biology

    NASA Astrophysics Data System (ADS)

    Faini, Marco; Stengel, Florian; Aebersold, Ruedi

    2016-06-01

    Protein complexes are key catalysts and regulators for the majority of cellular processes. Unveiling their assembly and structure is essential to understanding their function and mechanism of action. Although conventional structural techniques such as X-ray crystallography and NMR have solved the structure of important protein complexes, they cannot consistently deal with dynamic and heterogeneous assemblies, limiting their applications to small scale experiments. A novel methodological paradigm, integrative structural biology, aims at overcoming such limitations by combining complementary data sources into a comprehensive structural model. Recent applications have shown that a range of mass spectrometry (MS) techniques are able to generate interaction and spatial restraints (cross-linking MS) information on native complexes or to study the stoichiometry and connectivity of entire assemblies (native MS) rapidly, reliably, and from small amounts of substrate. Although these techniques by themselves do not solve structures, they do provide invaluable structural information and are thus ideally suited to contribute to integrative modeling efforts. The group of Brian Chait has made seminal contributions in the use of mass spectrometric techniques to study protein complexes. In this perspective, we honor the contributions of the Chait group and discuss concepts and milestones of integrative structural biology. We also review recent examples of integration of structural MS techniques with an emphasis on cross-linking MS. We then speculate on future MS applications that would unravel the dynamic nature of protein complexes upon diverse cellular states.

  2. Engineering tissue constructs to mimic native aortic and pulmonary valve leaflets' structures and mechanics

    NASA Astrophysics Data System (ADS)

    Masoumi, Nafiseh

    There are several disadvantages correlated with current heart valve replacement, including anticoagulation therapy for patients with mechanical valves and the low durability of bioprosthetic valves. The non-viable nature of such devices is a critical drawback especially for pediatric cases due to the inability of the graft to grow in vivo with the patients. A tissue engineered heart valve (TEHV) with remodeling and growth ability, is conceptually appealing to use in the surgical repair and could serve as a permanent replacements when operating for pediatric valvular lesions. It is critical that scaffolds for functional heart valve tissue engineering, be capable of mimicking the native leaflet's structure and mechanical properties at the time of implantation. Meanwhile, the scaffolds should be able to support cellular proliferation and native-like tissue formation as the TEHV remodels toward a scaffold-free state. Our overall hypothesis is that an "ideal" engineered construct, designed based on native leaflet's structure and mechanics, will complement a native heart valve leaflet in providing benchmarks for use in the design of clinically-applicable TEHV. This hypothesis was addressed through several experiments conducted in the present study. To establish a functional biomimetic TEHV, we developed scaffolds capable of matching the anisotropic stiffness of native leaflet while promoting native-like cell and collagen content and supporting the ECM generation. Scaffolds with various polymer contents (e.g., poly (glycerol sebacate) (PGS) and poly (epsilon-caprolactone) (PCL)) and structural designs (e.g., microfabricated and microfibrous scaffolds), were fabricated based on native leaflet's structure and mechanics. It was found that the tri-layered scaffold, designed with assembly of microfabricated PGS and microfibrous PGS/PCL was a functional leaflet capable of promoting tissue formation. Furthermore, to investigate the effect of cyclic stress and flexure individually on the TEHV development, we designed a simple and novel stretch-flexure bioreactor in which samples were subjected to well-defined stimulations with a controlled strain-rate. The stretch and flexure was found to accelerate and increase tissue formation on the microfabricated PGS scaffolds cultivated in the bioreactors.

  3. Interwoven Aligned Conductive Nanofiber Yarn/Hydrogel Composite Scaffolds for Engineered 3D Cardiac Anisotropy.

    PubMed

    Wu, Yaobin; Wang, Ling; Guo, Baolin; Ma, Peter X

    2017-06-27

    Mimicking the anisotropic cardiac structure and guiding 3D cellular orientation play a critical role in designing scaffolds for cardiac tissue regeneration. Significant advances have been achieved to control cellular alignment and elongation, but it remains an ongoing challenge for engineering 3D cardiac anisotropy using these approaches. Here, we present a 3D hybrid scaffold based on aligned conductive nanofiber yarns network (NFYs-NET, composition: polycaprolactone, silk fibroin, and carbon nanotubes) within a hydrogel shell for mimicking the native cardiac tissue structure, and further demonstrate their great potential for engineering 3D cardiac anisotropy for cardiac tissue engineering. The NFYs-NET structures are shown to control cellular orientation and enhance cardiomyocytes (CMs) maturation. 3D hybrid scaffolds were then fabricated by encapsulating NFYs-NET layers within hydrogel shell, and these 3D scaffolds performed the ability to promote aligned and elongated CMs maturation on each layer and individually control cellular orientation on different layers in a 3D environment. Furthermore, endothelialized myocardium was constructed by using this hybrid strategy via the coculture of CMs on NFYs-NET layer and endothelial cells within hydrogel shell. Therefore, these 3D hybrid scaffolds, containing NFYs-NET layer inducing cellular orientation, maturation, and anisotropy and hydrogel shell providing a suitable 3D environment for endothelialization, has great potential in engineering 3D cardiac anisotropy.

  4. International Students' Attitudes Towards Malaysian English Ethnolects

    ERIC Educational Resources Information Center

    Khojastehrad, Shadi; Rafik-Galea, Shameem; Abdullah, Ain Nadzimah

    2015-01-01

    Language attitudes are learned and formed in our social environment through hearing others referring to certain groups or people's languages and cultures, and also by exposure to particular varieties spoken in the context. This might lead to stereotyping English and its native speakers (McKenzie, 2008). In this sense, it is pedagogically…

  5. Successful L3 Learning in a Study Abroad Context: A Personal Narrative

    ERIC Educational Resources Information Center

    Róg, Tomasz

    2017-01-01

    Studying abroad may seem like an unparalleled opportunity to learn a foreign language. Massive exposure to the language, chances for interaction with native speakers, and cultural immersion appear to create excellent conditions for language learning. Yet, most available research indicates that study abroad (SA) participants rarely achieve…

  6. Child Socialization among Native Americans: The Lakota (Sioux) in Cultural Context.

    ERIC Educational Resources Information Center

    Medicine, Beatrice

    1985-01-01

    Child socialization research among American Indians must account for tribal differences, examining gender roles in a given tribal culture, and employing studies of enculturation and acculturation, life histories, and ethnographies. Child socialization in the Teton Sioux or Lakota tribe can be used to illustrate these research techniques. The…

  7. Personalised Context-Aware Ubiquitous Learning System for Supporting Effective English Vocabulary Learning

    ERIC Educational Resources Information Center

    Chen, Chih-Ming; Li, Yi-Lun

    2010-01-01

    Because learning English is extremely popular in non-native English speaking countries, developing modern assisted-learning schemes that facilitate effective English learning is a critical issue in English-language education. Vocabulary learning is vital within English learning because vocabulary comprises the basic building blocks of English…

  8. Exploring Intercultural Interactions in Multicultural Contexts: Proposal and Research Suggestions.

    ERIC Educational Resources Information Center

    Yeh, Jung-huel Becky

    A discussion examines the importance of communication between non-native speakers (NNS/NNS), reviews relevant theories and issues in intercultural interactions and NNS/NNS interactions, and explores methodological issues in interpreting linguistic and interactional data. The intent is to explore features of communication between NNSs from…

  9. "Two Spirits, Nadleeh," and LGBTQ2 Navajo Gaze

    ERIC Educational Resources Information Center

    Estrada, Gabriel S.

    2011-01-01

    In reading queer Native American images, Lisa Tatonetti (2010) criticizes film in which the "boundaries of nation in indigenous contexts are constructed and maintained by the heteronormative gaze" that restricts lesbian, gay, bisexual, transgender, queer, and two-spirit (LGBTQ2) representations. The author's own work differentiates the mere…

  10. Indian Education in America: 8 Essays.

    ERIC Educational Resources Information Center

    Deloria, Vine, Jr.

    This book presents eight essays by Vine Deloria, Jr., a Standing Rock Sioux and professor of political science at the University of Colorado. Essays examine issues facing Native American students as they progress through the educational system, and aim to help Indian students place Western knowledge into the context of tribal and community…

  11. Social Factors, Interlanguage and Language Learning.

    ERIC Educational Resources Information Center

    Richards, Jack C.

    This paper considers a number of diverse contexts in which English is learned as a second language and in which nonstandard dialects arise because of social and linguistic factors. The varieties considered here are immigrant English, indigenous-minority varieties of English, pidginization and creolization, local varieties of non-native English,…

  12. Somalia: Country Status Report.

    ERIC Educational Resources Information Center

    McFerren, Margaret

    A survey of the status of language usage in Somalia begins with an overview of the usage patterns of Somali, the official language, and three languages previously used officially: English, Italian, and Arabic. The cultural context that for many years has supported the usage of a single native language for communication and administration is also…

  13. Immigrant Students' Achievements in Croatia, Serbia and Slovenia in Context

    ERIC Educational Resources Information Center

    Šori, Iztok; Šušteric, Nika; Gaber, Slavko

    2011-01-01

    Achievement gaps between immigrant and native students indicate failure to assure educational equity in the majority of countries assessed by the Programme for International Student Assessment in 2009 (PISA, 2009). The present article explains disparate achievement results in Europe, first testing the hypothesis of old and new democracies. In…

  14. Receptive Multilingualism in the Swiss Army

    ERIC Educational Resources Information Center

    Berthele, Raphael; Wittlin, Gabriele

    2013-01-01

    In this paper a particular context where receptive multilingualism at work can be observed is discussed. The Swiss armed forces underwent a series of quite dramatic downsizing measures, which lead to a situation with increased amount of mixed groups and linguistically mixed situations regarding the first/native language of officers and the…

  15. The Native American Experience. American Historical Images on File.

    ERIC Educational Resources Information Center

    Wardwell, Lelia, Ed.

    This photo-documentation reference body presents more than 275 images chronicling the experiences of the American Indian from their prehistoric migrations to the present. The volume includes information and images illustrating the life ways of various tribes. The images are accompanied by historical information providing cultural context. The book…

  16. Hierarchical Linear Modelling of Student and School Effects on Academic Achievement.

    ERIC Educational Resources Information Center

    Ma, Xin; Klinger, Don A.

    2000-01-01

    Used hierarchical linear modeling with data from the New Brunswick School Climate Study (Canada) to examine student background, school context, and school climate effects on Grade 6 student achievement in mathematics, science, reading, and writing. Gender, socioeconomic status, and Native ethnicity were significant predictors of academic…

  17. A COMPUTERIZED SURVEY QUESTIONNAIRE TO ASSIST TRIBAL REPRESENTATIVES IN GATHERING DATA ON TRIBAL FISH CONSUMPTION FOR RISK ASSESSMENT

    EPA Science Inventory

    Context
    EPA Region 10, which comprises Alaska, Washington, Idaho, and Oregon, has 269 federally recognized Native American Tribes. It is has been documented that Tribal members consume much larger quantities of fish than the general population. ORD's Human Studies Division...

  18. Perceived Foreign Accent: Extended Stays Abroad, Level of Instruction, and Motivation

    ERIC Educational Resources Information Center

    Martinsen, Rob A.; Alvord, Scott M.; Tanner, Joshua

    2014-01-01

    Studies have examined various factors that affect pronunciation including phonetic context, style variation, first language transfer, and experience abroad. A plethora of research has also linked motivation to higher levels of proficiency in the second language. The present study uses native speaker ratings and multiple regression analysis to…

  19. Teacher Deployment of "Oh" in Known-Answer Question Sequences

    ERIC Educational Resources Information Center

    Hosoda, Yuri

    2016-01-01

    This conversation analytic study describes some specific interactional contexts in which native English-speaking teachers produce "oh" in known-answer question sequences in English language classes. The data for this study come from 10 video-recorded Japanese primary school English language class sessions. The analysis identified three…

  20. Cellular and synaptic network defects in autism

    PubMed Central

    Peça, João; Feng, Guoping

    2012-01-01

    Many candidate genes are now thought to confer susceptibility to autism spectrum disorder (ASD). Here we review four interrelated complexes, each composed of multiple families of genes that functionally coalesce on common cellular pathways. We illustrate a common thread in the organization of glutamatergic synapses and suggest a link between genes involved in Tuberous Sclerosis Complex, Fragile X syndrome, Angelman syndrome and several synaptic ASD candidate genes. When viewed in this context, progress in deciphering the molecular architecture of cellular protein-protein interactions together with the unraveling of synaptic dysfunction in neural networks may prove pivotal to advancing our understanding of ASDs. PMID:22440525

  1. Cell-Based Therapeutics: The Next Pillar of Medicine

    PubMed Central

    Fischbach, Michael A.; Bluestone, Jeffrey A.; Lim, Wendell A.

    2013-01-01

    Two decades ago, the pharmaceutical industry—long dominated by small-molecule drugs—was revolutionized by the the advent of biologics. Today, biomedicine sits on the cusp of a new revolution: the use of microbial and human cells as versatile therapeutic engines. Here, we discuss the promise of this “third pillar” of therapeutics in the context of current scientific, regulatory, economic, and perceptual challenges. History suggests that the advent of cellular medicines will require the development of a foundational cellular engineering science that provides a systematic framework for safely and predictably altering and regulating cellular behaviors. PMID:23552369

  2. Listening to the Voices of Native Hawaiian Elders and ‘Ohana Caregivers: Discussions on Aging, Health, and Care Preferences

    PubMed Central

    Mokuau, Noreen; Ka’opua, Lana S.; Kim, Bum Jung; Higuchi, Paula; Braun, Kathryn L.

    2015-01-01

    Native Hawaiians, the indigenous people of Hawai’i, are affected by varying social and health disparities that result in high prevalence of chronic disease, early onset of disability, and shorter life expectancy compared to other ethnic groups in Hawai’i. Six listening meetings were conducted, involving 41 community-dwelling kūpuna (Native Hawaiian elders) and ‘ohana (family) caregivers to investigate health and care preferences that offer the potential for improving well-being in later life for Native Hawaiian elders. As background, we provide three explanatory perspectives and theories—life course perspective, minority stress theory, and historical trauma—that guided the design of this study and provided the study’s context. A number of overarching themes and subthemes were identified, some of which point to universal concerns with age and caregiving (such as challenges and costs associated with growing old and caregiving) and others that are culturally specific (such as influence of culture and social stressors, including discrimination, on health needs and care preferences). Results give further support to the urgency of affordable, accessible, and acceptable programs and policies that can respond to the growing health and care needs of native elders and family caregivers. PMID:24659060

  3. Tualang Honey Improves Human Corneal Epithelial Progenitor Cell Migration and Cellular Resistance to Oxidative Stress In Vitro

    PubMed Central

    Tan, Jun Jie; Azmi, Siti Maisura; Yong, Yoke Keong; Cheah, Hong Leong; Lim, Vuanghao; Sandai, Doblin; Shaharuddin, Bakiah

    2014-01-01

    Stem cells with enhanced resistance to oxidative stress after in vitro expansion have been shown to have improved engraftment and regenerative capacities. Such cells can be generated by preconditioning them with exposure to an antioxidant. In this study we evaluated the effects of Tualang honey (TH), an antioxidant-containing honey, on human corneal epithelial progenitor (HCEP) cells in culture. Cytotoxicity, gene expression, migration, and cellular resistance to oxidative stress were evaluated. Immunofluorescence staining revealed that HCEP cells were holoclonal and expressed epithelial stem cell marker p63 without corneal cytokeratin 3. Cell viability remained unchanged after cells were cultured with 0.004, 0.04, and 0.4% TH in the medium, but it was significantly reduced when the concentration was increased to 3.33%. Cell migration, tested using scratch migration assay, was significantly enhanced when cells were cultured with TH at 0.04% and 0.4%. We also found that TH has hydrogen peroxide (H2O2) scavenging ability, although a trace level of H2O2 was detected in the honey in its native form. Preconditioning HCEP cells with 0.4% TH for 48 h showed better survival following H2O2-induced oxidative stress at 50 µM than untreated group, with a significantly lower number of dead cells (15.3±0.4%) were observed compared to the untreated population (20.5±0.9%, p<0.01). Both TH and ascorbic acid improved HCEP viability following induction of 100 µM H2O2, but the benefit was greater with TH treatment than with ascorbic acid. However, no significant advantage was demonstrated using 5-hydroxymethyl-2-furancarboxaldehyde, a compound that was found abundant in TH using GC/MS analysis. This suggests that the cellular anti-oxidative capacity in HCEP cells was augmented by native TH and was attributed to its antioxidant properties. In conclusion, TH possesses antioxidant properties and can improve cell migration and cellular resistance to oxidative stress in HCEP cells in vitro. PMID:24802273

  4. Gut microbiomes of mobile predators vary with landscape context and species identity.

    PubMed

    Tiede, Julia; Scherber, Christoph; Mutschler, James; McMahon, Katherine D; Gratton, Claudio

    2017-10-01

    Landscape context affects predator-prey interactions and predator diet composition, yet little is known about landscape effects on insect gut microbiomes, a determinant of physiology and condition. Here, we combine laboratory and field experiments to examine the effects of landscape context on the gut bacterial community and body condition of predatory insects. Under laboratory conditions, we found that prey diversity increased bacterial richness in insect guts. In the field, we studied the performance and gut microbiota of six predatory insect species along a landscape complexity gradient in two local habitat types (soybean fields vs. prairie). Insects from soy fields had richer gut bacteria and lower fat content than those from prairies, suggesting better feeding conditions in prairies. Species origin mediated landscape context effects, suggesting differences in foraging of exotic and native predators on a landscape scale. Overall, our study highlights complex interactions among gut microbiota, predator identity, and landscape context.

  5. Treatment Analysis in a Cancer Stem Cell Context Using a Tumor Growth Model Based on Cellular Automata.

    PubMed

    Monteagudo, Ángel; Santos, José

    2015-01-01

    Cancer can be viewed as an emergent behavior in terms of complex system theory and artificial life, Cellular Automata (CA) being the tool most used for studying and characterizing the emergent behavior. Different approaches with CA models were used to model cancer growth. The use of the abstract model of acquired cancer hallmarks permits the direct modeling at cellular level, where a cellular automaton defines the mitotic and apoptotic behavior of cells, and allows for an analysis of different dynamics of the cellular system depending on the presence of the different hallmarks. A CA model based on the presence of hallmarks in the cells, which includes a simulation of the behavior of Cancer Stem Cells (CSC) and their implications for the resultant growth behavior of the multicellular system, was employed. This modeling of cancer growth, in the avascular phase, was employed to analyze the effect of cancer treatments in a cancer stem cell context. The model clearly explains why, after treatment against non-stem cancer cells, the regrowth capability of CSCs generates a faster regrowth of tumor behavior, and also shows that a continuous low-intensity treatment does not favor CSC proliferation and differentiation, thereby allowing an unproblematic control of future tumor regrowth. The analysis performed indicates that, contrary to the current attempts at CSC control, trying to make CSC proliferation more difficult is an important point to consider, especially in the immediate period after a standard treatment for controlling non-stem cancer cell proliferation.

  6. In silico methods for co-transcriptional RNA secondary structure prediction and for investigating alternative RNA structure expression.

    PubMed

    Meyer, Irmtraud M

    2017-05-01

    RNA transcripts are the primary products of active genes in any living organism, including many viruses. Their cellular destiny not only depends on primary sequence signals, but can also be determined by RNA structure. Recent experimental evidence shows that many transcripts can be assigned more than a single functional RNA structure throughout their cellular life and that structure formation happens co-transcriptionally, i.e. as the transcript is synthesised in the cell. Moreover, functional RNA structures are not limited to non-coding transcripts, but can also feature in coding transcripts. The picture that now emerges is that RNA structures constitute an additional layer of information that can be encoded in any RNA transcript (and on top of other layers of information such as protein-context) in order to exert a wide range of functional roles. Moreover, different encoded RNA structures can be expressed at different stages of a transcript's life in order to alter the transcript's behaviour depending on its actual cellular context. Similar to the concept of alternative splicing for protein-coding genes, where a single transcript can yield different proteins depending on cellular context, it is thus appropriate to propose the notion of alternative RNA structure expression for any given transcript. This review introduces several computational strategies that my group developed to detect different aspects of RNA structure expression in vivo. Two aspects are of particular interest to us: (1) RNA secondary structure features that emerge during co-transcriptional folding and (2) functional RNA structure features that are expressed at different times of a transcript's life and potentially mutually exclusive. Copyright © 2017. Published by Elsevier Inc.

  7. Pollen tube energetics: respiration, fermentation and the race to the ovule

    PubMed Central

    Rounds, Caleb M.; Winship, Lawrence J.; Hepler, Peter K.

    2011-01-01

    Background Pollen tubes grow by transferring chemical energy from stored cellular starch and newly assimilated sugars into ATP. This drives myriad processes essential for cell elongation, directly or through the creation of ion gradients. Respiration plays a central role in generating and regulating this energy flow and thus in the success of plant reproduction. Pollen tubes are easily grown in vitro and have become an excellent model for investigating the contributions of respiration to plant cellular growth and morphogenesis at the molecular, biochemical and physiological levels. Scope In recent decades, pollen tube research has become increasingly focused on the molecular mechanisms involved in cellular processes. Yet, effective growth and development requires an intact, integrated set of cellular processes, all supplied with a constant flow of energy. Here we bring together information from the current and historical literature concerning respiration, fermentation and mitochondrial physiology in pollen tubes, and assess the significance of more recent molecular and genetic investigations in a physiological context. Conclusions The rapid growth of the pollen tube down the style has led to the evolution of high rates of pollen tube respiration. Respiration rates in lily predict a total energy turnover of 40–50 fmol ATP s−1 per pollen grain. Within this context we examine the energetic requirements of cell wall synthesis, osmoregulation, actin dynamics and cyclosis. At present, we can only estimate the amount of energy required, because data from growing pollen tubes are not available. In addition to respiration, we discuss fermentation and mitochondrial localization. We argue that the molecular pathways need to be examined within the physiological context to understand better the mechanisms that control tip growth in pollen tubes. PMID:22476489

  8. Development of viral nanoparticles for efficient intracellular delivery

    NASA Astrophysics Data System (ADS)

    Wu, Zhuojun; Chen, Kevin; Yildiz, Ibrahim; Dirksen, Anouk; Fischer, Rainer; Dawson, Philip E.; Steinmetz, Nicole F.

    2012-05-01

    Viral nanoparticles (VNPs) based on plant viruses such as Cowpea mosaic virus (CPMV) can be used for a broad range of biomedical applications because they present a robust scaffold that allows functionalization by chemical conjugation and genetic modification, thereby offering an efficient drug delivery platform that can target specific cells and tissues. VNPs such as CPMV show natural affinity to cells; however, cellular uptake is inefficient. Here we show that chemical modification of the CPMV surface with a highly reactive, specific and UV-traceable hydrazone linker allows bioconjugation of polyarginine (R5) cell penetrating peptides (CPPs), which can overcome these limitations. The resulting CPMV-R5 particles were taken up into a human cervical cancer cell line (HeLa) more efficiently than native particles. Uptake efficiency was dependent on the density of R5 peptides on the surface of the VNP; particles displaying 40 R5 peptides per CPMV (denoted as CPMV-R5H) interact strongly with the plasma membrane and are taken up into the cells via an energy-dependent mechanism whereas particles displaying 10 R5 peptides per CPMV (CPMV-R5L) are only slowly taken up. The fate of CPMV-R5 versus native CPMV particles within cells was evaluated in a co-localization time course study. It was indicated that the intracellular localization of CPMV-R5 and CPMV differs; CPMV remains trapped in Lamp-1 positive endolysosomes over long time frames; in contrast, 30-50% of the CPMV-R5 particles transitioned from the endosome into other cellular vesicles or compartments. Our data provide the groundwork for the development of efficient drug delivery formulations based on CPMV-R5.Viral nanoparticles (VNPs) based on plant viruses such as Cowpea mosaic virus (CPMV) can be used for a broad range of biomedical applications because they present a robust scaffold that allows functionalization by chemical conjugation and genetic modification, thereby offering an efficient drug delivery platform that can target specific cells and tissues. VNPs such as CPMV show natural affinity to cells; however, cellular uptake is inefficient. Here we show that chemical modification of the CPMV surface with a highly reactive, specific and UV-traceable hydrazone linker allows bioconjugation of polyarginine (R5) cell penetrating peptides (CPPs), which can overcome these limitations. The resulting CPMV-R5 particles were taken up into a human cervical cancer cell line (HeLa) more efficiently than native particles. Uptake efficiency was dependent on the density of R5 peptides on the surface of the VNP; particles displaying 40 R5 peptides per CPMV (denoted as CPMV-R5H) interact strongly with the plasma membrane and are taken up into the cells via an energy-dependent mechanism whereas particles displaying 10 R5 peptides per CPMV (CPMV-R5L) are only slowly taken up. The fate of CPMV-R5 versus native CPMV particles within cells was evaluated in a co-localization time course study. It was indicated that the intracellular localization of CPMV-R5 and CPMV differs; CPMV remains trapped in Lamp-1 positive endolysosomes over long time frames; in contrast, 30-50% of the CPMV-R5 particles transitioned from the endosome into other cellular vesicles or compartments. Our data provide the groundwork for the development of efficient drug delivery formulations based on CPMV-R5. Electronic supplementary information (ESI) available: Experimental details and additional supporting data. See DOI: 10.1039/c2nr30366c

  9. Recontextualising Cellular Respiration in Upper Secondary Biology Education. Characteristics and Practicability of a Learning and Teaching Strategy

    ERIC Educational Resources Information Center

    Wierdsma, Menno; Knippels, Marie-Christine; van Oers, Bert; Boersma, Kerst

    2016-01-01

    Since concepts may have different meanings in different contexts, students have to learn to recontextualise them, i.e. to adapt their meanings to a new context. It is unclear, however, what characteristics a learning and teaching strategy for recontextualising should have. The study aims to develop such a learning and teaching strategy for…

  10. Tracking of Short Distance Transport Pathways in Biological Tissues by Ultra-Small Nanoparticles

    NASA Astrophysics Data System (ADS)

    Segmehl, Jana S.; Lauria, Alessandro; Keplinger, Tobias; Berg, John K.; Burgert, Ingo

    2018-03-01

    In this work, ultra-small europium-doped HfO2 nanoparticles were infiltrated into native wood and used as trackers for studying penetrability and diffusion pathways in the hierarchical wood structure. The high electron density, laser induced luminescence, and crystallinity of these particles allowed for a complementary detection of the particles in the cellular tissue. Confocal Raman microscopy and high-resolution synchrotron scanning wide-angle X-ray scattering (WAXS) measurements were used to detect the infiltrated particles in the native wood cell walls. This approach allows for simultaneously obtaining chemical information of the probed biological tissue and the spatial distribution of the integrated particles. The in-depth information about particle distribution in the complex wood structure can be used for revealing transport pathways in plant tissues, but also for gaining better understanding of modification treatments of plant scaffolds aiming at novel functionalized materials.

  11. Injectable Hydrogel Scaffold from Decellularized Human Lipoaspirate

    PubMed Central

    Young, D. Adam; Ibrahim, Dina O.; Hu, Diane; Christman, Karen L.

    2010-01-01

    Soft tissue fillers are rapidly gaining popularity for aesthetic improvements or repair of adipose tissue deficits. Several injectable biopolymers have been investigated for this purpose but often face rapid resorption or limited adipogenesis, and do not mimic the native adipose extracellular matrix (ECM). We have generated an injectable adipose matrix scaffold by efficiently removing both the cellular and lipid contents of human lipoaspirate. The decellularized material retained a complex composition of peptides and glycosaminoglycans found in native adipose ECM. This matrix can be further processed by solubilizing the extracted ECM to generate a thermally-responsive hydrogel that self-assembles upon subcutaneous injection. This hydrogel also supports the growth and survival of patient matched adipose - derived stem cells in vitro. The development of an injectable hydrogel from human lipoaspirate represents a minimally-invasive option for adipose tissue engineering in terms of both the collection of source material and delivery of the scaffold. PMID:20932943

  12. Repositioning tolcapone as a potent inhibitor of transthyretin amyloidogenesis and associated cellular toxicity

    PubMed Central

    Sant'Anna, Ricardo; Gallego, Pablo; Robinson, Lei Z.; Pereira-Henriques, Alda; Ferreira, Nelson; Pinheiro, Francisca; Esperante, Sebastian; Pallares, Irantzu; Huertas, Oscar; Rosário Almeida, Maria; Reixach, Natàlia; Insa, Raul; Velazquez-Campoy, Adrian; Reverter, David; Reig, Núria; Ventura, Salvador

    2016-01-01

    Transthyretin (TTR) is a plasma homotetrameric protein implicated in fatal systemic amyloidoses. TTR tetramer dissociation precedes pathological TTR aggregation. Native state stabilizers are promising drugs to treat TTR amyloidoses. Here we repurpose tolcapone, an FDA-approved molecule for Parkinson's disease, as a potent TTR aggregation inhibitor. Tolcapone binds specifically to TTR in human plasma, stabilizes the native tetramer in vivo in mice and humans and inhibits TTR cytotoxicity. Crystal structures of tolcapone bound to wild-type TTR and to the V122I cardiomyopathy-associated variant show that it docks better into the TTR T4 pocket than tafamidis, so far the only drug on the market to treat TTR amyloidoses. These data indicate that tolcapone, already in clinical trials for familial amyloid polyneuropathy, is a strong candidate for therapeutic intervention in these diseases, including those affecting the central nervous system, for which no small-molecule therapy exists. PMID:26902880

  13. Extracellular Matrix Scaffold Technology for Bioartificial Pancreas Engineering

    PubMed Central

    Salvatori, Marcus; Katari, Ravi; Patel, Timil; Peloso, Andrea; Mugweru, Jon; Owusu, Kofi

    2014-01-01

    Emergent technologies in regenerative medicine may soon overcome the limitations of conventional diabetes therapies. Collaborative efforts across the subfields of stem cell technology, islet encapsulation, and biomaterial carriers seek to produce a bioengineered pancreas capable of restoring endocrine function in patients with insulin-dependent diabetes. These technologies rely on a robust understanding of the extracellular matrix (ECM), the supportive 3-dimensional network of proteins necessary for cellular attachment, proliferation, and differentiation. Although these functions can be partially approximated by biosynthetic carriers, novel decellularization protocols have allowed researchers to discover the advantages afforded by the native pancreatic ECM. The native ECM has proven to be an optimal platform for recellularization and whole-organ pancreas bioengineering, an exciting new field with the potential to resolve the dire shortage of transplantable organs. This review seeks to contextualize recent findings, discuss current research goals, and identify future challenges of regenerative medicine as it applies to diabetes management. PMID:24876552

  14. A molecular mechanism of chaperone-client recognition

    PubMed Central

    He, Lichun; Sharpe, Timothy; Mazur, Adam; Hiller, Sebastian

    2016-01-01

    Molecular chaperones are essential in aiding client proteins to fold into their native structure and in maintaining cellular protein homeostasis. However, mechanistic aspects of chaperone function are still not well understood at the atomic level. We use nuclear magnetic resonance spectroscopy to elucidate the mechanism underlying client recognition by the adenosine triphosphate-independent chaperone Spy at the atomic level and derive a structural model for the chaperone-client complex. Spy interacts with its partially folded client Im7 by selective recognition of flexible, locally frustrated regions in a dynamic fashion. The interaction with Spy destabilizes a partially folded client but spatially compacts an unfolded client conformational ensemble. By increasing client backbone dynamics, the chaperone facilitates the search for the native structure. A comparison of the interaction of Im7 with two other chaperones suggests that the underlying principle of recognizing frustrated segments is of a fundamental nature. PMID:28138538

  15. How to Make a Heart Valve: From Embryonic Development to Bioengineering of Living Valve Substitutes

    PubMed Central

    MacGrogan, Donal; Luxán, Guillermo; Driessen-Mol, Anita; Bouten, Carlijn; Baaijens, Frank; de la Pompa, José Luis

    2014-01-01

    Cardiac valve disease is a significant cause of ill health and death worldwide, and valve replacement remains one of the most common cardiac interventions in high-income economies. Despite major advances in surgical treatment, long-term therapy remains inadequate because none of the current valve substitutes have the potential for remodeling, regeneration, and growth of native structures. Valve development is coordinated by a complex interplay of signaling pathways and environmental cues that cause disease when perturbed. Cardiac valves develop from endocardial cushions that become populated by valve precursor mesenchyme formed by an epithelial–mesenchymal transition (EMT). The mesenchymal precursors, subsequently, undergo directed growth, characterized by cellular compartmentalization and layering of a structured extracellular matrix (ECM). Knowledge gained from research into the development of cardiac valves is driving exploration into valve biomechanics and tissue engineering directed at creating novel valve substitutes endowed with native form and function. PMID:25368013

  16. Perturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies

    PubMed Central

    2018-01-01

    Membrane proteins perform a host of vital cellular functions. Deciphering the molecular mechanisms whereby they fulfill these functions requires detailed biophysical and structural investigations. Detergents have proven pivotal to extract the protein from its native surroundings. Yet, they provide a milieu that departs significantly from that of the biological membrane, to the extent that the structure, the dynamics, and the interactions of membrane proteins in detergents may considerably vary, as compared to the native environment. Understanding the impact of detergents on membrane proteins is, therefore, crucial to assess the biological relevance of results obtained in detergents. Here, we review the strengths and weaknesses of alkyl phosphocholines (or foscholines), the most widely used detergent in solution-NMR studies of membrane proteins. While this class of detergents is often successful for membrane protein solubilization, a growing list of examples points to destabilizing and denaturing properties, in particular for α-helical membrane proteins. Our comprehensive analysis stresses the importance of stringent controls when working with this class of detergents and when analyzing the structure and dynamics of membrane proteins in alkyl phosphocholine detergents. PMID:29488756

  17. Enhanced nutrient transport improves the depth-dependent properties of tri-layered engineered cartilage constructs with zonal co-culture of chondrocytes and MSCs.

    PubMed

    Kim, Minwook; Farrell, Megan J; Steinberg, David R; Burdick, Jason A; Mauck, Robert L

    2017-08-01

    Biomimetic design in cartilage tissue engineering is a challenge given the complexity of the native tissue. While numerous studies have generated constructs with near-native bulk properties, recapitulating the depth-dependent features of native tissue remains a challenge. Furthermore, limitations in nutrient transport and matrix accumulation in engineered constructs hinders maturation within the central core of large constructs. To overcome these limitations, we fabricated tri-layered constructs that recapitulate the depth-dependent cellular organization and functional properties of native tissue using zonally derived chondrocytes co-cultured with MSCs. We also introduced porous hollow fibers (HFs) and HFs/cotton threads to enhance nutrient transport. Our results showed that tri-layered constructs with depth-dependent organization and properties could be fabricated. The addition of HFs or HFs/threads improved matrix accumulation in the central core region. With HF/threads, the local modulus in the deep region of tri-layered constructs nearly matched that of native tissue, though the properties in the central regions remained lower. These constructs reproduced the zonal organization and depth-dependent properties of native tissue, and demonstrate that a layer-by-layer fabrication scheme holds promise for the biomimetic repair of focal cartilage defects. Articular cartilage is a highly organized tissue driven by zonal heterogeneity of cells, extracellular matrix proteins and fibril orientations, resulting in depth-dependent mechanical properties. Therefore, the recapitulation of the functional properties of native cartilage in a tissue engineered construct requires such a biomimetic design of the morphological organization, and this has remained a challenge in cartilage tissue engineering. This study demonstrates that a layer-by-layer fabrication scheme, including co-cultures of zone-specific articular CHs and MSCs, can reproduce the depth-dependent characteristics and mechanical properties of native cartilage while minimizing the need for large numbers of chondrocytes. In addition, introduction of a porous hollow fiber (combined with a cotton thread) enhanced nutrient transport and depth-dependent properties of the tri-layered construct. Such a tri-layered construct may provide critical advantages for focal cartilage repair. These constructs hold promise for restoring native tissue structure and function, and may be beneficial in terms of zone-to-zone integration with adjacent host tissue and providing more appropriate strain transfer after implantation. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  18. Potential future scenarios for Australia's native biodiversity given on-going increases in human population.

    PubMed

    Pepper, D A; Lada, Hania; Thomson, James R; Bakar, K Shuvo; Lake, P S; Mac Nally, Ralph

    2017-01-15

    Most natural assets, including native biodiversity (our focus), are under increasing threat from direct (loss of habitat, hunting) and indirect (climate change) human actions. Most human impacts arise from increasing human populations coupled with rises in per capita resource use. The rates of change of human actions generally outpace those to which the biota can respond or adapt. If we are to maintain native biodiversity, then we must develop ways to envisage how the biota may be affected over the next several decades to guide management and policy responses. We consider the future for Australia's native biodiversity in the context of two assumptions. First, the human population in Australia will be 40million by 2050, which has been mooted by federal government agencies. Second, greenhouse gas emissions will track the highest rates considered by the Intergovernmental Panel on Climate Change. The scenarios are based on major drivers of change, which were constructed from seven key drivers of change pertinent to native biodiversity. Five scenarios deal with differing distributions of the human population driven by uncertainties in climate change and in the human responses to climate change. Other scenarios are governed largely by global change and explore different rates of resource use, unprecedented rates of technological change, capabilities and societal values. A narrative for each scenario is provided. The set of scenarios spans a wide range of possible future paths for Australia, with different implications for the future of native biodiversity. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. “The Poison That Ruined the Nation”: Native American Men—Alcohol, Identity, and Traditional Healing

    PubMed Central

    Matamonasa-Bennett, Arieahn

    2015-01-01

    Alcoholism and destructive drinking patterns are serious social problems in many Native American reservation and urban communities. This qualitative study of men from a single Great Lakes reservation community examined the social, cultural, and psychological aspects of their alcohol problems through their life stories. The men were in various stages of recovery and sobriety, and data collection consisted of open-ended interviews and analysis utilizing principles and techniques from grounded theory and ethnographic content analysis. Alcoholism and other serious social problems facing Native American communities need to be understood in the sociocultural and historical contexts of colonization and historical grief and trauma. This study suggests that for Native American men, there are culturally specific perspectives on alcohol that have important implications for prevention and treatment of alcohol abuse. The participants’ narratives provided insight into the ways reconnecting with traditional cultural values (retraditionalization) helped them achieve sobriety. For these men, alcohol was highly symbolic of colonization as well as a protest to it. Alcohol was a means for affirming “Indian” identity and sobriety a means for reaffirming traditional tribal identity. Their narratives suggested the ways in which elements of traditional cultural values and practices facilitate healing in syncretic models and Nativized treatment. Understanding the ways in which specific Native cultural groups perceive their problems with drinking and sobriety can create more culturally congruent, culturally sensitive, and effective treatment approaches and inform future research. PMID:25812975

  20. Ionotropic AMPA-type glutamate and metabotropic GABAB receptors: determining cellular physiology by proteomes.

    PubMed

    Bettler, Bernhard; Fakler, Bernd

    2017-08-01

    Ionotropic AMPA-type glutamate receptors and G-protein-coupled metabotropic GABA B receptors are key elements of neurotransmission whose cellular functions are determined by their protein constituents. Over the past couple of years unbiased proteomic approaches identified comprehensive sets of protein building blocks of these two types of neurotransmitter receptors in the brain (termed receptor proteomes). This provided the opportunity to match receptor proteomes with receptor physiology and to study the structural organization, regulation and function of native receptor complexes in an unprecedented manner. In this review we discuss the principles of receptor architecture and regulation emerging from the functional characterization of the proteomes of AMPA and GABA B receptors. We also highlight progress in unraveling the role of unexpected protein components for receptor physiology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Engineering Cellular Metabolism.

    PubMed

    Nielsen, Jens; Keasling, Jay D

    2016-03-10

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds, and pharmaceuticals. However, making cells into efficient factories is challenging because cells have evolved robust metabolic networks with hard-wired, tightly regulated lines of communication between molecular pathways that resist efforts to divert resources. Here, we will review the current status and challenges of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Cellular and Pharmacological Targets to Induce Coronary Arteriogenesis

    PubMed Central

    Hollander, Maurits R.; Horrevoets, Anton J.G.; van Royen, Niels

    2014-01-01

    The formation of collateral vessels (arteriogenesis) to sustain perfusion in ischemic tissue is native to the body and can compensate for coronary stenosis. However, arteriogenesis is a complex process and is dependent on many different factors. Although animal studies on collateral formation and stimulation show promising data, clinical trials have failed to replicate these results. Further research to the exact mechanisms is needed in order to develop a pharmalogical stimulant. This review gives an overview of recent data in the field of arteriogenesis. PMID:23638831

  3. Expression of phosphoinositide-specific phospholipase C isoforms in native endothelial cells.

    PubMed

    Béziau, Delphine M; Toussaint, Fanny; Blanchette, Alexandre; Dayeh, Nour R; Charbel, Chimène; Tardif, Jean-Claude; Dupuis, Jocelyn; Ledoux, Jonathan

    2015-01-01

    Phospholipase C (PLC) comprises a superfamily of enzymes that play a key role in a wide array of intracellular signalling pathways, including protein kinase C and intracellular calcium. Thirteen different mammalian PLC isoforms have been identified and classified into 6 families (PLC-β, γ, δ, ε, ζ and η) based on their biochemical properties. Although the expression of PLC isoforms is tissue-specific, concomitant expression of different PLC has been reported, suggesting that PLC family is involved in multiple cellular functions. Despite their critical role, the PLC isoforms expressed in native endothelial cells (ECs) remains undetermined. A conventional PCR approach was initially used to elucidate the mRNA expression pattern of PLC isoforms in 3 distinct murine vascular beds: mesenteric (MA), pulmonary (PA) and middle cerebral arteries (MCA). mRNA encoding for most PLC isoforms was detected in MA, MCA and PA with the exception of η2 and β2 (only expressed in PA), δ4 (only expressed in MCA), η1 (expressed in all but MA) and ζ (not detected in any vascular beds tested). The endothelial-specific PLC expression was then sought in freshly isolated ECs. Interestingly, the PLC expression profile appears to differ across the investigated arterial beds. While mRNA for 8 of the 13 PLC isoforms was detected in ECs from MA, two additional PLC isoforms were detected in ECs from PA and MCA. Co-expression of multiple PLC isoforms in ECs suggests an elaborate network of signalling pathways: PLC isoforms may contribute to the complexity or diversity of signalling by their selective localization in cellular microdomains. However in situ immunofluorescence revealed a homogeneous distribution for all PLC isoforms probed (β3, γ2 and δ1) in intact endothelium. Although PLC isoforms play a crucial role in endothelial signal transduction, subcellular localization alone does not appear to be sufficient to determine the role of PLC in the signalling microdomains found in the native endothelium.

  4. High-molecular weight Aβ oligomers and protofibrils are the predominant Aβ species in the native soluble protein fraction of the AD brain.

    PubMed

    Upadhaya, Ajeet Rijal; Lungrin, Irina; Yamaguchi, Haruyasu; Fändrich, Marcus; Thal, Dietmar Rudolf

    2012-02-01

    Alzheimer's disease (AD) is characterized by the aggregation and deposition of amyloid β protein (Aβ) in the brain. Soluble Aβ oligomers are thought to be toxic. To investigate the predominant species of Aβ protein that may play a role in AD pathogenesis, we performed biochemical analysis of AD and control brains. Sucrose buffer-soluble brain lysates were characterized in native form using blue native (BN)-PAGE and also in denatured form using SDS-PAGE followed by Western blot analysis. BN-PAGE analysis revealed a high-molecular weight smear (>1000 kD) of Aβ(42) -positive material in the AD brain, whereas low-molecular weight and monomeric Aβ species were not detected. SDS-PAGE analysis, on the other hand, allowed the detection of prominent Aβ monomer and dimer bands in AD cases but not in controls. Immunoelectron microscopy of immunoprecipitated oligomers and protofibrils/fibrils showed spherical and protofibrillar Aβ-positive material, thereby confirming the presence of high-molecular weight Aβ (hiMWAβ) aggregates in the AD brain. In vitro analysis of synthetic Aβ(40) - and Aβ(42) preparations revealed Aβ fibrils, protofibrils, and hiMWAβ oligomers that were detectable at the electron microscopic level and after BN-PAGE. Further, BN-PAGE analysis exhibited a monomer band and less prominent low-molecular weight Aβ (loMWAβ) oligomers. In contrast, SDS-PAGE showed large amounts of loMWAβ but no hiMWAβ(40) and strikingly reduced levels of hiMWAβ(42) . These results indicate that hiMWAβ aggregates, particularly Aβ(42) species, are most prevalent in the soluble fraction of the AD brain. Thus, soluble hiMWAβ aggregates may play an important role in the pathogenesis of AD either independently or as a reservoir for release of loMWAβ oligomers. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  5. Yeast prions are useful for studying protein chaperones and protein quality control.

    PubMed

    Masison, Daniel C; Reidy, Michael

    2015-01-01

    Protein chaperones help proteins adopt and maintain native conformations and play vital roles in cellular processes where proteins are partially folded. They comprise a major part of the cellular protein quality control system that protects the integrity of the proteome. Many disorders are caused when proteins misfold despite this protection. Yeast prions are fibrous amyloid aggregates of misfolded proteins. The normal action of chaperones on yeast prions breaks the fibers into pieces, which results in prion replication. Because this process is necessary for propagation of yeast prions, even small differences in activity of many chaperones noticeably affect prion phenotypes. Several other factors involved in protein processing also influence formation, propagation or elimination of prions in yeast. Thus, in much the same way that the dependency of viruses on cellular functions has allowed us to learn much about cell biology, the dependency of yeast prions on chaperones presents a unique and sensitive way to monitor the functions and interactions of many components of the cell's protein quality control system. Our recent work illustrates the utility of this system for identifying and defining chaperone machinery interactions.

  6. Draft De Novo Transcriptome of the Rat Kangaroo Potorous tridactylus as a Tool for Cell Biology

    PubMed Central

    Udy, Dylan B.; Voorhies, Mark; Chan, Patricia P.; Lowe, Todd M.; Dumont, Sophie

    2015-01-01

    The rat kangaroo (long-nosed potoroo, Potorous tridactylus) is a marsupial native to Australia. Cultured rat kangaroo kidney epithelial cells (PtK) are commonly used to study cell biological processes. These mammalian cells are large, adherent, and flat, and contain large and few chromosomes—and are thus ideal for imaging intra-cellular dynamics such as those of mitosis. Despite this, neither the rat kangaroo genome nor transcriptome have been sequenced, creating a challenge for probing the molecular basis of these cellular dynamics. Here, we present the sequencing, assembly and annotation of the draft rat kangaroo de novo transcriptome. We sequenced 679 million reads that mapped to 347,323 Trinity transcripts and 20,079 Unigenes. We present statistics emerging from transcriptome-wide analyses, and analyses suggesting that the transcriptome covers full-length sequences of most genes, many with multiple isoforms. We also validate our findings with a proof-of-concept gene knockdown experiment. We expect that this high quality transcriptome will make rat kangaroo cells a more tractable system for linking molecular-scale function and cellular-scale dynamics. PMID:26252667

  7. Draft De Novo Transcriptome of the Rat Kangaroo Potorous tridactylus as a Tool for Cell Biology.

    PubMed

    Udy, Dylan B; Voorhies, Mark; Chan, Patricia P; Lowe, Todd M; Dumont, Sophie

    2015-01-01

    The rat kangaroo (long-nosed potoroo, Potorous tridactylus) is a marsupial native to Australia. Cultured rat kangaroo kidney epithelial cells (PtK) are commonly used to study cell biological processes. These mammalian cells are large, adherent, and flat, and contain large and few chromosomes-and are thus ideal for imaging intra-cellular dynamics such as those of mitosis. Despite this, neither the rat kangaroo genome nor transcriptome have been sequenced, creating a challenge for probing the molecular basis of these cellular dynamics. Here, we present the sequencing, assembly and annotation of the draft rat kangaroo de novo transcriptome. We sequenced 679 million reads that mapped to 347,323 Trinity transcripts and 20,079 Unigenes. We present statistics emerging from transcriptome-wide analyses, and analyses suggesting that the transcriptome covers full-length sequences of most genes, many with multiple isoforms. We also validate our findings with a proof-of-concept gene knockdown experiment. We expect that this high quality transcriptome will make rat kangaroo cells a more tractable system for linking molecular-scale function and cellular-scale dynamics.

  8. Lipids, lysosomes, and autophagy

    PubMed Central

    2016-01-01

    Lipids are essential components of a cell providing energy substrates for cellular processes, signaling intermediates, and building blocks for biological membranes. Lipids are constantly recycled and redistributed within a cell. Lysosomes play an important role in this recycling process that involves the recruitment of lipids to lysosomes via autophagy or endocytosis for their degradation by lysosomal hydrolases. The catabolites produced are redistributed to various cellular compartments to support basic cellular function. Several studies demonstrated a bidirectional relationship between lipids and lysosomes that regulate autophagy. While lysosomal degradation pathways regulate cellular lipid metabolism, lipids also regulate lysosome function and autophagy. In this review, we focus on this bidirectional relationship in the context of dietary lipids and provide an overview of recent evidence of how lipid-overload lipotoxicity, as observed in obesity and metabolic syndrome, impairs lysosomal function and autophagy that may eventually lead to cellular dysfunction or cell death. PMID:27330054

  9. Cellular automaton formulation of passive scalar dynamics

    NASA Technical Reports Server (NTRS)

    Chen, Hudong; Matthaeus, William H.

    1987-01-01

    Cellular automata modeling of the advection of a passive scalar in a two-dimensional flow is examined in the context of discrete lattice kinetic theory. It is shown that if the passive scalar is represented by tagging or 'coloring' automation particles a passive advection-diffusion equation emerges without use of perturbation expansions. For the specific case of the hydrodynamic lattice gas model of Frisch et al. (1986), the diffusion coefficient is calculated by perturbation.

  10. Global analysis of bacterial transcription factors to predict cellular target processes.

    PubMed

    Doerks, Tobias; Andrade, Miguel A; Lathe, Warren; von Mering, Christian; Bork, Peer

    2004-03-01

    Whole-genome sequences are now available for >100 bacterial species, giving unprecedented power to comparative genomics approaches. We have applied genome-context methods to predict target processes that are regulated by transcription factors (TFs). Of 128 orthologous groups of proteins annotated as TFs, to date, 36 are functionally uncharacterized; in our analysis we predict a probable cellular target process or biochemical pathway for half of these functionally uncharacterized TFs.

  11. Combinatorial contextualization of peptidic epitopes for enhanced cellular immunity.

    PubMed

    Ito, Masaki; Hayashi, Kazumi; Adachi, Eru; Minamisawa, Tamiko; Homma, Sadamu; Koido, Shigeo; Shiba, Kiyotaka

    2014-01-01

    Invocation of cellular immunity by epitopic peptides remains largely dependent on empirically developed protocols, such as interfusion of aluminum salts or emulsification using terpenoids and surfactants. To explore novel vaccine formulation, epitopic peptide motifs were co-programmed with structural motifs to produce artificial antigens using our "motif-programming" approach. As a proof of concept, we used an ovalbumin (OVA) system and prepared an artificial protein library by combinatorially polymerizing MHC class I and II sequences from OVA along with a sequence that tends to form secondary structures. The purified endotoxin-free proteins were then examined for their ability to activate OVA-specific T-cell hybridoma cells after being processed within dendritic cells. One clone, F37A (containing three MHC I and two MHC II OVA epitopes), possessed a greater ability to evoke cellular immunity than the native OVA or the other artificial antigens. The sensitivity profiles of drugs that interfered with the F37A uptake differed from those of the other artificial proteins and OVA, suggesting that alteration of the cross-presentation pathway is responsible for the enhanced immunogenicity. Moreover, F37A, but not an epitopic peptide, invoked cellular immunity when injected together with monophosphoryl lipid A (MPL), and retarded tumor growth in mice. Thus, an artificially synthesized protein antigen induced cellular immunity in vivo in the absence of incomplete Freund's adjuvant or aluminum salts. The method described here could be potentially used for developing vaccines for such intractable ailments as AIDS, malaria and cancer, ailments in which cellular immunity likely play a crucial role in prevention and treatment.

  12. Strategies and Struggles in the ELT Classroom: Language Policy, Learner Autonomy, and Innovative Practice

    ERIC Educational Resources Information Center

    Rivers, Damian J.

    2011-01-01

    Within the Japanese English Language Teaching context and consistent with the dominant conversation role assigned to the native English speaker teacher, there exists a belief that the most effective manner in which to teach and promote multilingualism and intercultural understanding is through restricting students to monolingual practices and…

  13. Inter-Industry Wage Differentials and the Gender Wage Gap: An Identification Problem.

    ERIC Educational Resources Information Center

    Horrace, William C.; Oaxaca, Ronald L.

    2001-01-01

    States that a method for estimating gender wage gaps by industry yields estimates that vary according to arbitrary choice of omitted reference groups. Suggests alternative methods not susceptible to this problem that can be applied to other contexts, such as racial, union/nonunion, and immigrant/native wage differences. (SK)

  14. Does the New Digital Generation of Learners Exist? A Qualitative Study

    ERIC Educational Resources Information Center

    Sanchez, Jaime; Salinas, Alvaro; Contreras, David; Meyer, Eduardo

    2011-01-01

    This paper seeks to contribute to the discussion on the current generation of students and their relationship to technology, providing qualitative, empirical information obtained in the Chilean context. The study analyses and discusses the ideas regarding the emergence of a new generation of learners, or digital natives, as characterised by…

  15. Students' and Teachers' Ideals of Effective Business English Teaching

    ERIC Educational Resources Information Center

    Trinder, Ruth; Herles, Martin

    2013-01-01

    Learners' and teachers' evaluation of what constitutes useful, appropriate, and goal-relevant English may well shift in view of the globalization of English and its dominance in non-native contexts, business, and new media. Against this background, this study explores the extent to which a specific Business English university programme meets…

  16. Emotion Knowledge and Autobiographical Memory across the Preschool Years: A Cross-Cultural Longitudinal Investigation

    ERIC Educational Resources Information Center

    Wang, Qi

    2008-01-01

    Knowledge of emotion situations facilitates the interpretation, processing, and organization of significant personal event information and thus may be an important contributor to the development of autobiographical memory. This longitudinal study tested the hypothesis in a cross-cultural context. The participants were native Chinese children,…

  17. Analysis of the Problems of the Chinese College Students' EFL Classroom Writings

    ERIC Educational Resources Information Center

    Yu, Aiju

    2012-01-01

    This paper explores the problems of EFL classroom writings in the Chinese college teaching context from the perspective of textual organization and pragmatic strategy. Influence of their native cultural thought pattern causes the problem of discourse pattern and cohesion; lack of sufficient pragmatic strategy renders students' unawareness in…

  18. Ariadne's Thread and Indra's Net: Reflections on Ethnography, Ethnicity, Identity, Culture, and Interaction.

    ERIC Educational Resources Information Center

    Moerman, Michael

    1993-01-01

    Defines and illustrates the main tools used in intercultural research: ethnography, ethnicity, social interaction, identity, and culture. These are the ongoing product of intersecting processes. All are social accomplishments, influenced by the context in which they occur. The anthropologist and native jointly participate in these enterprises. (17…

  19. English Speakers Attend More Strongly than Spanish Speakers to Manner of Motion when Classifying Novel Objects and Events

    ERIC Educational Resources Information Center

    Kersten, Alan W.; Meissner, Christian A.; Lechuga, Julia; Schwartz, Bennett L.; Albrechtsen, Justin S.; Iglesias, Adam

    2010-01-01

    Three experiments provide evidence that the conceptualization of moving objects and events is influenced by one's native language, consistent with linguistic relativity theory. Monolingual English speakers and bilingual Spanish/English speakers tested in an English-speaking context performed better than monolingual Spanish speakers and bilingual…

  20. In Search of the Right Questions: Language Background Profiling at Ontario Public Schools

    ERIC Educational Resources Information Center

    Slavkov, Nikolay

    2016-01-01

    This article examines some of the challenges that the notion of a (monolingual) native speaker faces in a global context of increasing awareness that bilingualism and multilingualism are the norm rather than the exception. It also discusses the distinction between two child language acquisition environments, bilingual first language acquisition…

  1. Context Effects in the Processing of Phonolexical Ambiguity in L2

    ERIC Educational Resources Information Center

    Chrabaszcz, Anna; Gor, Kira

    2014-01-01

    In order to comprehend speech, listeners have to combine low-level phonetic information about the incoming auditory signal with higher-order contextual information to make a lexical selection. This requires stable phonological categories and unambiguous representations of words in the mental lexicon. Unlike native speakers, second language (L2)…

  2. Catholic Schools and Immigrant Students: A New Generation

    ERIC Educational Resources Information Center

    Louie, Vivian; Holdaway, Jennifer

    2009-01-01

    Background/Context: This article considers the role of Catholic schools, an institution born of the adaptation of previous immigrant waves, in the education of new immigrants and their native-born counterparts. The new immigrants enter a landscape in which education plays a much bigger role than it did for their predecessors and yet faces many…

  3. Spoken Grammar: An Urgent Necessity in the EFL Context

    ERIC Educational Resources Information Center

    Al-wossabi, Sami A.

    2014-01-01

    Recent studies in corpus linguistics have revealed apparent inconsistencies between the prescriptive grammar presented in EFL textbooks and the type of grammar used in the speech of native speakers. Such variations and learning gaps deprive EFL learners of the actual use of English and delay their oral/aural developmental processes. The focus of…

  4. Second- and Foreign-Language Variation in Tense Backshifting in Indirect Reported Speech

    ERIC Educational Resources Information Center

    Charkova, Krassimira D.; Halliday, Laura J.

    2011-01-01

    This study examined how English learners in second-language (SL) and foreign-language (FL) contexts employ tense backshifting in indirect reported speech. Participants included 35 international students in the United States, 37 Bulgarian speakers of English, 38 Bosnian speakers of English, and 41 native English speakers. The instrument involved…

  5. Forest restoration in a global context

    Treesearch

    John A. Stanturf

    2000-01-01

    Forest restoration on land cleared for agriculture is occurring around the world. Often land was abandoned because of infertility, frequent flooding, or other site limitations. In some countries, market forces or changing trade policies drive conversion of cleared land to plantations of exotic or native tree species. The objective of this paper is to introduce the...

  6. "Technological Me": Young Children's Use of Technology across Their Home and School Contexts

    ERIC Educational Resources Information Center

    Gronn, Donna; Scott, Anne; Edwards, Susan; Henderson, Michael

    2014-01-01

    Research into children's learning with digital technologies is represented by a growing body of literature examining the relationship between home-school technological practices. A focus of this work is on the notion of a "digital-disconnect" between home and school. This argument suggests that children are such native users of…

  7. Culture, Context, and the Internalizing Distress of Mexican American Youth

    ERIC Educational Resources Information Center

    Polo, Antonio J.; Lopez, Steven R.

    2009-01-01

    Latino youth appear to be at higher risk for depression relative to youth from other ethnic groups. This study assessed the relationship between nativity and several forms of internalizing distress among Mexican American middle school students as well as sociocultural factors that may help explain this relationship. Immigrant Mexican American…

  8. Influence of Sociocultural Context on Language Learning in Foreign Countries

    ERIC Educational Resources Information Center

    Pazyura, Natalia

    2016-01-01

    Professional foreign language training is offered to cultivate the ability to master cross-cultural communication in the sphere of future professional activity. By means of intercultural competence of foreign language we are raising professional competence, too. In countries where English is the native language, it is taught to speakers of other…

  9. Identifying Rural Health Care Needs Using Community Conversations

    ERIC Educational Resources Information Center

    Moulton, Patricia L.; Miller, Marlene E.; Offutt, Sue M.; Gibbens, Brad P.

    2007-01-01

    Context: Community input can lead to better-defined goals in an organization. With this in mind, the Center for Rural Health at the University of North Dakota School of Medicine and Health Sciences embarked on a series of 13 meetings with representatives of organizations serving rural communities, including 5 Native American reservations. Purpose:…

  10. EFL Learner's Awareness of Stress-Moving vs. Neutral Suffixes

    ERIC Educational Resources Information Center

    Shemshadsara, Zahra Ghorbani

    2011-01-01

    Mastering pronunciation in EFL context, where direct access to native speaker is scarce, is a highly challenging objective for many language students in Iran. Stress as a suprasegmental feature, more specifically, poses its own problems, specially when suffixes are added to words. There are different types of suffixes, two of which are neutral…

  11. Functions of Turkish Complementary Schools in the UK: Official vs. Insider Discourses

    ERIC Educational Resources Information Center

    Çavusoglu, Çise

    2014-01-01

    Complementary schools in the United Kingdom (UK) are community organised schools with the general aim of teaching younger generations their "native" languages and cultures. However, the aims and practices of these schools are predominantly dependent on changes in the social and political contexts both in the host country (in this case…

  12. Investigating the Impacts of an Experiential Service-Learning Course

    ERIC Educational Resources Information Center

    Kassabgy, Nagwa; El-Din, Yasmine Salah

    2013-01-01

    This study investigated the impacts of an undergraduate experiential service-learning course on the development, attitudes, and perceptions of the co-learners involved in the experience. The context of the study was the American University in Cairo (AUC), and the participants in both groups were Egyptian native speakers of Arabic. The participants…

  13. The Cora: People of the Sierra Madre.

    ERIC Educational Resources Information Center

    Lane, Sarah; And Others

    This text explores an isolated and indigenous people who live in the Sierra Madre Occidental in Mexico. Isolation has allowed the Cora Indians to maintain their traditional customs to a much greater extent than many other groups of Native Americans. The historical and geographical contexts of the Cora are presented in this curriculum resource.…

  14. Children Environmental Identity Development in an Alaska Native Rural Context

    ERIC Educational Resources Information Center

    Green, Carie

    2017-01-01

    Scholarship in Early Childhood Education for Sustainability (ECEfS) continues to advocate for the incorporation of Indigenous ways of knowing and children's agency in research and practice. This study contributes to the literature by examining how young children from an Alaskan rural setting make meaning of and interact with nature. Informed by a…

  15. Preparedness for eHealth: Health Sciences Students' Knowledge, Skills, and Confidence

    ERIC Educational Resources Information Center

    Lam, Mary K.; Hines, Monique; Lowe, Robyn; Nagarajan, Srivalli; Keep, Melanie; Penman, Merrolee; Power, Emma

    2016-01-01

    There is increasing recognition of the role eHealth will play in the effective and efficient delivery of healthcare. This research challenges the assumption that students enter university as digital natives, able to confidently and competently adapt their use of information and communication technology (ICT) to new contexts. This study explored…

  16. Verbal Interaction in "Second Life": Towards a Pedagogic Framework for Task Design

    ERIC Educational Resources Information Center

    Jauregi, Kristi; Canto, Silvia; de Graaff, Rick; Koenraad, Ton; Moonen, Machteld

    2011-01-01

    Within a European project on Networked Interaction in Foreign Language Acquisition and Research (NIFLAR), "Second Life" was used as a 3D virtual world in which language students can communicate synchronously with native speakers in the target language, while undertaking action together. For this context, a set of design principles for…

  17. Three Fundamental Concepts in Second Language Acquisition and Their Relevance in Multilingual Contexts

    ERIC Educational Resources Information Center

    Kramsch, Claire; Whiteside, Anne

    2007-01-01

    This article considers how 3 fundamental concepts of second language acquisition (SLA), the native speaker, interlanguage, and the language learner have fared since Firth and Wagner (1997). We review the ascendancy of these concepts and their relationship to the traditional dichotomies of language learning versus language use and individual mind…

  18. Dostoyevsky and Europe. A Secondary Education for Europe.

    ERIC Educational Resources Information Center

    Dalipagic-Czimazia, Catherine

    The overarching theme of this monograph is how a Russian intellectual, Fyodor Dostoyevsky, saw himself in the European context. By reference to various of Fyodor Dostoyevsky's romanesque works, the monograph proposes an account of the development of the European awareness of an author nevertheless greatly attached to his native land, and of his…

  19. Poorer Phonetic Perceivers Show Greater Benefit in Phonetic-Phonological Speech Learning

    ERIC Educational Resources Information Center

    Ingvalson, Erin M.; Barr, Allison M.; Wong, Patrick C. M.

    2013-01-01

    Purpose: Previous research has demonstrated that native English speakers can learn lexical tones in word context (pitch-to-word learning), to an extent. However, learning success depends on learners' pre-training sensitivity to pitch patterns. The aim of this study was to determine whether lexical pitch-pattern training given before lexical…

  20. Chinese-French Case Study of English Language Learning via Wikispaces, Animoto and Skype

    ERIC Educational Resources Information Center

    Hartwell, Laura M.; Zou, Bin

    2013-01-01

    This paper reports on the learning experience of Chinese and French students participating in a computer mediated communication (CMC) collaboration conducted in English and supported by Wikispaces, Animoto, and Skype. Several studies have investigated CMC contexts in which at least some participants were native speakers. Here, we address the…

  1. More than One Mask: The Context of NAGPRA for Museums and Tribes

    ERIC Educational Resources Information Center

    Luby, Edward M.; Nelson, Melissa K.

    2008-01-01

    The Native American Graves Protection and Repatriation Act (NAGPRA) has fundamentally changed the relationship between museums and tribal peoples. Since 1990, thousands of human remains and funerary objects and hundreds of sacred objects and objects of cultural patrimony have been repatriated to tribes. Human remains and funerary objects have been…

  2. Indigenous Knowledge as a Tool for Self-Determination and Liberation.

    ERIC Educational Resources Information Center

    Hill, Dawn Martin

    This paper explores aspects of Indigenous knowledge on several levels and examines the role of Indigenous knowledge in Indigenous empowerment as the number and influence of Native people in academia increases. Indigenous peoples worldwide have a common set of assumptions that forms a context or paradigm--a collective core of interrelated…

  3. The Political Capital of Trustees and Stakeholder Satisfaction at Four Tribal Colleges and Universities

    ERIC Educational Resources Information Center

    Phillips, John L.

    2005-01-01

    Why are some tribal organizations more effective than others? Does political capital--connections, influence and power--enable or constrain the ability of a tribal organization to work successfully within its Native community? This paper explores these questions within the context of American Indian higher education by using political capital…

  4. Planning a native plant nursery [Chapter 1

    Treesearch

    Kim M. Wilkinson; Thomas D. Landis

    2009-01-01

    Every nursery is unique. The environmental, social, and economic context is different for each nursery. A wide variety of species and outplanting environments contributes to nursery diversity. In addition, each nursery has a distinct vision and purpose.The methods a nursery will use to bring people together, produce high-quality plants for the community, and share...

  5. Lexical Inferencing in First and Second Language Listening

    ERIC Educational Resources Information Center

    Van Zeeland, Hilde

    2014-01-01

    Lexical inferencing is an important vocabulary learning strategy. Unfortunately, almost all research on this issue has been carried out in the reading context. This study is the first to directly measure lexical inferencing success in listening, by both native (N?=?47) and nonnative (N?=?30) speakers of English. It analysed the effects of…

  6. "In the End, Our Message Weighs": "Blood Run," NAGPRA, and American Indian Identity

    ERIC Educational Resources Information Center

    Kelsey, Penelope; Carpenter, Cari M.

    2011-01-01

    In this article, the authors juxtapose Allison Hedge Coke's poetry collection "Blood Run" (2006) with the larger context in which Native American Graves Protection and Repatriation Act (NAGPRA) operates in order to investigate how "Blood Run" exposes the limitations of repatriation legislation, most significantly, how NAGPRA's…

  7. Vocabulary Learning in Massively Multiplayer Online Games: Context and Action before Words

    ERIC Educational Resources Information Center

    Zheng, Dongping; Bischoff, Michael; Gilliland, Betsy

    2015-01-01

    Drawing on ecological and dialogical perspectives on language and cognition, this exploratory case study examines how vocabulary learning occurs during a quest-play mediated in English between a Japanese undergraduate student and a native speaker of English. Understanding embodiment as coaction between the player-avatar and player-player relations…

  8. Variation in tussock traits of the invasive cordgrass Spartina densiflora along the Pacific Coast of North America

    USDA-ARS?s Scientific Manuscript database

    Some introduced species rapidly spread to cover large novel habitats beyond their native range mediated by a high degree of phenotypic plasticity and/or rapid evolutionary responses. In this context, clonality has been described as a significant factor contributing to invasiveness. We studied the ab...

  9. Telecollaboration in Online Communities for L2 Learning

    ERIC Educational Resources Information Center

    Malerba, Maria Luisa; Appel, Christine

    2016-01-01

    This paper reports on a PhD study about informal second language learning in online communities (Livemocha and Busuu). In these communities learners autonomously seek opportunities for telecollaboration with Native Speakers (NSs) in the absence of teachers and pedagogical tasks, and in an informal context. This paper focuses on learning and social…

  10. Two languages, two personalities? Examining language effects on the expression of personality in a bilingual context.

    PubMed

    Chen, Sylvia Xiaohua; Bond, Michael Harris

    2010-11-01

    The issue of whether personality changes as a function of language is controversial. The present research tested the cultural accommodation hypothesis by examining the impact of language use on personality as perceived by the self and by others. In Study 1, Hong Kong Chinese-English bilinguals responded to personality inventories in Chinese or English on perceived traits for themselves, typical native speakers of Chinese, and typical native speakers of English. Study 2 adopted a repeated measures design and collected data at three time points from written measures and actual conversations to examine whether bilinguals exhibited different patterns of personality, each associated with one of their two languages and the ethnicity of their interlocutors. Self-reports and behavioral observations confirmed the effects of perceived cultural norms, language priming, and interlocutor ethnicity on various personality dimensions. It is suggested that use of a second language accesses the perceived cultural norms of the group most associated with that language, especially its prototypic trait profiles, thus activating behavioral expressions of personality that are appropriate in the corresponding linguistic-social context.

  11. Learning-Based Research: The Re-Integration of Learning Styles into STEM Research Through the Context of Solar Energy and Climate Literacy

    NASA Astrophysics Data System (ADS)

    Bosman, L.

    2014-12-01

    This presentation will provide an overview of a NASA NICE-T funded research project at the College of Menominee Nation, a small federally recognized Tribal College located in northern Wisconsin. One main objective of the research project is to provide an experiential learning opportunity for 4-6 STEM students to construct a user friendly solar energy system evaluation tool, incorporating the real-world performance of different solar modules at Argonne National Laboratory, NASA weather and solar irradiation data, and detailed cost analysis and investment payback period. A natural connection exists between Native Americans and renewable energy. The generally clean character of renewable energies provides a great synergy and complimentary attribute for Native Americans' respect and pride for the environment and the overarching concern for future generations (Council, Pierce et al. 2000). Furthermore, Native American cultures have a strong creative and artistic focus, often motivated by their respect and appreciation for nature. The purpose of this learning-based research is to apply a cross-disciplinary approach to integrate the humanities with STEM research within the context of solar energy and climate literacy. Using 7 different learning styles (visual, aural, verbal, physical, logical, social, and solitary), students have the opportunity to showcase their research efforts through a variety of modes and artifacts including graphic novel development (Visual), spoken word poetry (Aural), conference presentation (Verbal), experiential display and demonstration (Physical), debate (Logical), social media and viral messaging (Social), and article submission (Solitary).

  12. A first line of stress defense: small heat shock proteins and their function in protein homeostasis.

    PubMed

    Haslbeck, Martin; Vierling, Elizabeth

    2015-04-10

    Small heat shock proteins (sHsps) are virtually ubiquitous molecular chaperones that can prevent the irreversible aggregation of denaturing proteins. sHsps complex with a variety of non-native proteins in an ATP-independent manner and, in the context of the stress response, form a first line of defense against protein aggregation in order to maintain protein homeostasis. In vertebrates, they act to maintain the clarity of the eye lens, and in humans, sHsp mutations are linked to myopathies and neuropathies. Although found in all domains of life, sHsps are quite diverse and have evolved independently in metazoans, plants and fungi. sHsp monomers range in size from approximately 12 to 42kDa and are defined by a conserved β-sandwich α-crystallin domain, flanked by variable N- and C-terminal sequences. Most sHsps form large oligomeric ensembles with a broad distribution of different, sphere- or barrel-like oligomers, with the size and structure of the oligomers dictated by features of the N- and C-termini. The activity of sHsps is regulated by mechanisms that change the equilibrium distribution in tertiary features and/or quaternary structure of the sHsp ensembles. Cooperation and/or co-assembly between different sHsps in the same cellular compartment add an underexplored level of complexity to sHsp structure and function. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Chromatin immunoprecipitation assays: application of ChIP-on-chip for defining dynamic transcriptional mechanisms in bone cells.

    PubMed

    van der Deen, Margaretha; Hassan, Mohammad Q; Pratap, Jitesh; Teplyuk, Nadiya M; Young, Daniel W; Javed, Amjad; Zaidi, Sayyed K; Lian, Jane B; Montecino, Martin; Stein, Janet L; Stein, Gary S; van Wijnen, Andre J

    2008-01-01

    Normal cell growth and differentiation of bone cells requires the sequential expression of cell type specific genes to permit lineage specification and development of cellular phenotypes. Transcriptional activation and repression of distinct sets of genes support the anabolic functions of osteoblasts and the catabolic properties of osteoclasts. Furthermore, metastasis of tumors to the bone environment is controlled by transcriptional mechanisms. Insights into the transcriptional regulation of genes in bone cells may provide a conceptual basis for improved therapeutic approaches to treat bone fractures, genetic osteopathologies, and/or cancer metastases to bone. Chromatin immunoprecipitation (ChIP) is a powerful technique to establish in vivo binding of transcription factors to the promoters of genes that are either activated or repressed in bone cells. Combining ChIP with genomic microarray analysis, colloquially referred to as "ChIP-on-chip," has become a valuable method for analysis of endogenous protein/DNA interactions. This technique permits assessment of chromosomal binding sites for transcription factors or the location of histone modifications at a genomic scale. This chapter discusses protocols for performing chromatin immunoprecipitation experiments, with a focus on ChIP-on-chip analysis. The information presented is based on the authors' experience with defining interactions of Runt-related (RUNX) transcription factors with bone-related genes within the context of the native nucleosomal organization of intact osteoblastic cells.

  14. β-Helical architecture of cytoskeletal bactofilin filaments revealed by solid-state NMR

    PubMed Central

    Vasa, Suresh; Lin, Lin; Shi, Chaowei; Habenstein, Birgit; Riedel, Dietmar; Kühn, Juliane; Thanbichler, Martin; Lange, Adam

    2015-01-01

    Bactofilins are a widespread class of bacterial filament-forming proteins, which serve as cytoskeletal scaffolds in various cellular pathways. They are characterized by a conserved architecture, featuring a central conserved domain (DUF583) that is flanked by variable terminal regions. Here, we present a detailed investigation of bactofilin filaments from Caulobacter crescentus by high-resolution solid-state NMR spectroscopy. De novo sequential resonance assignments were obtained for residues Ala39 to Phe137, spanning the conserved DUF583 domain. Analysis of the secondary chemical shifts shows that this core region adopts predominantly β-sheet secondary structure. Mutational studies of conserved hydrophobic residues located in the identified β-strand segments suggest that bactofilin folding and polymerization is mediated by an extensive and redundant network of hydrophobic interactions, consistent with the high intrinsic stability of bactofilin polymers. Transmission electron microscopy revealed a propensity of bactofilin to form filament bundles as well as sheet-like, 2D crystalline assemblies, which may represent the supramolecular arrangement of bactofilin in the native context. Based on the diffraction pattern of these 2D crystalline assemblies, scanning transmission electron microscopy measurements of the mass per length of BacA filaments, and the distribution of β-strand segments identified by solid-state NMR, we propose that the DUF583 domain adopts a β-helical architecture, in which 18 β-strand segments are arranged in six consecutive windings of a β-helix. PMID:25550503

  15. β-Helical architecture of cytoskeletal bactofilin filaments revealed by solid-state NMR.

    PubMed

    Vasa, Suresh; Lin, Lin; Shi, Chaowei; Habenstein, Birgit; Riedel, Dietmar; Kühn, Juliane; Thanbichler, Martin; Lange, Adam

    2015-01-13

    Bactofilins are a widespread class of bacterial filament-forming proteins, which serve as cytoskeletal scaffolds in various cellular pathways. They are characterized by a conserved architecture, featuring a central conserved domain (DUF583) that is flanked by variable terminal regions. Here, we present a detailed investigation of bactofilin filaments from Caulobacter crescentus by high-resolution solid-state NMR spectroscopy. De novo sequential resonance assignments were obtained for residues Ala39 to Phe137, spanning the conserved DUF583 domain. Analysis of the secondary chemical shifts shows that this core region adopts predominantly β-sheet secondary structure. Mutational studies of conserved hydrophobic residues located in the identified β-strand segments suggest that bactofilin folding and polymerization is mediated by an extensive and redundant network of hydrophobic interactions, consistent with the high intrinsic stability of bactofilin polymers. Transmission electron microscopy revealed a propensity of bactofilin to form filament bundles as well as sheet-like, 2D crystalline assemblies, which may represent the supramolecular arrangement of bactofilin in the native context. Based on the diffraction pattern of these 2D crystalline assemblies, scanning transmission electron microscopy measurements of the mass per length of BacA filaments, and the distribution of β-strand segments identified by solid-state NMR, we propose that the DUF583 domain adopts a β-helical architecture, in which 18 β-strand segments are arranged in six consecutive windings of a β-helix.

  16. Transforming growth factor alpha, Shope fibroma growth factor, and vaccinia growth factor can replace myxoma growth factor in the induction of myxomatosis in rabbits.

    PubMed

    Opgenorth, A; Nation, N; Graham, K; McFadden, G

    1993-02-01

    The epidermal growth factor (EGF) homologues encoded by vaccinia virus, myxoma virus, and malignant rabbit fibroma virus have been shown to contribute to the pathogenicity of virus infection upon inoculation of susceptible hosts. However, since the primary structures of these growth factors and the disease profiles induced by different poxvirus genera vary substantially, the degree to which the various EGF homologues perform similar roles in viral pathogenesis remains unclear. In order to determine whether different EGF-like growth factors can perform qualitatively similar functions in the induction of myxomatosis in rabbits, we created recombinant myxoma virus variants in which the native growth factor, myxoma growth factor (MGF), was disrupted and replaced with either vaccinia virus growth factor, Shope fibroma growth factor, or rat transforming growth factor alpha. Unlike the control virus containing an inactivated MGF gene, which caused marked attenuation of the disease syndrome and substantially less proliferation of the epithelial cell layers in the conjunctiva and respiratory tract, the recombinant myxoma virus strains expressing heterologous growth factors produced infections which were both clinically and histopathologically indistinguishable from wild-type myxomatosis. We conclude that these poxviral and cellular EGF-like growth factors, which are diverse with respect to primary structure and origin, have similar biological functions in the context of myxoma virus pathogenesis and are mitogenic for the same target cells.

  17. Survey statistics of automated segmentations applied to optical imaging of mammalian cells.

    PubMed

    Bajcsy, Peter; Cardone, Antonio; Chalfoun, Joe; Halter, Michael; Juba, Derek; Kociolek, Marcin; Majurski, Michael; Peskin, Adele; Simon, Carl; Simon, Mylene; Vandecreme, Antoine; Brady, Mary

    2015-10-15

    The goal of this survey paper is to overview cellular measurements using optical microscopy imaging followed by automated image segmentation. The cellular measurements of primary interest are taken from mammalian cells and their components. They are denoted as two- or three-dimensional (2D or 3D) image objects of biological interest. In our applications, such cellular measurements are important for understanding cell phenomena, such as cell counts, cell-scaffold interactions, cell colony growth rates, or cell pluripotency stability, as well as for establishing quality metrics for stem cell therapies. In this context, this survey paper is focused on automated segmentation as a software-based measurement leading to quantitative cellular measurements. We define the scope of this survey and a classification schema first. Next, all found and manually filteredpublications are classified according to the main categories: (1) objects of interests (or objects to be segmented), (2) imaging modalities, (3) digital data axes, (4) segmentation algorithms, (5) segmentation evaluations, (6) computational hardware platforms used for segmentation acceleration, and (7) object (cellular) measurements. Finally, all classified papers are converted programmatically into a set of hyperlinked web pages with occurrence and co-occurrence statistics of assigned categories. The survey paper presents to a reader: (a) the state-of-the-art overview of published papers about automated segmentation applied to optical microscopy imaging of mammalian cells, (b) a classification of segmentation aspects in the context of cell optical imaging, (c) histogram and co-occurrence summary statistics about cellular measurements, segmentations, segmented objects, segmentation evaluations, and the use of computational platforms for accelerating segmentation execution, and (d) open research problems to pursue. The novel contributions of this survey paper are: (1) a new type of classification of cellular measurements and automated segmentation, (2) statistics about the published literature, and (3) a web hyperlinked interface to classification statistics of the surveyed papers at https://isg.nist.gov/deepzoomweb/resources/survey/index.html.

  18. Structural Interface Parameters Are Discriminatory in Recognising Near-Native Poses of Protein-Protein Interactions

    PubMed Central

    Malhotra, Sony; Sankar, Kannan; Sowdhamini, Ramanathan

    2014-01-01

    Interactions at the molecular level in the cellular environment play a very crucial role in maintaining the physiological functioning of the cell. These molecular interactions exist at varied levels viz. protein-protein interactions, protein-nucleic acid interactions or protein-small molecules interactions. Presently in the field, these interactions and their mechanisms mark intensively studied areas. Molecular interactions can also be studied computationally using the approach named as Molecular Docking. Molecular docking employs search algorithms to predict the possible conformations for interacting partners and then calculates interaction energies. However, docking proposes number of solutions as different docked poses and hence offers a serious challenge to identify the native (or near native) structures from the pool of these docked poses. Here, we propose a rigorous scoring scheme called DockScore which can be used to rank the docked poses and identify the best docked pose out of many as proposed by docking algorithm employed. The scoring identifies the optimal interactions between the two protein partners utilising various features of the putative interface like area, short contacts, conservation, spatial clustering and the presence of positively charged and hydrophobic residues. DockScore was first trained on a set of 30 protein-protein complexes to determine the weights for different parameters. Subsequently, we tested the scoring scheme on 30 different protein-protein complexes and native or near-native structure were assigned the top rank from a pool of docked poses in 26 of the tested cases. We tested the ability of DockScore to discriminate likely dimer interactions that differ substantially within a homologous family and also demonstrate that DOCKSCORE can distinguish correct pose for all 10 recent CAPRI targets. PMID:24498255

  19. Structural interface parameters are discriminatory in recognising near-native poses of protein-protein interactions.

    PubMed

    Malhotra, Sony; Sankar, Kannan; Sowdhamini, Ramanathan

    2014-01-01

    Interactions at the molecular level in the cellular environment play a very crucial role in maintaining the physiological functioning of the cell. These molecular interactions exist at varied levels viz. protein-protein interactions, protein-nucleic acid interactions or protein-small molecules interactions. Presently in the field, these interactions and their mechanisms mark intensively studied areas. Molecular interactions can also be studied computationally using the approach named as Molecular Docking. Molecular docking employs search algorithms to predict the possible conformations for interacting partners and then calculates interaction energies. However, docking proposes number of solutions as different docked poses and hence offers a serious challenge to identify the native (or near native) structures from the pool of these docked poses. Here, we propose a rigorous scoring scheme called DockScore which can be used to rank the docked poses and identify the best docked pose out of many as proposed by docking algorithm employed. The scoring identifies the optimal interactions between the two protein partners utilising various features of the putative interface like area, short contacts, conservation, spatial clustering and the presence of positively charged and hydrophobic residues. DockScore was first trained on a set of 30 protein-protein complexes to determine the weights for different parameters. Subsequently, we tested the scoring scheme on 30 different protein-protein complexes and native or near-native structure were assigned the top rank from a pool of docked poses in 26 of the tested cases. We tested the ability of DockScore to discriminate likely dimer interactions that differ substantially within a homologous family and also demonstrate that DOCKSCORE can distinguish correct pose for all 10 recent CAPRI targets.

  20. Proteomic analysis highlights the molecular complexities of native Kv4 channel macromolecular complexes.

    PubMed

    Marionneau, Céline; Townsend, R Reid; Nerbonne, Jeanne M

    2011-04-01

    Voltage-gated K(+) (Kv) channels are key determinants of membrane excitability in the nervous and cardiovascular systems, functioning to control resting membrane potentials, shape action potential waveforms and influence the responses to neurotransmitters and neurohormones. Consistent with this functional diversity, multiple types of Kv currents, with distinct biophysical properties and cellular/subcellular distributions, have been identified. Rapidly activating and inactivating Kv currents, typically referred to as I(A) (A-type) in neurons, for example, regulate repetitive firing rates, action potential back-propagation (into dendrites) and modulate synaptic responses. Currents with similar properties, referred to as I(to,f) (fast transient outward), expressed in cardiomyocytes, control the early phase of myocardial action potential repolarization. A number of studies have demonstrated critical roles for pore-forming (α) subunits of the Kv4 subfamily in the generation of native neuronal I(A) and cardiac I(to,f) channels. Studies in heterologous cells have also suggested important roles for a number of Kv channel accessory and regulatory proteins in the generation of functional I(A) and I(to,f) channels. Quantitative mass spectrometry-based proteomic analysis is increasingly recognized as a rapid and, importantly, unbiased, approach to identify the components of native macromolecular protein complexes. The recent application of proteomic approaches to identify the components of native neuronal (and cardiac) Kv4 channel complexes has revealed even greater complexity than anticipated. The continued emphasis on development of improved biochemical and analytical proteomic methods seems certain to accelerate progress and to provide important new insights into the molecular determinants of native ion channel protein complexes. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Crossing boundaries: the importance of cellular membranes in industrial biotechnology.

    PubMed

    Jezierska, Sylwia; Van Bogaert, Inge N A

    2017-05-01

    How small molecules cross cellular membranes is an often overlooked issue in an industrial microbiology and biotechnology context. This is to a large extent governed by the technical difficulties to study these transport systems or by the lack of knowledge on suitable efflux pumps. This review emphasizes the importance of microbial cellular membranes in industrial biotechnology by highlighting successful strategies of membrane engineering towards more resistant and hence better performing microorganisms, as well as transporter and other engineering strategies for increased efflux of primary and secondary metabolites. Furthermore, the benefits and limitations of eukaryotic subcellular compartmentalization are discussed, as well as the biotechnological potential of membrane vesicles.

  2. Two sides of a coin: Effects of climate change on the native and non-native distribution of Colossoma macropomum in South America.

    PubMed

    Lopes, Taise M; Bailly, Dayani; Almeida, Bia A; Santos, Natália C L; Gimenez, Barbara C G; Landgraf, Guilherme O; Sales, Paulo C L; Lima-Ribeiro, Matheus S; Cassemiro, Fernanda A S; Rangel, Thiago F; Diniz-Filho, José A F; Agostinho, Angelo A; Gomes, Luiz C

    2017-01-01

    Climate change and species invasions interact in nature, disrupting biological communities. Based on this knowledge, we simultaneously assessed the effects of climate change on the native distribution of the Amazonian fish Colossoma macropomum as well as on its invasiveness across river basins of South America, using ecological niche modeling. We used six niche models within the ensemble forecast context to predict the geographical distribution of C. macropomum for the present time, 2050 and 2080. Given that this species has been continuously introduced into non-native South American basins by fish farming activities, we added the locations of C. macropomum farms into the modeling process to obtain a more realistic scenario of its invasive potential. Based on modelling outputs we mapped climate refuge areas at different times. Our results showed that a plenty of climatically suitable areas for the occurrence of C. macropomum occurrence are located outside the original basins at the present time and that its invasive potential is greatly amplified by fish farms. Simulations of future geographic ranges revealed drastic range contraction in the native region, implying concerns not only with respect to the species conservation but also from a socio-economic perspective since the species is a cornerstone of artisanal and commercial fisheries in the Amazon. Although the invasive potential is projected to decrease in the face of climate change, climate refugia will concentrate in Paraná River, Southeast Atlantic and East Atlantic basins, putting intense, negative pressures on the native fish fauna these regions. Our findings show that short and long-term management actions are required for: i) the conservation of natural stocks of C. macropomum in the Amazon, and ii) protecting native fish fauna in the climate refuges of the invaded regions.

  3. Low Predictability of Colour Polymorphism in Introduced Guppy (Poecilia reticulata) Populations in Panama

    PubMed Central

    Martínez, Celestino; Chavarría, Carmen; Sharpe, Diana M. T.; De León, Luis Fernando

    2016-01-01

    Colour polymorphism is a recurrent feature of natural populations, and its maintenance has been studied in a range of taxa in their native ranges. However, less is known about whether (and how) colour polymorphism is maintained when populations are removed from their native environments, as in the case of introduced species. We here address this issue by analyzing variation in colour patterns in recently-discovered introduced populations of the guppy (Poecilia reticulata) in Panama. Specifically, we use classic colour analysis to estimate variation in the number and the relative area of different colour spots across low predation sites in the introduced Panamanian range of the species. We then compare this variation to that found in the native range of the species under low- and high predation regimes. We found aspects of the colour pattern that were both consistent and inconsistent with the classical paradigm of colour evolution in guppies. On one hand, the same colours that dominated in native populations (orange, iridescent and black) were also the most dominant in the introduced populations in Panama. On the other, there were no clear differences between either introduced-low and native low- and high predation populations. Our results are therefore only partially consistent with the traditional role of female preference in the absence of predators, and suggest that additional factors could influence colour patterns when populations are removed from their native environments. Future research on the interaction between female preference and environmental variability (e.g. multifarious selection), could help understand adaptive variation in this widely-introduced species, and the contexts under which variation in adaptive traits parallels (or not) variation in the native range. PMID:26863538

  4. Fortune favours the bold: a higher predator reduces the impact of a native but not an invasive intermediate predator.

    PubMed

    Barrios-O'Neill, Daniel; Dick, Jaimie T A; Emmerson, Mark C; Ricciardi, Anthony; MacIsaac, Hugh J; Alexander, Mhairi E; Bovy, Helene C

    2014-05-01

    Emergent multiple predator effects (MPEs) might radically alter predictions of predatory impact that are based solely on the impact of individuals. In the context of biological invasions, determining if and how the individual-level impacts of invasive predators relates to their impacts in multiple-individual situations will inform understanding of how such impacts might propagate through recipient communities. Here, we use functional responses (the relationship between prey consumption rate and prey density) to compare the impacts of the invasive freshwater mysid crustacean Hemimysis anomala with a native counterpart Mysis salemaai when feeding on basal cladoceran prey (i) as individuals, (ii) in conspecific groups and (iii) in conspecific groups in the presence of a higher fish predator, Gasterosteus aculeatus. In the absence of the higher predator, the invader consumed significantly more basal prey than the native, and consumption was additive for both mysid species - that is, group consumption was predictable from individual-level consumption. Invaders and natives were themselves equally susceptible to predation when feeding with the higher fish predator, but an MPE occurred only between the natives and higher predator, where consumption of basal prey was significantly reduced. In contrast, consumption by the invaders and higher predator remained additive. The presence of a higher predator serves to exacerbate the existing difference in individual-level consumption between invasive and native mysids. We attribute the mechanism responsible for the MPE associated with the native to a trait-mediated indirect interaction, and further suggest that the relative indifference to predator threat on the part of the invader contributes to its success and impacts within invaded communities. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.

  5. Two sides of a coin: Effects of climate change on the native and non-native distribution of Colossoma macropomum in South America

    PubMed Central

    Lopes, Taise M.; Bailly, Dayani; Almeida, Bia A.; Santos, Natália C. L.; Gimenez, Barbara C. G.; Landgraf, Guilherme O.; Sales, Paulo C. L.; Lima-Ribeiro, Matheus S.; Cassemiro, Fernanda A. S.; Rangel, Thiago F.; Diniz-Filho, José A. F.; Agostinho, Angelo A.; Gomes, Luiz C.

    2017-01-01

    Climate change and species invasions interact in nature, disrupting biological communities. Based on this knowledge, we simultaneously assessed the effects of climate change on the native distribution of the Amazonian fish Colossoma macropomum as well as on its invasiveness across river basins of South America, using ecological niche modeling. We used six niche models within the ensemble forecast context to predict the geographical distribution of C. macropomum for the present time, 2050 and 2080. Given that this species has been continuously introduced into non-native South American basins by fish farming activities, we added the locations of C. macropomum farms into the modeling process to obtain a more realistic scenario of its invasive potential. Based on modelling outputs we mapped climate refuge areas at different times. Our results showed that a plenty of climatically suitable areas for the occurrence of C. macropomum occurrence are located outside the original basins at the present time and that its invasive potential is greatly amplified by fish farms. Simulations of future geographic ranges revealed drastic range contraction in the native region, implying concerns not only with respect to the species conservation but also from a socio-economic perspective since the species is a cornerstone of artisanal and commercial fisheries in the Amazon. Although the invasive potential is projected to decrease in the face of climate change, climate refugia will concentrate in Paraná River, Southeast Atlantic and East Atlantic basins, putting intense, negative pressures on the native fish fauna these regions. Our findings show that short and long-term management actions are required for: i) the conservation of natural stocks of C. macropomum in the Amazon, and ii) protecting native fish fauna in the climate refuges of the invaded regions. PMID:28654663

  6. Low Predictability of Colour Polymorphism in Introduced Guppy (Poecilia reticulata) Populations in Panama.

    PubMed

    Martínez, Celestino; Chavarría, Carmen; Sharpe, Diana M T; De León, Luis Fernando

    2016-01-01

    Colour polymorphism is a recurrent feature of natural populations, and its maintenance has been studied in a range of taxa in their native ranges. However, less is known about whether (and how) colour polymorphism is maintained when populations are removed from their native environments, as in the case of introduced species. We here address this issue by analyzing variation in colour patterns in recently-discovered introduced populations of the guppy (Poecilia reticulata) in Panama. Specifically, we use classic colour analysis to estimate variation in the number and the relative area of different colour spots across low predation sites in the introduced Panamanian range of the species. We then compare this variation to that found in the native range of the species under low- and high predation regimes. We found aspects of the colour pattern that were both consistent and inconsistent with the classical paradigm of colour evolution in guppies. On one hand, the same colours that dominated in native populations (orange, iridescent and black) were also the most dominant in the introduced populations in Panama. On the other, there were no clear differences between either introduced-low and native low- and high predation populations. Our results are therefore only partially consistent with the traditional role of female preference in the absence of predators, and suggest that additional factors could influence colour patterns when populations are removed from their native environments. Future research on the interaction between female preference and environmental variability (e.g. multifarious selection), could help understand adaptive variation in this widely-introduced species, and the contexts under which variation in adaptive traits parallels (or not) variation in the native range.

  7. Synergistic impacts by an invasive amphipod and an invasive fish explain native gammarid extinction.

    PubMed

    Beggel, S; Brandner, J; Cerwenka, A F; Geist, J

    2016-07-14

    Worldwide freshwater ecosystems are increasingly affected by invasive alien species. In particular, Ponto-Caspian gobiid fishes and amphipods are suspected to have pronounced effects on aquatic food webs. However, there is a lack of systematic studies mechanistically testing the potential synergistic effects of invasive species on native fauna. In this study we investigated the interrelations between the invasive amphipod Dikerogammarus villosus and the invasive fish species Neogobius melanostomus in their effects on the native amphipod Gammarus pulex. We hypothesized selective predation by the fish as a driver for displacement of native species resulting in potential extinction of G. pulex. The survival of G. pulex in the presence of N. melanostomus in relation to the presence of D. villosus and availability of shelter was analyzed in the context of behavioural differences between the amphipod species. Gammarus pulex had a significantly higher susceptibility to predation by N. melanostomus compared to D. villosus in all experiments, suggesting preferential predation by this fish on native gammarids. Furthermore, the presence of D. villosus significantly increased the vulnerability of G. pulex to fish predation. Habitat structure was an important factor for swimming activity of amphipods and their mortality, resulting in a threefold decrease in amphipods consumed with shelter habitat structures provided. Behavioral differences in swimming activity were additionally responsible for higher predation rates on G. pulex. Intraguild predation could be neglected within short experimental durations. The results of this study provide evidence for synergistic effects of the two invasive Ponto-Caspian species on the native amphipod as an underlying process of species displacements during invasion processes. Prey behaviour and monotonous habitat structures additionally contribute to the decline of the native gammarid fauna in the upper Danube River and elsewhere.

  8. Comparison of phenolic compounds and the effects of invasive and native species in East Asia: Support for the novel weapons hypothesis

    USGS Publications Warehouse

    Kim, Y.-O.; Lee, E.J.

    2011-01-01

    One prediction of the novel weapons hypothesis (NWH) for the dominance of exotic invasive plant species is that the allelopathic effects of successful invaders will, in general, be more biochemically inhibitory to native species and microbes in invaded regions than the native plants themselves. However, no study has compared biochemical concentrations, compositions, or effects of large numbers of native species to those of large numbers of invasive species. In this context we tested the allelopathic and antimicrobial potentials of nine native plant species and nine invasive species in East Asia by comparing their broad phenolic contents and the effects of extracts made from each of the species on target plants and soil fungi. Three of the invasive species, including Eupatorium rugosum, had higher concentrations of total phenolic compounds than any of the native species, and the mean concentration of total phenolics for invasive species was 2.6 times greater than the mean for native species. Only scopoletin was novel to the invasive species, being found in all of nine invasive species, but not in the native species. More importantly, the effects of the total suites of phenolic compounds produced by invasive species differed from the effects of phenolics produced by natives. Extracts of invasive species reduced radicle growth of the three test plant species by 60-80%, but extracts of native species reduced radicle growth by only 30-50%. Extracts of invasive species reduced shoot growth of the three test species by 20-40%, but the overall effect of native species' extract was to stimulate shoot growth. The antimicrobial activity of invasive species was also significantly higher than that of native species. It should be noted that phenolics are just one component of a plant's potential allelopathic arsenal and non-phenolic compounds are likely to play a role in the total extract effect. For example, extracts of P. americana contained the lowest levels of phenolic compounds, but exhibited the strongest inhibition effect. We could not determine whether the greater inhibitory effects of the extracts from invasive species were due to novel combinations of chemicals or higher concentrations of chemicals, but our results are consistent with the predictions of the NWH. ?? 2010 The Ecological Society of Japan.

  9. The Native Production of the Sesquiterpene Isopterocarpolone by Streptomyces sp. RM-14-6

    PubMed Central

    Shaaban, Khaled A.; Singh, Shanteri; Elshahawi, Sherif I.; Wang, Xiachang; Ponomareva, Larissa V.; Sunkara, Manjula; Copley, Gregory C.; Hower, James C.; Morris, Andrew J.; Kharel, Madan K.; Thorson, Jon S.

    2013-01-01

    We report the production, isolation and structure elucidation of the sesquiterpene isopterocarpolone from an Appalachian isolate Streptomyces species RM-14-6. While isopterocarpolone was previously put forth as a putative plant metabolite, the current study highlights the first native bacterial production of isopterocarpolone and the first full characterization of isopterocarpolone using 1D and 2D NMR spectroscopy and HR-ESI mass spectrometry. Considering the biosynthesis of closely related metabolites (geosmin or 5-epiaristolochene), the structure of isopterocarpolone also suggests the potential participation of one or more unique enzymatic transformations. In this context, this work also sets the stage for the elucidation of potentially novel bacterial biosynthetic machinery. PMID:24237421

  10. Asian Indian views on diet and health in the United States: importance of understanding cultural and social factors to address disparities.

    PubMed

    Mukherjea, Arnab; Underwood, Kelsey Clark; Stewart, Anita L; Ivey, Susan L; Kanaya, Alka M

    2013-01-01

    This study describes Asian Indian immigrant perspectives surrounding dietary beliefs and practices to identify intervention targets for diabetes and heart disease prevention. Participants were asked about conceptualizations of relationships between culture, food, and health during 4 focus groups (n = 38). Findings reveal influences of beliefs from respondents' native India, preservation of cultural practices within the US social structure, conflicts with subsequent generations, and reinterpretation of health-related knowledge through a lens, hybridizing both "native" and "host" contexts. Galvanization of ethnically valued beliefs incorporating family and community structures is needed for multipronged approaches to reduce disproportionate burdens of disease among this understudied minority community.

  11. Millennial-scale sustainability of the Chesapeake Bay Native American oyster fishery

    PubMed Central

    Rick, Torben C.; Reeder-Myers, Leslie A.; Hofman, Courtney A.; Breitburg, Denise; Lockwood, Rowan; Henkes, Gregory; Kellogg, Lisa; Lowery, Darrin; Luckenbach, Mark W.; Mann, Roger; Ogburn, Matthew B.; Southworth, Melissa; Wah, John; Wesson, James; Hines, Anson H.

    2016-01-01

    Estuaries around the world are in a state of decline following decades or more of overfishing, pollution, and climate change. Oysters (Ostreidae), ecosystem engineers in many estuaries, influence water quality, construct habitat, and provide food for humans and wildlife. In North America’s Chesapeake Bay, once-thriving eastern oyster (Crassostrea virginica) populations have declined dramatically, making their restoration and conservation extremely challenging. Here we present data on oyster size and human harvest from Chesapeake Bay archaeological sites spanning ∼3,500 y of Native American, colonial, and historical occupation. We compare oysters from archaeological sites with Pleistocene oyster reefs that existed before human harvest, modern oyster reefs, and other records of human oyster harvest from around the world. Native American fisheries were focused on nearshore oysters and were likely harvested at a rate that was sustainable over centuries to millennia, despite changing Holocene climatic conditions and sea-level rise. These data document resilience in oyster populations under long-term Native American harvest, sea-level rise, and climate change; provide context for managing modern oyster fisheries in the Chesapeake Bay and elsewhere around the world; and demonstrate an interdisciplinary approach that can be applied broadly to other fisheries. PMID:27217572

  12. Millennial-scale sustainability of the Chesapeake Bay Native American oyster fishery.

    PubMed

    Rick, Torben C; Reeder-Myers, Leslie A; Hofman, Courtney A; Breitburg, Denise; Lockwood, Rowan; Henkes, Gregory; Kellogg, Lisa; Lowery, Darrin; Luckenbach, Mark W; Mann, Roger; Ogburn, Matthew B; Southworth, Melissa; Wah, John; Wesson, James; Hines, Anson H

    2016-06-07

    Estuaries around the world are in a state of decline following decades or more of overfishing, pollution, and climate change. Oysters (Ostreidae), ecosystem engineers in many estuaries, influence water quality, construct habitat, and provide food for humans and wildlife. In North America's Chesapeake Bay, once-thriving eastern oyster (Crassostrea virginica) populations have declined dramatically, making their restoration and conservation extremely challenging. Here we present data on oyster size and human harvest from Chesapeake Bay archaeological sites spanning ∼3,500 y of Native American, colonial, and historical occupation. We compare oysters from archaeological sites with Pleistocene oyster reefs that existed before human harvest, modern oyster reefs, and other records of human oyster harvest from around the world. Native American fisheries were focused on nearshore oysters and were likely harvested at a rate that was sustainable over centuries to millennia, despite changing Holocene climatic conditions and sea-level rise. These data document resilience in oyster populations under long-term Native American harvest, sea-level rise, and climate change; provide context for managing modern oyster fisheries in the Chesapeake Bay and elsewhere around the world; and demonstrate an interdisciplinary approach that can be applied broadly to other fisheries.

  13. Understanding students' epistemologies: Examining practice and meaning in community contexts

    NASA Astrophysics Data System (ADS)

    Bang, Megan Elisabeth

    There is a great need to raise the levels of science achievement for those groups of children who have traditionally underperformed. Prior cognitive research with Native people suggests that problems with achievement for Native students may be more complicated then simple problems with knowing or not knowing content knowledge. This dissertation hypothesizes that Native Americans engage in practices and have funds of knowledge that facilitate sophisticated reasoning in the domain of science. However, the knowledge and patterns of reasoning are not elicited, acceptable, or recognized in classroom science, or perhaps are in conflict with classroom science. Furthermore the divergence is not simply in the details of what is known; there is discord at the level of epistemology, in the fundamental ways in which Native people conceptualize knowledge of the natural world. This work proposes a new framework, Micro-practice epistemology, for understanding epistemology. I propose that epistemology should be understood as implicitly and explicitly imbedded in the worldviews, values, beliefs and practices of our everyday lives. Using both qualitative and quantitative methods this work investigates the everyday practices related to nature, the epistemological stances and biological knowledge embedded in those practices in a 3X3 model (age cohort: child, adult, elder X community). The three communities involved in this work include: Chicago urban Indian community, Menominee reservation community, and a rural working poor white community. I find significant differences in all three areas across communities. Native communities tend to participate in practices in which some aspect of nature is fore-grounded while non-Native participants tended to participate in practices in which nature is the back-grounded. These findings are extended to explore the ways in which worldviews and values are connected to practice and knowledge about the natural world. I find significant differences in worldviews and values between Native and non-Native communities. Finally this dissertation explores the Native children's perceptions of values and meaning between their science teachers and their community elders. I find Native children are acutely aware of significant differences in values and core understandings of biology between their science teachers and their elders. The epistemological implications of these differences are discussed.

  14. High Efficient Expression, Purification, and Functional Characterization of Native Human Epidermal Growth Factor in Escherichia coli.

    PubMed

    Ma, Yi; Yu, Jieying; Lin, Jinglian; Wu, Shaomin; Li, Shan; Wang, Jufang

    2016-01-01

    Human epidermal growth factor (hEGF) is a small, mitotic growth polypeptide that promotes the proliferation of various cells and is widely applied in clinical practices. However, high efficient expression of native hEGF in Escherichia coli has not been successful, since three disulfide bonds in monomer hEGF made it unable to fold into correct 3D structure using in vivo system. To tackle this problem, we fused Mxe GyrA intein (Mxe) at the C-terminal of hEGF followed by small ubiquitin-related modifier (SUMO) and 10x His-tag to construct a chimeric protein hEGF-Mxe-SUMO-H 10 . The fusion protein was highly expressed at the concentration of 281 mg/L and up to 59.5% of the total cellular soluble proteins. The fusion protein was purified by affinity chromatography and 29.4 mg/L of native hEGF can be released by thiol induced N-terminal cleavage without any proteases. The mitotic activity in Balb/c 3T3 cells is proliferated by commercial and recombinant hEGF measured with methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay which indicated that recombinant hEGF protein stimulates the cell proliferation similar to commercial protein. This study significantly improved the yield and reduced the cost of hEGF in the recombinant E. coli system and could be a better strategy to produce native hEGF for pharmaceutical development.

  15. In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

    PubMed

    Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

    2016-05-01

    High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining.

  16. The Social Costs of Academic Success across Ethnic Groups

    PubMed Central

    Fuller-Rowell, Thomas E.; Doan, Stacey N.

    2010-01-01

    This study explores the longitudinal association between academic achievement and social acceptance across ethnic groups in a nationally representative sample of adolescents (N = 13,570; Mage = 15.5 years). The effects of school context are also considered. Results show that African American and Native American adolescents experience greater social costs with academic success than Whites. Pertaining to school context, findings suggest that the differential social consequences of achievement experienced by African Americans are greatest in more highly achieving schools, but only when these schools have a smaller percentage of Black students. Students from Mexican decent also showed differential social costs with achievement in particular contexts. The implications of these findings to theory, policy, and future research are discussed. PMID:21077858

  17. Competition overwhelms the positive plant-soil feedback generated by an invasive plant.

    PubMed

    Crawford, Kerri M; Knight, Tiffany M

    2017-01-01

    Invasive plant species can modify soils in a way that benefits their fitness more than the fitness of native species. However, it is unclear how competition among plant species alters the strength and direction of plant-soil feedbacks. We tested how community context altered plant-soil feedback between the non-native invasive forb Lespedeza cuneata and nine co-occurring native prairie species. In a series of greenhouse experiments, we grew plants individually and in communities with soils that differed in soil origin (invaded or uninvaded by L. cuneata) and in soils that were live vs. sterilized. In the absence of competition, L. cuneata produced over 60% more biomass in invaded than uninvaded soils, while native species performance was unaffected. The absence of a soil origin effect in sterile soil suggests that the positive plant-soil feedback was caused by differences in the soil biota. However, in the presence of competition, the positive effect of soil origin on L. cuneata growth disappeared. These results suggest that L. cuneata may benefit from positive plant-soil feedback when establishing populations in disturbed landscapes with few interspecific competitors, but does not support the hypothesis that plant-soil feedbacks influence competitive outcomes between L. cuneata and native plant species. These results highlight the importance of considering whether competition influences the outcome of interactions between plants and soils.

  18. Factors associated with intensiveness of use of child preventive health services in Taiwan: a comparative study between cross-cultural immigrant families and native-born families.

    PubMed

    Chien, Su-Chen; Yeh, Yen-Po; Wu, Jyun-Yi; Lin, Chun-Hsiu; Chang, Pei-Chi; Fang, Chiung-Hui; Yang, Hao-Jan

    2013-01-01

    To compare intensiveness of use of child preventive health services (CPHS) between cross-cultural immigrant families and native-born families in Taiwan and to explore factors associated with differences in intensiveness of CPHS use. Cross-cultural immigrant families were defined as families where the mother was an immigrant from another southeast Asian country. In native-born families, both parents were Taiwanese-born. Data were collected from 318 immigrant mothers and 340 native-born mothers of children aged 7 years or younger in a cross-sectional survey in central Taiwan. A social determinants framework of health inequities was constructed, and ordinal logistic regression models were used to examine the effect of four domains of intermediary determinants on the relationship between family type and underuse of CPHS: CPHS-related factors, medical-related factors, maternal acculturation factors, and sociodemographic/socioeconomic characteristics. Cross-cultural immigrant families were less likely to intensively use CPHS than native-born families. This difference appeared to be mediated by the greater likelihood of having an older child or a lower educated father in cross-cultural families. Findings of this study highlight the importance of promoting health behaviors and combating health inequities and social inequalities for cross-cultural immigrant families in Taiwan from a sociodemographic/socioeconomic and political context.

  19. In search of cellular control: signal transduction in context

    NASA Technical Reports Server (NTRS)

    Ingber, D.

    1998-01-01

    The field of molecular cell biology has experienced enormous advances over the last century by reducing the complexity of living cells into simpler molecular components and binding interactions that are amenable to rigorous biochemical analysis. However, as our tools become more powerful, there is a tendency to define mechanisms by what we can measure. The field is currently dominated by efforts to identify the key molecules and sequences that mediate the function of critical receptors, signal transducers, and molecular switches. Unfortunately, these conventional experimental approaches ignore the importance of supramolecular control mechanisms that play a critical role in cellular regulation. Thus, the significance of individual molecular constituents cannot be fully understood when studied in isolation because their function may vary depending on their context within the structural complexity of the living cell. These higher-order regulatory mechanisms are based on the cell's use of a form of solid-state biochemistry in which molecular components that mediate biochemical processing and signal transduction are immobilized on insoluble cytoskeletal scaffolds in the cytoplasm and nucleus. Key to the understanding of this form of cellular regulation is the realization that chemistry is structure and hence, recognition of the the importance of architecture and mechanics for signal integration and biochemical control. Recent work that has unified chemical and mechanical signaling pathways provides a glimpse of how this form of higher-order cellular control may function and where paths may lie in the future.

  20. Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator and Drugs: Insights from Cellular Trafficking.

    PubMed

    Bridges, Robert J; Bradbury, Neil A

    2018-01-01

    The eukaryotic cell is organized into membrane-delineated compartments that are characterized by specific cadres of proteins sustaining biochemically distinct cellular processes. The appropriate subcellular localization of proteins is key to proper organelle function and provides a physiological context for cellular processes. Disruption of normal trafficking pathways for proteins is seen in several genetic diseases, where a protein's absence for a specific subcellular compartment leads to organelle disruption, and in the context of an individual, a disruption of normal physiology. Importantly, several drug therapies can also alter protein trafficking, causing unwanted side effects. Thus, a deeper understanding of trafficking pathways needs to be appreciated as novel therapeutic modalities are proposed. Despite the promising efficacy of novel therapeutic agents, the intracellular bioavailability of these compounds has proved to be a potential barrier, leading to failures in treatments for various diseases and disorders. While endocytosis of drug moieties provides an efficient means of getting material into cells, the subsequent release and endosomal escape of materials into the cytosol where they need to act has been a barrier. An understanding of cellular protein/lipid trafficking pathways has opened up strategies for increasing drug bioavailability. Approaches to enhance endosomal exit have greatly increased the cytosolic bioavailability of drugs and will provide a means of investigating previous drugs that may have been shelved due to their low cytosolic concentration.

  1. Early biocompatibility of crosslinked and non-crosslinked biologic meshes in a porcine model of ventral hernia repair.

    PubMed

    Melman, L; Jenkins, E D; Hamilton, N A; Bender, L C; Brodt, M D; Deeken, C R; Greco, S C; Frisella, M M; Matthews, B D

    2011-04-01

    Biologic meshes have unique physical properties as a result of manufacturing techniques such as decellularization, crosslinking, and sterilization. The purpose of this study is to directly compare the biocompatibility profiles of five different biologic meshes, AlloDerm(®) (non-crosslinked human dermal matrix), PeriGuard(®) (crosslinked bovine pericardium), Permacol(®) (crosslinked porcine dermal matrix), Strattice(®) (non-crosslinked porcine dermal matrix), and Veritas(®) (non-crosslinked bovine pericardium), using a porcine model of ventral hernia repair. Full-thickness fascial defects were created in 20 Yucatan minipigs and repaired with the retromuscular placement of biologic mesh 3 weeks later. Animals were euthanized at 1 month and the repair sites were subjected to tensile testing and histologic analysis. Samples of unimplanted (de novo) meshes and native porcine abdominal wall were also analyzed for their mechanical properties. There were no significant differences in the biomechanical characteristics between any of the mesh-repaired sites at 1 month postimplantation or between the native porcine abdominal wall without implanted mesh and the mesh-repaired sites (P > 0.05 for all comparisons). Histologically, non-crosslinked materials exhibited greater cellular infiltration, extracellular matrix (ECM) deposition, and neovascularization compared to crosslinked meshes. While crosslinking differentiates biologic meshes with regard to cellular infiltration, ECM deposition, scaffold degradation, and neovascularization, the integrity and strength of the repair site at 1 month is not significantly impacted by crosslinking or by the de novo strength/stiffness of the mesh.

  2. Sociopolitical context and depressive symptoms in an older Mexican-origin population

    NASA Astrophysics Data System (ADS)

    Miranda, Patricia Yvonne

    A large proportion of older adult Latinos have at least one chronic physical health condition; those same individuals who also exhibit depressive symptoms experience higher mortality rates. Given their projected population growth of 500% by 2050, it is important to disentangle the factors influencing the health status of Latinos aged 65 and older, specifically those who also experience depressive symptoms. Prior studies of depressive symptoms among Latino populations have often failed to consider the role of sociopolitical context---that is, the social, economic, political and historical circumstances that shape an individual's lived experience---and its contribution to understanding within-group differences for health outcomes. This study explores the relationships between sociopolitical context and number of depressive symptoms among an older Mexican-origin population in the U.S., and seeks to disentangle the importance of sociopolitical context from other widely used group stratifications for capturing U.S.-Mexican experiences, including nativity status, length of residence in the U.S., and place of residence during formative years. Study findings do not support rejecting the null hypothesis that there were differences in number of depressive symptoms by nativity status, length of residence in the U.S., or place of residence during formative years. Rather, findings suggest that the interaction of sociopolitical context and the age at which individuals arrive in the U.S. has a significant association with number of depressive symptoms among immigrants. This study takes a novel approach to examine the relationships between sociopolitical context at time of entry in the U.S. and symptoms of depression in later life. The implications of its findings for immigration as well as other social policies are discussed. The significant relationship between the interaction of sociopolitical context during time of entry into the U.S. and age of arrival into the U.S. suggests that contextual differences are related to a disparate number of depressive symptoms for this population. Thus, it is critical for researchers to understand contextual differences more broadly, and how past and future social policies influence health.

  3. Second Language Use Facilitates Implicit Emotion Regulation via Content Labeling

    PubMed Central

    Morawetz, Carmen; Oganian, Yulia; Schlickeiser, Ulrike; Jacobs, Arthur M.; Heekeren, Hauke R.

    2017-01-01

    Previous studies reported that negative stimuli induced less affect in bilinguals when stimuli were presented in bilinguals’ second, weaker language (L2) than when they were presented in their native language (L1). This effect of L2 use was attributed to increased emotional distance as well as to increased levels of cognitive control during L2 use. Here we investigated how explicit (cognitive reappraisal, i.e., reinterpreting the meaning of the emotional stimulus to alter its emotional impact) and implicit (content labeling, i.e., categorizing the content of the image; and emotion labeling, i.e., naming the emotion induced by the emotional stimulus) emotion regulation strategies are altered in an L2 (English) context in German native speakers with medium to high proficiency in their L2. While previous studies used linguistic stimuli, such as words, to induce affect, here we used images to test whether reduced affect could also be observed for non-linguistic stimuli when presented in an L2 context. We hypothesized that the previously implicated increase in emotional distance and cognitive control in an L2 would result in an L2 advantage in emotion regulation (i.e., leading to less negative emotions compared to an L1 context), by strengthening the effect of linguistic re-evaluation on the evoked emotions. Using a classic emotion regulation paradigm, we examined changes in subjective emotional state ratings during reappraisal, emotion labeling and content labeling in a L1 and L2 context. We found that the strength of evoked affective responses did not depend on the language context in which an image was presented. Crucially, content labeling in L2 was more effective than in L1, whereas emotion labeling did not differ between languages. Overall, evoked responses were regulated most effectively through explicit emotion regulation (reappraisal) in L1 and L2 context. These results demonstrate an L2 advantage effect for emotion regulation through content labeling and suggest that L2 context alters sub-processes implicated in content labeling but not emotion labeling. PMID:28360873

  4. Single-Cell and Single-Molecule Analysis of Gene Expression Regulation.

    PubMed

    Vera, Maria; Biswas, Jeetayu; Senecal, Adrien; Singer, Robert H; Park, Hye Yoon

    2016-11-23

    Recent advancements in single-cell and single-molecule imaging technologies have resolved biological processes in time and space that are fundamental to understanding the regulation of gene expression. Observations of single-molecule events in their cellular context have revealed highly dynamic aspects of transcriptional and post-transcriptional control in eukaryotic cells. This approach can relate transcription with mRNA abundance and lifetimes. Another key aspect of single-cell analysis is the cell-to-cell variability among populations of cells. Definition of heterogeneity has revealed stochastic processes, determined characteristics of under-represented cell types or transitional states, and integrated cellular behaviors in the context of multicellular organisms. In this review, we discuss novel aspects of gene expression of eukaryotic cells and multicellular organisms revealed by the latest advances in single-cell and single-molecule imaging technology.

  5. Assessment of elder mistreatment in two American Indian samples: psychometric characteristics of the HS-EAST and the Native Elder Life-Financial Exploitation and -Neglect measures.

    PubMed

    Jervis, Lori L; Fickenscher, Alexandra; Beals, Janette

    2014-04-01

    Although elder mistreatment among ethnic minorities is increasingly gaining attention, our empirical knowledge of this phenomenon among American Indians remains quite limited, especially with respect to measurement. The Shielding American Indian Elders (SAIE) Project used a collaborative approach to explore culturally informed measurement of elder mistreatment in two American Indian elder samples (a Northern Plains reservation and a South Central metropolitan area). The project sought to investigate the performance characteristics of the commonly used Hwalek-Sengstock Elder Abuse Screening Test (HS-EAST), as well as to examine the psychometric properties of a new measure developed to capture culturally salient aspects of mistreatment in American Indian contexts--the Native Elder Life Scale (NELS). Using methods and samples comparable to those in the literature, the HS-EAST performed adequately in these Native samples. The NELS also shows promise for use with this population and assesses different aspects of elder mistreatment than does the HS-EAST.

  6. Early Cognitive Skills of Mexican-Origin Children: The Roles of Parental Nativity and Legal Status

    PubMed Central

    Landale, Nancy S.; Oropesa, R.S.; Noah, Aggie J.; Hillemeier, Marianne M.

    2016-01-01

    Although one-third of children of immigrants have undocumented parents, little is known about their early development. Using data from the Los Angeles Family and Neighborhood Survey and decennial census, we assessed how children’s cognitive skills at ages 3 to 5 vary by ethnicity, maternal nativity, and maternal legal status. Specifically, Mexican children of undocumented mothers were contrasted with Mexican children of documented mothers and Mexican, white, and black children with U.S.-born mothers. Mexican children of undocumented mothers had lower emergent reading skills than all other groups and lower emergent mathematics skills than all groups with U.S.-born mothers. Multilevel regression models showed that differences in reading skills are explained by aspects of the home environment, but the neighborhood context also matters. Cross-level interactions suggest that immigrant concentration boosts emergent reading and mathematics skills for children with undocumented parents, but does not similarly benefit children whose parents are native born. PMID:27194660

  7. Bridges to nowhere: hosts, migrants, and the chimera of social capital in three African cities.

    PubMed

    Madhavan, Sangeetha; Landau, Loren B

    2011-01-01

    Interest in migrant social networks and social capital has grown substantially over the past several decades. The relationship between “host” and “migrant” communities remains central to these scholarly debates. Recently urbanized cities in Africa, which include large numbers of “native-born” or internal migrants, challenge basic presumptions about host/migrant distinctions informing many of these discussions. Using comparable survey data from Johannesburg, Maputo, and Nairobi, we examine 1) the nature of social connectedness in terms of residence and nativity characteristics; and 2) the relationship between residence and nativity characteristics and three measures of trust within and across communities. Our findings suggest that the host/migrant distinction may not be particularly revealing in African cities where domestic mobility, social fragmentation and the absence of bridging institutions result in relatively low levels of trust both within and across communities. These findings underscore the need for new concepts to study “communities of strangers” and how people strategize their social mobility in urban contexts.

  8. Genetically Encoded Chemical Probes In Cells Reveal the Binding Path of Urocortin-I to CRF Class B GPCR

    PubMed Central

    Coin, Irene; Katritch, Vsevolod; Sun, Tingting; Xiang, Zheng; Siu, Fai Yiu; Beyermann, Michael; Stevens, Raymond C.; Wang, Lei

    2014-01-01

    SUMMARY Molecular determinants regulating the activation of class B G-protein coupled receptors (GPCRs) by native peptide agonists are largely unknown. We have investigated here the interaction between the corticotropin releasing factor receptor type 1 (CRF1R) and its native 40-mer peptide ligand Urocortin-I directly in mammalian cells. By incorporating unnatural amino acid photo-chemical and new click-chemical probes into the receptor, 44 inter-molecular spatial constraints have been derived for the ligand-receptor interaction. The data were analyzed in the context of the recently resolved crystal structure of CRF1R transmembrane domain and existing extracellular domain structures, yielding a complete conformational model for the peptide-receptor complex. Structural features of the receptor-ligand complex yield molecular insights on the mechanism of receptor activation. The experimental strategy provides unique information on full-length post-translationally modified GPCRs in the native membrane of the live cell, complementing in vitro biophysical reductionist approaches. PMID:24290358

  9. Crossing Boundaries: Nativity, Ethnicity, and Mate Selection

    PubMed Central

    Qian, Zhenchao; Glick, Jennifer E.; Baston, Christie

    2016-01-01

    The influx of immigrants has increased diversity among ethnic minorities and indicates that they may take multiple integration paths in American society. Previous research on ethnic integration often focuses on panethnic differences and few have explored ethnic diversity within a racial or panethnic context. Using 2000 U.S. census data for Puerto Rican, Mexican, Chinese, and Filipino origin individuals, we examine differences in marriage and cohabitation with whites, with other minorities, within a panethnic group, and within an ethnic group by nativity status. Ethnic endogamy is strong and, to a less extent, so is panethnic endogamy. Yet, marital or cohabiting unions with whites remain an important path of integration but differ significantly by ethnicity, nativity, age at arrival, and educational attainment. Meanwhile, ethnic differences in marriage and cohabitation with other racial or ethnic minorities are strong. Our analysis supports that unions with whites remain a major path of integration, but other paths of integration also become viable options for all ethnic groups. PMID:22350840

  10. Feeding status and basking requirements of freshwater turtles in an invasion context.

    PubMed

    Polo-Cavia, Nuria; López, Pilar; Martín, José

    2012-03-20

    Thermoregulatory behavior and feeding status are strongly related in ectotherms. A trade-off between maintenance of energy balance and digestion efficiency has been recently proposed to affect thermoregulation in these animals. On the other hand, competition for basking sites has been described between Iberian turtles and the introduced red-eared slider (Trachemys scripta elegans). T. scripta negatively interferes with basking behavior of native turtles and benefits from a greater capacity to retain body heat, which may likely result in thermoregulatory advantages for the introduced sliders. Consequently, complex effects and alterations in metabolic rates of native turtles might derive from a deficient basking behavior. We compared the basking requirements of the endangered native Spanish terrapin (Mauremys leprosa) and those of the introduced red-eared slider, analyzing the upper set point temperature (USP) (defined as the body temperature at which basking ceased) of both native and introduced turtles, under feeding and fasting conditions. We found higher values of USP in the native species, and a reduction of this temperature associated with food deprivation in the two turtle species. This adjustment of thermoregulatory behavior to the nutritional status found in freshwater turtles suggests that ectotherms benefit from metabolic depression as an adaptive mechanism to preserve energy during periods of fasting. However, a reduction in metabolic rates induced by competition with sliders might lead M. leprosa to a prolonged deficiency of their physiological functions, thus incurring increased predation risk and health costs, and ultimately favoring the recession of this native species in Mediterranean habitats. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Evaluating the lexico-grammatical differences in the writing of native and non-native speakers of English in peer-reviewed medical journals in the field of pediatric oncology: Creation of the genuine index scoring system

    PubMed Central

    Gayle, Alberto Alexander; Shimaoka, Motomu

    2017-01-01

    Introduction The predominance of English in scientific research has created hurdles for “non-native speakers” of English. Here we present a novel application of native language identification (NLI) for the assessment of medical-scientific writing. For this purpose, we created a novel classification system whereby scoring would be based solely on text features found to be distinctive among native English speakers (NS) within a given context. We dubbed this the “Genuine Index” (GI). Methodology This methodology was validated using a small set of journals in the field of pediatric oncology. Our dataset consisted of 5,907 abstracts, representing work from 77 countries. A support vector machine (SVM) was used to generate our model and for scoring. Results Accuracy, precision, and recall of the classification model were 93.3%, 93.7%, and 99.4%, respectively. Class specific F-scores were 96.5% for NS and 39.8% for our benchmark class, Japan. Overall kappa was calculated to be 37.2%. We found significant differences between countries with respect to the GI score. Significant correlation was found between GI scores and two validated objective measures of writing proficiency and readability. Two sets of key terms and phrases differentiating NS and non-native writing were identified. Conclusions Our GI model was able to detect, with a high degree of reliability, subtle differences between the terms and phrasing used by native and non-native speakers in peer reviewed journals, in the field of pediatric oncology. In addition, L1 language transfer was found to be very likely to survive revision, especially in non-Western countries such as Japan. These findings show that even when the language used is technically correct, there may still be some phrasing or usage that impact quality. PMID:28212419

  12. Evaluating the lexico-grammatical differences in the writing of native and non-native speakers of English in peer-reviewed medical journals in the field of pediatric oncology: Creation of the genuine index scoring system.

    PubMed

    Gayle, Alberto Alexander; Shimaoka, Motomu

    2017-01-01

    The predominance of English in scientific research has created hurdles for "non-native speakers" of English. Here we present a novel application of native language identification (NLI) for the assessment of medical-scientific writing. For this purpose, we created a novel classification system whereby scoring would be based solely on text features found to be distinctive among native English speakers (NS) within a given context. We dubbed this the "Genuine Index" (GI). This methodology was validated using a small set of journals in the field of pediatric oncology. Our dataset consisted of 5,907 abstracts, representing work from 77 countries. A support vector machine (SVM) was used to generate our model and for scoring. Accuracy, precision, and recall of the classification model were 93.3%, 93.7%, and 99.4%, respectively. Class specific F-scores were 96.5% for NS and 39.8% for our benchmark class, Japan. Overall kappa was calculated to be 37.2%. We found significant differences between countries with respect to the GI score. Significant correlation was found between GI scores and two validated objective measures of writing proficiency and readability. Two sets of key terms and phrases differentiating NS and non-native writing were identified. Our GI model was able to detect, with a high degree of reliability, subtle differences between the terms and phrasing used by native and non-native speakers in peer reviewed journals, in the field of pediatric oncology. In addition, L1 language transfer was found to be very likely to survive revision, especially in non-Western countries such as Japan. These findings show that even when the language used is technically correct, there may still be some phrasing or usage that impact quality.

  13. Acute neuroinflammation impairs context discrimination memory and disrupts pattern separation processes in hippocampus.

    PubMed

    Czerniawski, Jennifer; Guzowski, John F

    2014-09-10

    Although it is known that immune system activation can impair cognition, no study to date has linked cognitive deficits during acute neuroinflammation to dysregulation of task-relevant neuronal ensemble activity. Here, we assessed both neural circuit activity and context discrimination memory retrieval, in a within-subjects design, of male rats given systemic administration of saline or lipopolysaccharide (LPS). Rats were exposed over several days to two similar contexts: one of which was paired with weak foot shock and the other was not. After reaching criteria for discriminative freezing, rats were given systemic LPS or saline injection and tested for retrieval of context discrimination 6 h later. Importantly, LPS administration produced an acute neuroinflammatory response in dorsal hippocampus at this time (as assessed by elevation of proinflammatory cytokine mRNA levels) and abolished retrieval of the previously acquired discrimination. The impact of neuroinflammation on hippocampal CA3 and CA1 neural circuit activity was assessed using the Arc/Homer1a cellular analysis of temporal activity by fluorescence in situ hybridization imaging method. Whereas the saline-treated subjects discriminated and had low overlap of hippocampal ensembles activated in the two contexts, LPS-treated subjects did not discriminate and had greater ensemble overlap (i.e., reduced orthogonalization). Additionally, retrieval of standard contextual fear conditioning, which does not require context discrimination, was not affected by pretesting LPS administration. Together, the behavioral and circuit analyses data provide compelling evidence that LPS administration impairs context discrimination memory by disrupting cellular pattern separation processes within the hippocampus, thus linking acute neuroinflammation to disruption of specific neural circuit functions and cognitive impairment. Copyright © 2014 the authors 0270-6474/14/3412470-11$15.00/0.

  14. Acute Neuroinflammation Impairs Context Discrimination Memory and Disrupts Pattern Separation Processes in Hippocampus

    PubMed Central

    Czerniawski, Jennifer

    2014-01-01

    Although it is known that immune system activation can impair cognition, no study to date has linked cognitive deficits during acute neuroinflammation to dysregulation of task-relevant neuronal ensemble activity. Here, we assessed both neural circuit activity and context discrimination memory retrieval, in a within-subjects design, of male rats given systemic administration of saline or lipopolysaccharide (LPS). Rats were exposed over several days to two similar contexts: one of which was paired with weak foot shock and the other was not. After reaching criteria for discriminative freezing, rats were given systemic LPS or saline injection and tested for retrieval of context discrimination 6 h later. Importantly, LPS administration produced an acute neuroinflammatory response in dorsal hippocampus at this time (as assessed by elevation of proinflammatory cytokine mRNA levels) and abolished retrieval of the previously acquired discrimination. The impact of neuroinflammation on hippocampal CA3 and CA1 neural circuit activity was assessed using the Arc/Homer1a cellular analysis of temporal activity by fluorescence in situ hybridization imaging method. Whereas the saline-treated subjects discriminated and had low overlap of hippocampal ensembles activated in the two contexts, LPS-treated subjects did not discriminate and had greater ensemble overlap (i.e., reduced orthogonalization). Additionally, retrieval of standard contextual fear conditioning, which does not require context discrimination, was not affected by pretesting LPS administration. Together, the behavioral and circuit analyses data provide compelling evidence that LPS administration impairs context discrimination memory by disrupting cellular pattern separation processes within the hippocampus, thus linking acute neuroinflammation to disruption of specific neural circuit functions and cognitive impairment. PMID:25209285

  15. Symbiosis in the Context of an Invasive, Non-Native Grass: Fungal Biodiversity and Student Engagement

    NASA Astrophysics Data System (ADS)

    Lehr, Gavin

    Grasslands in the western United States face severe environmental threats including those brought about by climate change, such as changes in precipitation regimes and altered fire cycles; land-use conversion and development; and the introduction, establishment, and spread of non-native species. Lehmann's lovegrass (Eragrostis lehmanniana) was introduced to the southwestern United States in the early 1900s. Since its introduction, it has become the dominant grass in the mid-elevation grasslands of southern Arizona, including the Santa Rita Experimental Range (SRER), where it has displaced native grasses including Arizona cottontop, three awns, and gramas. Like all plants in terrestrial ecosystems, this grass harbors fungal symbionts that can be important for its establishment and persistence. This thesis focuses on fungal symbionts of Lehmann's lovegrass and has two components. First, the diversity and distributions of endophytes in Lehmann's lovegrass are evaluated in the context of biotic and abiotic factors in the SRER. Culturing from roots and shoots of Lehmann's lovegrass at points beneath and outside the canopy of native mesquites, which are encroaching on grasslands over time, provides insight into how a single plant species can exhibit local variation in the composition of its symbionts. Second, the thesis is used as the basis for engagement of students in science, technology, engineering, and mathematics (STEM) through the development and implementation of classroom- and field activities centered on endophytes, which help high school students address core learning aims while also gaining real research experience. Engaging students in important questions relevant to their local environment can catalyze interest in science and help students cross the threshold into research. The contributions of such approaches with respect to learning not only fulfills key next-generation science standards and common core objectives, but provides students with a meaningful introduction to the excitement, importance, and accessibility of science.

  16. Neighborhood context and immigrant children's physical activity.

    PubMed

    Brewer, Mackenzie; Kimbro, Rachel Tolbert

    2014-09-01

    Physical activity is an important determinant of obesity and overall health for children, but significant race/ethnic and nativity disparities exist in the amount of physical activity that children receive, with immigrant children particularly at risk for low levels of physical activity. In this paper, we examine and compare patterns in physical activity levels for young children of U.S.-born and immigrant mothers from seven race/ethnic and nativity groups, and test whether physical activity is associated with subjective (parent-reported) and objective (U.S. Census) neighborhood measures. The neighborhood measures include parental-reported perceptions of safety and physical and social disorder and objectively defined neighborhood socioeconomic disadvantage and immigrant concentration. Using restricted, geo-coded Early Childhood Longitudinal Study-Kindergarten (ECLS-K) data (N = 17,510) from 1998 to 1999 linked with U.S. Census 2000 data for the children's neighborhoods, we utilize zero-inflated Poisson (ZIP) models to predict the odds of physical inactivity and expected days of physical activity for kindergarten-aged children. Across both outcomes, foreign-born children have lower levels of physical activity compared to U.S.-born white children. This disparity is not attenuated by a child's socioeconomic, family, or neighborhood characteristics. Physical and social disorder is associated with higher odds of physical inactivity, while perceptions of neighborhood safety are associated with increased expected days of physical activity, but not with inactivity. Immigrant concentration is negatively associated with both physical activity outcomes, but its impact on the probability of physical inactivity differs by the child's race/ethnic and nativity group, such that it is particularly detrimental for U.S.-born white children's physical activity. Research interested in improving the physical activity patterns of minority and second-generation immigrant children should consider how neighborhood context differentially impacts the health and physical activity of children from various racial, ethnic and nativity backgrounds. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Language-Dependent Pitch Encoding Advantage in the Brainstem Is Not Limited to Acceleration Rates that Occur in Natural Speech

    ERIC Educational Resources Information Center

    Krishnan, Ananthanarayan; Gandour, Jackson T.; Smalt, Christopher J.; Bidelman, Gavin M.

    2010-01-01

    Experience-dependent enhancement of neural encoding of pitch in the auditory brainstem has been observed for only specific portions of native pitch contours exhibiting high rates of pitch acceleration, irrespective of speech or nonspeech contexts. This experiment allows us to determine whether this language-dependent advantage transfers to…

  18. Tribally Controlled Colleges: Making Good Medicine. American Indian Studies, Volume 3.

    ERIC Educational Resources Information Center

    Stein, Wayne J.

    This book traces the development of tribally controlled colleges (TCC), placing them in a historical context within Native American higher education and within the junior and community college movement. It examines the first 10 years of the movement, focusing in particular on six TCC's and the American Indian Higher Education Consortium (AIHEC),…

  19. Development and Use of an EFL Reading Practice Application for an Android Tablet Computer

    ERIC Educational Resources Information Center

    Ishikawa, Yasushige; Smith, Craig; Kondo, Mutsumi; Akano, Ichiro; Maher, Kate; Wada, Norihisa

    2014-01-01

    This paper reports on the use of an English-language reading practice application for an Android tablet computer with students who are not native speakers of English. The application materials for vocabulary learning in reading-passage contexts were created to include words from a database of low-frequency and technical noun-verb collocations…

  20. Is All Classroom Conduct Equal?: Teacher Contact with Parents of Racial/Ethnic Minority and Immigrant Adolescents

    ERIC Educational Resources Information Center

    Cherng, Hua-Yu Sebastian

    2016-01-01

    Background/Context: Parental involvement is a key ingredient in the educational success of students and an integral component of involvement is teacher-parent communication. One body of research finds that minority immigrant parents face barriers in interacting with schools, and communicate less with schools than native-born White parents.…

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