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Sample records for identify functional regions

  1. Using Spatial Semantics and Interactions to Identify Urban Functional Regions

    Directory of Open Access Journals (Sweden)

    Yandong Wang

    2018-03-01

    Full Text Available The spatial structures of cities have changed dramatically with rapid socio-economic development in ways that are not well understood. To support urban structural analysis and rational planning, we propose a framework to identify urban functional regions and quantitatively explore the intensity of the interactions between them, thus increasing the understanding of urban structures. A method for the identification of functional regions via spatial semantics is proposed, which involves two steps: (1 the study area is classified into three types of functional regions using taxi origin/destination (O/D flows; and (2 the spatial semantics for the three types of functional regions are demonstrated based on point-of-interest (POI categories. To validate the existence of urban functional regions, we explored the intensity of interactions quantitatively between them. A case study using POI data and taxi trajectory data from Beijing validates the proposed framework. The results show that the proposed framework can be used to identify urban functional regions and promotes an enhanced understanding of urban structures.

  2. A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.

    Science.gov (United States)

    Rand, Kristin A; Song, Chi; Dean, Eric; Serie, Daniel J; Curtin, Karen; Sheng, Xin; Hu, Donglei; Huff, Carol Ann; Bernal-Mizrachi, Leon; Tomasson, Michael H; Ailawadhi, Sikander; Singhal, Seema; Pawlish, Karen; Peters, Edward S; Bock, Cathryn H; Stram, Alex; Van Den Berg, David J; Edlund, Christopher K; Conti, David V; Zimmerman, Todd; Hwang, Amie E; Huntsman, Scott; Graff, John; Nooka, Ajay; Kong, Yinfei; Pregja, Silvana L; Berndt, Sonja I; Blot, William J; Carpten, John; Casey, Graham; Chu, Lisa; Diver, W Ryan; Stevens, Victoria L; Lieber, Michael R; Goodman, Phyllis J; Hennis, Anselm J M; Hsing, Ann W; Mehta, Jayesh; Kittles, Rick A; Kolb, Suzanne; Klein, Eric A; Leske, Cristina; Murphy, Adam B; Nemesure, Barbara; Neslund-Dudas, Christine; Strom, Sara S; Vij, Ravi; Rybicki, Benjamin A; Stanford, Janet L; Signorello, Lisa B; Witte, John S; Ambrosone, Christine B; Bhatti, Parveen; John, Esther M; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah J; Bandera, Elisa V; Birmann, Brenda M; Ingles, Sue A; Press, Michael F; Atanackovic, Djordje; Glenn, Martha J; Cannon-Albright, Lisa A; Jones, Brandt; Tricot, Guido; Martin, Thomas G; Kumar, Shaji K; Wolf, Jeffrey L; Deming Halverson, Sandra L; Rothman, Nathaniel; Brooks-Wilson, Angela R; Rajkumar, S Vincent; Kolonel, Laurence N; Chanock, Stephen J; Slager, Susan L; Severson, Richard K; Janakiraman, Nalini; Terebelo, Howard R; Brown, Elizabeth E; De Roos, Anneclaire J; Mohrbacher, Ann F; Colditz, Graham A; Giles, Graham G; Spinelli, John J; Chiu, Brian C; Munshi, Nikhil C; Anderson, Kenneth C; Levy, Joan; Zonder, Jeffrey A; Orlowski, Robert Z; Lonial, Sagar; Camp, Nicola J; Vachon, Celine M; Ziv, Elad; Stram, Daniel O; Hazelett, Dennis J; Haiman, Christopher A; Cozen, Wendy

    2016-12-01

    Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma. We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4 Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 × 10 -7 ) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7 CONCLUSIONS: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. ©2016 AACR. ©2016 American Association for Cancer Research.

  3. Identifying Dialect Regions from Syntactic Data

    NARCIS (Netherlands)

    Tjong Kim Sang, E.; Wieling, Martijn; Kroon, Martin; van Noord, Gertjan; Bouma, Gosse

    2017-01-01

    The Syntactic Atlas of Dutch Dialects (SAND) is a database of syntactic features observed in the language spoken by people from different dialect regions in The Netherlands and Flanders. We would like to know how specific syntactic features are for the different dialects. For this purpose we try to

  4. Identifying the source region of plasmaspheric hiss

    Czech Academy of Sciences Publication Activity Database

    Laakso, H.; Santolík, Ondřej; Horne, R.; Kolmašová, Ivana; Escoubet, P.; Masson, A.; Taylor, P.

    2015-01-01

    Roč. 42, č. 9 (2015), s. 3141-3149 ISSN 0094-8276 R&D Projects: GA MŠk LH12231 Institutional support: RVO:68378289 Keywords : plasmaspheric hiss * plasmaspheric drainage plumes * plasmasphere * equatorial region of plumes Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 4.212, year: 2015 http://onlinelibrary.wiley.com/doi/10.1002/2015GL063755/full

  5. Identifying Floppy and Rigid Regions in Proteins

    Science.gov (United States)

    Jacobs, D. J.; Thorpe, M. F.; Kuhn, L. A.

    1998-03-01

    In proteins it is possible to separate hard covalent forces involving bond lengths and bond angles from other weak forces. We model the microstructure of the protein as a generic bar-joint truss framework, where the hard covalent forces and strong hydrogen bonds are regarded as rigid bar constraints. We study the mechanical stability of proteins using FIRST (Floppy Inclusions and Rigid Substructure Topography) based on a recently developed combinatorial constraint counting algorithm (the 3D Pebble Game), which is a generalization of the 2D pebble game (D. J. Jacobs and M. F. Thorpe, ``Generic Rigidity: The Pebble Game'', Phys. Rev. Lett.) 75, 4051-4054 (1995) for the special class of bond-bending networks (D. J. Jacobs, "Generic Rigidity in Three Dimensional Bond-bending Networks", Preprint Aug (1997)). This approach is useful in identifying rigid motifs and flexible linkages in proteins, and thereby determines the essential degrees of freedom. We will show some preliminary results from the FIRST analysis on the myohemerythrin and lyozyme proteins.

  6. Which functional unit to identify sustainable foods?

    Science.gov (United States)

    Masset, Gabriel; Vieux, Florent; Darmon, Nicole

    2015-09-01

    In life-cycle assessment, the functional unit defines the unit for calculation of environmental indicators. The objective of the present study was to assess the influence of two functional units, 100 g and 100 kcal (420 kJ), on the associations between three dimensions for identifying sustainable foods, namely environmental impact (via greenhouse gas emissions (GHGE)), nutritional quality (using two distinct nutrient profiling systems) and price. GHGE and price data were collected for individual foods, and were each expressed per 100 g and per 100 kcal. Two nutrient profiling models, SAIN,LIM and UK Ofcom, were used to assess foods' nutritional quality. Spearman correlations were used to assess associations between variables. Sustainable foods were identified as those having more favourable values for all three dimensions. The French Individual and National Dietary Survey (INCA2), 2006-2007. Three hundred and seventy-three foods highly consumed in INCA2, covering 65 % of total energy intake of adult participants. When GHGE and price were expressed per 100 g, low-GHGE foods had a lower price and higher SAIN,LIM and Ofcom scores (r=0·59, -0·34 and -0·43, respectively), suggesting a compatibility between the three dimensions; 101 and 100 sustainable foods were identified with SAIN,LIM and Ofcom, respectively. When GHGE and price were expressed per 100 kcal, low-GHGE foods had a lower price but also lower SAIN,LIM and Ofcom scores (r=0·67, 0·51 and 0·47, respectively), suggesting that more environment-friendly foods were less expensive but also less healthy; thirty-four sustainable foods were identified with both SAIN,LIM and Ofcom. The choice of functional unit strongly influenced the compatibility between the sustainability dimensions and the identification of sustainable foods.

  7. Simple Model for Identifying Critical Regions in Atrial Fibrillation

    Science.gov (United States)

    Christensen, Kim; Manani, Kishan A.; Peters, Nicholas S.

    2015-01-01

    Atrial fibrillation (AF) is the most common abnormal heart rhythm and the single biggest cause of stroke. Ablation, destroying regions of the atria, is applied largely empirically and can be curative but with a disappointing clinical success rate. We design a simple model of activation wave front propagation on an anisotropic structure mimicking the branching network of heart muscle cells. This integration of phenomenological dynamics and pertinent structure shows how AF emerges spontaneously when the transverse cell-to-cell coupling decreases, as occurs with age, beyond a threshold value. We identify critical regions responsible for the initiation and maintenance of AF, the ablation of which terminates AF. The simplicity of the model allows us to calculate analytically the risk of arrhythmia and express the threshold value of transversal cell-to-cell coupling as a function of the model parameters. This threshold value decreases with increasing refractory period by reducing the number of critical regions which can initiate and sustain microreentrant circuits. These biologically testable predictions might inform ablation therapies and arrhythmic risk assessment.

  8. 40 CFR 255.10 - Criteria for identifying regions.

    Science.gov (United States)

    2010-07-01

    ... institutional gaps or inadequacies are found, regions should be identified keeping in mind which agencies would... section 208 of the Federal Water Pollution Control Act, with underground injection control agencies...

  9. SitesIdentify: a protein functional site prediction tool

    Directory of Open Access Journals (Sweden)

    Doig Andrew J

    2009-11-01

    Full Text Available Abstract Background The rate of protein structures being deposited in the Protein Data Bank surpasses the capacity to experimentally characterise them and therefore computational methods to analyse these structures have become increasingly important. Identifying the region of the protein most likely to be involved in function is useful in order to gain information about its potential role. There are many available approaches to predict functional site, but many are not made available via a publicly-accessible application. Results Here we present a functional site prediction tool (SitesIdentify, based on combining sequence conservation information with geometry-based cleft identification, that is freely available via a web-server. We have shown that SitesIdentify compares favourably to other functional site prediction tools in a comparison of seven methods on a non-redundant set of 237 enzymes with annotated active sites. Conclusion SitesIdentify is able to produce comparable accuracy in predicting functional sites to its closest available counterpart, but in addition achieves improved accuracy for proteins with few characterised homologues. SitesIdentify is available via a webserver at http://www.manchester.ac.uk/bioinformatics/sitesidentify/

  10. Genomic Regions Affecting Cheese Making Properties Identified in Danish Holsteins

    DEFF Research Database (Denmark)

    Gregersen, Vivi Raundahl; Bertelsen, Henriette Pasgaard; Poulsen, Nina Aagaard

    The cheese renneting process is affected by a number of factors associated to milk composition and a number of Danish Holsteins has previously been identified to have poor milk coagulation ability. Therefore, the aim of this study was to identify genomic regions affecting the technological...

  11. Coastal upwelling ecosystems are often identified as regions ...

    African Journals Online (AJOL)

    spamer

    ... are often identified as regions susceptible to seasonal blooms of harmful ... that the bay acts as a net importer of bottom water and net exporter of surface waters over a synoptic cycle. This ... waves or wind stress on the surface friction layer.

  12. Identifying functional thermodynamics in autonomous Maxwellian ratchets

    Science.gov (United States)

    Boyd, Alexander B.; Mandal, Dibyendu; Crutchfield, James P.

    2016-02-01

    We introduce a family of Maxwellian Demons for which correlations among information bearing degrees of freedom can be calculated exactly and in compact analytical form. This allows one to precisely determine Demon functional thermodynamic operating regimes, when previous methods either misclassify or simply fail due to approximations they invoke. This reveals that these Demons are more functional than previous candidates. They too behave either as engines, lifting a mass against gravity by extracting energy from a single heat reservoir, or as Landauer erasers, consuming external work to remove information from a sequence of binary symbols by decreasing their individual uncertainty. Going beyond these, our Demon exhibits a new functionality that erases bits not by simply decreasing individual-symbol uncertainty, but by increasing inter-bit correlations (that is, by adding temporal order) while increasing single-symbol uncertainty. In all cases, but especially in the new erasure regime, exactly accounting for informational correlations leads to tight bounds on Demon performance, expressed as a refined Second Law of thermodynamics that relies on the Kolmogorov-Sinai entropy for dynamical processes and not on changes purely in system configurational entropy, as previously employed. We rigorously derive the refined Second Law under minimal assumptions and so it applies quite broadly—for Demons with and without memory and input sequences that are correlated or not. We note that general Maxwellian Demons readily violate previously proposed, alternative such bounds, while the current bound still holds. As such, it broadly describes the minimal energetic cost of any computation by a thermodynamic system.

  13. Heat Roadmap Europe: Identifying strategic heat synergy regions

    International Nuclear Information System (INIS)

    Persson, U.; Möller, B.; Werner, S.

    2014-01-01

    This study presents a methodology to assess annual excess heat volumes from fuel combustion activities in energy and industry sector facilities based on carbon dioxide emission data. The aim is to determine regional balances of excess heat relative heat demands for all third level administrative regions in the European Union (EU) and to identify strategic regions suitable for large-scale implementation of district heating. The approach is motivated since the efficiency of current supply structures to meet building heat demands, mainly characterised by direct use of primary energy sources, is low and improvable. District heating is conceived as an urban supply side energy efficiency measure employable to enhance energy system efficiency by increased excess heat recoveries; hereby reducing primary energy demands by fuel substitution. However, the importance of heat has long been underestimated in EU decarbonisation strategies and local heat synergies have often been overlooked in energy models used for such scenarios. Study results indicate that 46% of all excess heat in EU27, corresponding to 31% of total building heat demands, is located within identified strategic regions. Still, a realisation of these rich opportunities will require higher recognition of the heat sector in future EU energy policy. - Highlights: • EU27 energy and industry sector heat recycling resources are mapped and quantified. • Target regions for large-scale implementation of district heating are identified. • 46% of total EU27 excess heat volume is seized in 63 strategic heat synergy regions. • Large urban zones have lead roles to play in transition to sustainability in Europe. • Higher recognition of heat sector is needed in future EU energy policy for realisation

  14. Regional functionality of the cerebellum

    NARCIS (Netherlands)

    Witter, Laurens; De Zeeuw, Chris I

    2015-01-01

    Over the recent years, advances in brain imaging, optogenetics and viral tracing have greatly advanced our understanding of the cerebellum and its connectivity. It has become clear that the cerebellum can be divided into functional units, each connected with particular brain areas involved in

  15. Activation of different cerebral functional regions following ...

    African Journals Online (AJOL)

    Background: To explore the brain function regions characteristics of the acupoint combination, this study observed activity changes in the brain regions of healthy volunteers after acupuncture at both Taixi (KI3) and Taichong (LR3) (KI3 + LR3) and KI3 alone using resting-state functional magnetic resonance imaging(fMRI).

  16. Identifying revealed comparative advantages in an EU regional context

    OpenAIRE

    Cordes, Alexander; Gehrke, Birgit; Römisch, Roman; Rammer, Christian; Schliessler, Paula; Wassmann, Pia

    2015-01-01

    [Introduction ...] Overall, this report is structured as follows: the next chapter (2) briefly outlines the relevance of regional trade indicators for determining the competitiveness of a region. In chapter 3, the methodology for the calculation of regional trade performance indicators is introduced, and the elementary results are described. Chapter 4 presents an econometric analysis relating key regional characteristics to international success of local industries. Based upon the regional di...

  17. Data mining a functional neuroimaging database for functional segregation in brain regions

    DEFF Research Database (Denmark)

    Nielsen, Finn Årup; Balslev, Daniela; Hansen, Lars Kai

    2006-01-01

    We describe a specialized neuroinformatic data mining technique in connection with a meta-analytic functional neuroimaging database: We mine for functional segregation within brain regions by identifying journal articles that report brain activations within the regions and clustering the abstract...

  18. Data mining a functional neuroimaging database for functional|segregation in brain regions

    DEFF Research Database (Denmark)

    Nielsen, Finn Årup

    2006-01-01

    We describe a specialized neuroinformatic data mining technique in connection with a meta-analytic functional neuroimaging database: We mine for functional segregation within brain regions by identifying journal articles that report brain activations within the regions and clustering the abstract...

  19. An Alternative Method for Identifying Interplanetary Magnetic Cloud Regions

    Energy Technology Data Exchange (ETDEWEB)

    Ojeda-Gonzalez, A.; Prestes, A.; Klausner, V. [Laboratory of Physics and Astronomy, IP and D/Universidade do Vale do Paraíba—UNIVAP, São José dos Campos, SP (Brazil); Mendes, O. [Division of Space Geophysics, National Institute for Space Research, São José dos Campos, SP (Brazil); Calzadilla, A. [Department of Space Geophysics, Institute of Geophysics and Astronomy, Havana (Cuba); Domingues, M. O., E-mail: ojeda.gonzalez.a@gmail.com [Associate Laboratory of Applied Computing and Mathematics, National Institute for Space Research, São José dos Campos, SP (Brazil)

    2017-03-10

    Spatio-temporal entropy (STE) analysis is used as an alternative mathematical tool to identify possible magnetic cloud (MC) candidates. We analyze Interplanetary Magnetic Field (IMF) data using a time interval of only 10 days. We select a convenient data interval of 2500 records moving forward by 200 record steps until the end of the time series. For every data segment, the STE is calculated at each step. During an MC event, the STE reaches values close to zero. This extremely low value of STE is due to MC structure features. However, not all of the magnetic components in MCs have STE values close to zero at the same time. For this reason, we create a standardization index (the so-called Interplanetary Entropy, IE, index). This index is a worthwhile effort to develop new tools to help diagnose ICME structures. The IE was calculated using a time window of one year (1999), and it has a success rate of 70% over other identifiers of MCs. The unsuccessful cases (30%) are caused by small and weak MCs. The results show that the IE methodology identified 9 of 13 MCs, and emitted nine false alarm cases. In 1999, a total of 788 windows of 2500 values existed, meaning that the percentage of false alarms was 1.14%, which can be considered a good result. In addition, four time windows, each of 10 days, are studied, where the IE method was effective in finding MC candidates. As a novel result, two new MCs are identified in these time windows.

  20. Regional specialization within the human striatum for diverse psychological functions.

    Science.gov (United States)

    Pauli, Wolfgang M; O'Reilly, Randall C; Yarkoni, Tal; Wager, Tor D

    2016-02-16

    Decades of animal and human neuroimaging research have identified distinct, but overlapping, striatal zones, which are interconnected with separable corticostriatal circuits, and are crucial for the organization of functional systems. Despite continuous efforts to subdivide the human striatum based on anatomical and resting-state functional connectivity, characterizing the different psychological processes related to each zone remains a work in progress. Using an unbiased, data-driven approach, we analyzed large-scale coactivation data from 5,809 human imaging studies. We (i) identified five distinct striatal zones that exhibited discrete patterns of coactivation with cortical brain regions across distinct psychological processes and (ii) identified the different psychological processes associated with each zone. We found that the reported pattern of cortical activation reliably predicted which striatal zone was most strongly activated. Critically, activation in each functional zone could be associated with distinct psychological processes directly, rather than inferred indirectly from psychological functions attributed to associated cortices. Consistent with well-established findings, we found an association of the ventral striatum (VS) with reward processing. Confirming less well-established findings, the VS and adjacent anterior caudate were associated with evaluating the value of rewards and actions, respectively. Furthermore, our results confirmed a sometimes overlooked specialization of the posterior caudate nucleus for executive functions, often considered the exclusive domain of frontoparietal cortical circuits. Our findings provide a precise functional map of regional specialization within the human striatum, both in terms of the differential cortical regions and psychological functions associated with each striatal zone.

  1. Modelling the regional application of stakeholder identified land management strategies.

    Science.gov (United States)

    Irvine, B. J.; Fleskens, L.; Kirkby, M. J.

    2012-04-01

    The DESIRE project has trialled a series of sustainable land management (SLM) technologies. These technologies have been identified as being beneficial in mitigating land degradation by local stakeholders from a range of semi-arid study sites. The field results and the qualitative WOCAT technology assessment ftom across the study sites have been used to develop the adapted PESERA SLM model. This paper considers the development of the adapted PESERA SLM model and the potential for applying locally successful SLM technologies across a wider range of climatic and environmental conditions with respect to degradation risk, biomass production and the investment cost interface (PESERA/DESMICE). The integrate PESERA/DESMICE model contributes to the policy debate by providing a biophysical and socio-economic assessment of technology and policy scenarios.

  2. Functional connectome fingerprinting: identifying individuals using patterns of brain connectivity.

    Science.gov (United States)

    Finn, Emily S; Shen, Xilin; Scheinost, Dustin; Rosenberg, Monica D; Huang, Jessica; Chun, Marvin M; Papademetris, Xenophon; Constable, R Todd

    2015-11-01

    Functional magnetic resonance imaging (fMRI) studies typically collapse data from many subjects, but brain functional organization varies between individuals. Here we establish that this individual variability is both robust and reliable, using data from the Human Connectome Project to demonstrate that functional connectivity profiles act as a 'fingerprint' that can accurately identify subjects from a large group. Identification was successful across scan sessions and even between task and rest conditions, indicating that an individual's connectivity profile is intrinsic, and can be used to distinguish that individual regardless of how the brain is engaged during imaging. Characteristic connectivity patterns were distributed throughout the brain, but the frontoparietal network emerged as most distinctive. Furthermore, we show that connectivity profiles predict levels of fluid intelligence: the same networks that were most discriminating of individuals were also most predictive of cognitive behavior. Results indicate the potential to draw inferences about single subjects on the basis of functional connectivity fMRI.

  3. Identifying and annotating human bifunctional RNAs reveals their versatile functions.

    Science.gov (United States)

    Chen, Geng; Yang, Juan; Chen, Jiwei; Song, Yunjie; Cao, Ruifang; Shi, Tieliu; Shi, Leming

    2016-10-01

    Bifunctional RNAs that possess both protein-coding and noncoding functional properties were less explored and poorly understood. Here we systematically explored the characteristics and functions of such human bifunctional RNAs by integrating tandem mass spectrometry and RNA-seq data. We first constructed a pipeline to identify and annotate bifunctional RNAs, leading to the characterization of 132 high-confidence bifunctional RNAs. Our analyses indicate that bifunctional RNAs may be involved in human embryonic development and can be functional in diverse tissues. Moreover, bifunctional RNAs could interact with multiple miRNAs and RNA-binding proteins to exert their corresponding roles. Bifunctional RNAs may also function as competing endogenous RNAs to regulate the expression of many genes by competing for common targeting miRNAs. Finally, somatic mutations of diverse carcinomas may generate harmful effect on corresponding bifunctional RNAs. Collectively, our study not only provides the pipeline for identifying and annotating bifunctional RNAs but also reveals their important gene-regulatory functions.

  4. Identifying functions for ex-core neutron noise analysis

    International Nuclear Information System (INIS)

    Avila, J.M.; Oliveira, J.C.

    1987-01-01

    A method of performing the phase analysis of signals arising from neutron detectors placed in the periphery of a pressurized water reactor is proposed. It consists in the definition of several identifying functions, based on the phases of cross power spectral densities corresponding to four ex-core neutron detectors. Each of these functions enhances the appearance of different sources of noise. The method, applied to the ex-core neutron fluctuation analysis of a French PWR, proved to be very useful as it allows quick recognition of various patterns in the power spectral densities. (orig.) [de

  5. Determining coding CpG islands by identifying regions significant for pattern statistics on Markov chains.

    Science.gov (United States)

    Singer, Meromit; Engström, Alexander; Schönhuth, Alexander; Pachter, Lior

    2011-09-23

    Recent experimental and computational work confirms that CpGs can be unmethylated inside coding exons, thereby showing that codons may be subjected to both genomic and epigenomic constraint. It is therefore of interest to identify coding CpG islands (CCGIs) that are regions inside exons enriched for CpGs. The difficulty in identifying such islands is that coding exons exhibit sequence biases determined by codon usage and constraints that must be taken into account. We present a method for finding CCGIs that showcases a novel approach we have developed for identifying regions of interest that are significant (with respect to a Markov chain) for the counts of any pattern. Our method begins with the exact computation of tail probabilities for the number of CpGs in all regions contained in coding exons, and then applies a greedy algorithm for selecting islands from among the regions. We show that the greedy algorithm provably optimizes a biologically motivated criterion for selecting islands while controlling the false discovery rate. We applied this approach to the human genome (hg18) and annotated CpG islands in coding exons. The statistical criterion we apply to evaluating islands reduces the number of false positives in existing annotations, while our approach to defining islands reveals significant numbers of undiscovered CCGIs in coding exons. Many of these appear to be examples of functional epigenetic specialization in coding exons.

  6. IDENTIFYING REGIONAL CLUSTER MANAGEMENT POTENTIALS EMPIRICAL RESULTS FROM THREE NORTH RHINEWESTPHALIAN REGIONS

    OpenAIRE

    Rudiger Hamm; Christiane Goebel

    2010-01-01

    The development and support of clusters is an issue that became quite popular by players dealing with regional economic policy. But before a regional development agency can start to implement a cluster-oriented strategy there a two question that have to be answered: 1. What are the regional fields of competence (cluster potentials) that fulfill the requirements for a cluster-oriented regional development policy? 2. If you find such regional fields of competence, are the enterprises willing to...

  7. REGIONAL LOGISTICS CENTER: FORMATION AND FUNCTIONING SPESIFIC

    Directory of Open Access Journals (Sweden)

    Oleg Tkach

    2017-08-01

    Full Text Available In this article the essence of the definition of logistics centers is defined, the main provisions concerning the formation of the logistics center are defined. The formation of a logistic hub is analyzed. The structure of the transport-logistic center is proposed. The basic requirements for the location of the regional logistics center and the principles of its operation are determined. The financial and financial mechanism of a typical logistics center and their effective functioning are presented. It is proved that the most important component of the logistics center is transport. Key words: logistics centers, logistics, hub, distribution centers, transport and logistics centers, regional logistic centers, logistics complex, transport, transport-logistic system.

  8. Newer Approaches to Identify Potential Untoward Effects in Functional Foods.

    Science.gov (United States)

    Marone, Palma Ann; Birkenbach, Victoria L; Hayes, A Wallace

    2016-01-01

    Globalization has greatly accelerated the numbers and variety of food and beverage products available worldwide. The exchange among greater numbers of countries, manufacturers, and products in the United States and worldwide has necessitated enhanced quality measures for nutritional products for larger populations increasingly reliant on functionality. These functional foods, those that provide benefit beyond basic nutrition, are increasingly being used for their potential to alleviate food insufficiency while enhancing quality and longevity of life. In the United States alone, a steady import increase of greater than 15% per year or 24 million shipments, over 70% products of which are food related, is regulated under the Food and Drug Administration (FDA). This unparalleled growth has resulted in the need for faster, cheaper, and better safety and efficacy screening methods in the form of harmonized guidelines and recommendations for product standardization. In an effort to meet this need, the in vitro toxicology testing market has similarly grown with an anticipatory 15% increase between 2010 and 2015 of US$1.3 to US$2.7 billion. Although traditionally occupying a small fraction of the market behind pharmaceuticals and cosmetic/household products, the scope of functional food testing, including additives/supplements, ingredients, residues, contact/processing, and contaminants, is potentially expansive. Similarly, as functional food testing has progressed, so has the need to identify potential adverse factors that threaten the safety and quality of these products. © The Author(s) 2015.

  9. Drosophila Cancer Models Identify Functional Differences between Ret Fusions.

    Science.gov (United States)

    Levinson, Sarah; Cagan, Ross L

    2016-09-13

    We generated and compared Drosophila models of RET fusions CCDC6-RET and NCOA4-RET. Both RET fusions directed cells to migrate, delaminate, and undergo EMT, and both resulted in lethality when broadly expressed. In all phenotypes examined, NCOA4-RET was more severe than CCDC6-RET, mirroring their effects on patients. A functional screen against the Drosophila kinome and a library of cancer drugs found that CCDC6-RET and NCOA4-RET acted through different signaling networks and displayed distinct drug sensitivities. Combining data from the kinome and drug screens identified the WEE1 inhibitor AZD1775 plus the multi-kinase inhibitor sorafenib as a synergistic drug combination that is specific for NCOA4-RET. Our work emphasizes the importance of identifying and tailoring a patient's treatment to their specific RET fusion isoform and identifies a multi-targeted therapy that may prove effective against tumors containing the NCOA4-RET fusion. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants.

    Directory of Open Access Journals (Sweden)

    Mengmeng Du

    Full Text Available Genome-wide association studies (GWAS have identified many common single nucleotide polymorphisms (SNPs associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs. We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33. We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s.

  11. Clinical assessment tools identify functional deficits in fragility fracture patients

    Directory of Open Access Journals (Sweden)

    Ames TD

    2016-05-01

    Full Text Available Tyler D Ames,1 Corinne E Wee,1 Khoi M Le,1 Tiffany L Wang,1 Julie Y Bishop,2 Laura S Phieffer,2 Carmen E Quatman2 1The Ohio State University College of Medicine, 2Department of Orthopaedics, The Ohio State University Wexner Medical Center, Columbus, OH, USA Purpose: To identify inexpensive, noninvasive, portable, clinical assessment tools that can be used to assess functional performance measures that may put older patients at risk for falls such as balance, handgrip strength, and lumbopelvic control.Patients and methods: Twenty fragility fracture patients and 21 healthy control subjects were evaluated using clinical assessment tools (Nintendo Wii Balance Board [WBB], a handheld dynamometer, and an application for the Apple iPod Touch, the Level Belt that measure functional performance during activity of daily living tasks. The main outcome measurements were balance (WBB, handgrip strength (handheld dynamometer, and lumbopelvic control (iPod Touch Level Belt, which were compared between fragility fracture patients and healthy controls.Results: Fragility fracture patients had lower scores on the vertical component of the WBB Torso Twist task (P=0.042 and greater medial–lateral lumbopelvic sway during a 40 m walk (P=0.026 when compared to healthy controls. Unexpectedly, the fracture patients had significantly higher scores on the left leg (P=0.020 and total components (P=0.010 of the WBB Single Leg Stand task as well as less faults during the left Single Leg Stand task (P=0.003.Conclusion: The clinical assessment tools utilized in this study are relatively inexpensive and portable tools of performance measures capable of detecting differences in postural sway between fragility fracture patients and controls. Keywords: fall risk, geriatric fracture, Nintendo Wii Balance Board, Level Belt, fragility fracture

  12. Functional evaluation of the anorectal region

    International Nuclear Information System (INIS)

    Pomerri, F.; Curtolo, S.; Muzzio, P.C.; Pittarello, F.; Dodi, G.

    1991-01-01

    Defecography is a method allowing the morphodynamic evaluation of the anorectal region. The technique needs two complementary times: 'phase' defecography and dynamic defecography. In the series of patients affected with severe constipation, 2 groups could be identified. Group A included those patients (mean age: 38.7 years) in whom no significant changes were observed in anorectal angle from pubococcygeal line in comparison with normal subjects (student's t-test). Group B included those patients (mean age : 63.3 years) in whom significant reduction was observed in anorectal angle on straining, together with increased distance of anorectal angle from pubococcygeal line on squeezing in comparison with normal subjects (Students t-test). In constipated patients narrowed anal canal was observed (60%), together with rectocele (42.6%), mucosal prolapse (27.8%), rectal prolapse (18%) and solitary ulcer (14.7%). In idiopathic incontonence patients (mean age: 63.3 years), increased distance was observed of anorectal angle from pubococcygeal line on squeezing, in the most severe cases, even at rest, with the patient sitting (Student's t-test). In incontinent patients larger anal canal was observed (67.6%), together with rectocele (36.7%), mucosal prolapse (14.7%), and rectal prolapse (11.7%)

  13. Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions.

    Science.gov (United States)

    Xie, Hongbo; Vucetic, Slobodan; Iakoucheva, Lilia M; Oldfield, Christopher J; Dunker, A Keith; Uversky, Vladimir N; Obradovic, Zoran

    2007-05-01

    Identifying relationships between function, amino acid sequence, and protein structure represents a major challenge. In this study, we propose a bioinformatics approach that identifies functional keywords in the Swiss-Prot database that correlate with intrinsic disorder. A statistical evaluation is employed to rank the significance of these correlations. Protein sequence data redundancy and the relationship between protein length and protein structure were taken into consideration to ensure the quality of the statistical inferences. Over 200,000 proteins from the Swiss-Prot database were analyzed using this approach. The predictions of intrinsic disorder were carried out using PONDR VL3E predictor of long disordered regions that achieves an accuracy of above 86%. Overall, out of the 710 Swiss-Prot functional keywords that were each associated with at least 20 proteins, 238 were found to be strongly positively correlated with predicted long intrinsically disordered regions, whereas 302 were strongly negatively correlated with such regions. The remaining 170 keywords were ambiguous without strong positive or negative correlation with the disorder predictions. These functions cover a large variety of biological activities and imply that disordered regions are characterized by a wide functional repertoire. Our results agree well with literature findings, as we were able to find at least one illustrative example of functional disorder or order shown experimentally for the vast majority of keywords showing the strongest positive or negative correlation with intrinsic disorder. This work opens a series of three papers, which enriches the current view of protein structure-function relationships, especially with regards to functionalities of intrinsically disordered proteins, and provides researchers with a novel tool that could be used to improve the understanding of the relationships between protein structure and function. The first paper of the series describes our

  14. Functional Anthology of Intrinsic Disorder. I. Biological Processes and Functions of Proteins with Long Disordered Regions

    Science.gov (United States)

    Xie, Hongbo; Vucetic, Slobodan; Iakoucheva, Lilia M.; Oldfield, Christopher J.; Dunker, A. Keith; Uversky, Vladimir N.; Obradovic, Zoran

    2008-01-01

    Identifying relationships between function, amino acid sequence and protein structure represents a major challenge. In this study we propose a bioinformatics approach that identifies functional keywords in the Swiss-Prot database that correlate with intrinsic disorder. A statistical evaluation is employed to rank the significance of these correlations. Protein sequence data redundancy and the relationship between protein length and protein structure were taken into consideration to ensure the quality of the statistical inferences. Over 200,000 proteins from Swiss-Prot database were analyzed using this approach. The predictions of intrinsic disorder were carried out using PONDR VL3E predictor of long disordered regions that achieves an accuracy of above 86%. Overall, out of the 710 Swiss-Prot functional keywords that were each associated with at least 20 proteins, 238 were found to be strongly positively correlated with predicted long intrinsically disordered regions, whereas 302 were strongly negatively correlated with such regions. The remaining 170 keywords were ambiguous without strong positive or negative correlation with the disorder predictions. These functions cover a large variety of biological activities and imply that disordered regions are characterized by a wide functional repertoire. Our results agree well with literature findings, as we were able to find at least one illustrative example of functional disorder or order shown experimentally for the vast majority of keywords showing the strongest positive or negative correlation with intrinsic disorder. This work opens a series of three papers, which enriches the current view of protein structure-function relationships, especially with regards to functionalities of intrinsically disordered proteins and provides researchers with a novel tool that could be used to improve the understanding of the relationships between protein structure and function. The first paper of the series describes our statistical

  15. Motor Functions of the Broca's Region

    Science.gov (United States)

    Binkofski, Ferdinand; Buccino, Giovanni

    2004-01-01

    Broca's region in the dominant cerebral hemisphere is known to mediate the production of language but also contributes to comprehension. This region evolved only in humans and is constituted of Brodmann's areas 44 and 45 in the inferior frontal gyrus. There is, however, evidence that Broca's region overlaps, at least in part, with the ventral…

  16. Can a structured questionnaire identify patients with reduced renal function?

    DEFF Research Database (Denmark)

    Azzouz, Manal; Rømsing, Janne; Thomsen, Henrik

    2014-01-01

    To evaluate a structured questionnaire in identifying outpatients with renal dysfunction before MRI or CT in various age groups.......To evaluate a structured questionnaire in identifying outpatients with renal dysfunction before MRI or CT in various age groups....

  17. Immunochip analysis identifies association of the RAD50/IL13 region with human longevity.

    Science.gov (United States)

    Flachsbart, Friederike; Ellinghaus, David; Gentschew, Liljana; Heinsen, Femke-Anouska; Caliebe, Amke; Christiansen, Lene; Nygaard, Marianne; Christensen, Kaare; Blanché, Hélène; Deleuze, Jean-François; Derbois, Céline; Galan, Pilar; Büning, Carsten; Brand, Stephan; Peters, Anette; Strauch, Konstantin; Müller-Nurasyid, Martina; Hoffmann, Per; Nöthen, Markus M; Lieb, Wolfgang; Franke, Andre; Schreiber, Stefan; Nebel, Almut

    2016-06-01

    Human longevity is characterized by a remarkable lack of confirmed genetic associations. Here, we report on the identification of a novel locus for longevity in the RAD50/IL13 region on chromosome 5q31.1 using a combined European sample of 3208 long-lived individuals (LLI) and 8919 younger controls. First, we performed a large-scale association study on 1458 German LLI (mean age 99.0 years) and 6368 controls (mean age 57.2 years) by targeting known immune-associated loci covered by the Immunochip. The analysis of 142 136 autosomal single nucleotide polymorphisms (SNPs) revealed an Immunochip-wide significant signal (PI mmunochip  = 7.01 × 10(-9) ) for the SNP rs2075650 in the TOMM40/APOE region, which has been previously described in the context of human longevity. To identify novel susceptibility loci, we selected 15 markers with PI mmunochip  association at SNP rs2706372 replicated in the French study collection and showed a similar trend in the Danish participants and was also significant in a meta-analysis of the combined French and Danish data after adjusting for multiple testing. In a meta-analysis of all three samples, rs2706372 reached a P-value of PI mmunochip+Repl  = 5.42 × 10(-7) (OR = 1.20; 95% CI = 1.12-1.28). SNP rs2706372 is located in the extended RAD50/IL13 region. RAD50 seems a plausible longevity candidate due to its involvement in DNA repair and inflammation. Further studies are needed to identify the functional variant(s) that predispose(s) to a long and healthy life. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  18. H-1 Nuclear Magnetic Resonance Metabolomics Analysis Identifies Novel Urinary Biomarkers for Lung Function

    International Nuclear Information System (INIS)

    McClay, Joseph L.; Adkins, Daniel E.; Isern, Nancy G.; O'Connell, Thomas M.; Wooten, Jan B.; Zedler, Barbara K.; Dasika, Madhukar S.; Webb, B.T.; Webb-Robertson, Bobbie-Jo M.; Pounds, Joel G.; Murrelle, Edward L.; Leppert, Mark F.; van den Oord, Edwin J.

    2010-01-01

    Chronic obstructive pulmonary disease (COPD), characterized by chronic airflow limitation, is a serious and growing public health concern. The major environmental risk factor for COPD is tobacco smoking, but the biological mechanisms underlying COPD are not well understood. In this study, we used proton nuclear magnetic resonance (1H-NMR) spectroscopy to identify and quantify metabolites associated with lung function in COPD. Plasma and urine were collected from 197 adults with COPD and from 195 adults without COPD. Samples were assayed using a 600 MHz NMR spectrometer, and the resulting spectra were analyzed against quantitative spirometric measures of lung function. After correcting for false discoveries and adjusting for covariates (sex, age, smoking) several spectral regions in urine were found to be significantly associated with baseline lung function. These regions correspond to the metabolites trigonelline, hippurate and formate. Concentrations of each metabolite, standardized to urinary creatinine, were associated with baseline lung function (minimum p-value = 0.0002 for trigonelline). No significant associations were found with plasma metabolites. Two of the three urinary metabolites positively associated with baseline lung function, i.e. hippurate and formate, are often related to gut microflora. This suggests that the microbiome composition is variable between individuals with different lung function. Alternatively, the nature and origins of all three associated metabolites may reflect lifestyle differences affecting overall health. Our results will require replication and validation, but demonstrate the utility of NMR metabolomics as a screening tool for identifying novel biomarkers of lung disease or disease risk.

  19. Knock-In Mice with NOP-eGFP Receptors Identify Receptor Cellular and Regional Localization.

    Science.gov (United States)

    Ozawa, Akihiko; Brunori, Gloria; Mercatelli, Daniela; Wu, Jinhua; Cippitelli, Andrea; Zou, Bende; Xie, Xinmin Simon; Williams, Melissa; Zaveri, Nurulain T; Low, Sarah; Scherrer, Grégory; Kieffer, Brigitte L; Toll, Lawrence

    2015-08-19

    The nociceptin/orphanin FQ (NOP) receptor, the fourth member of the opioid receptor family, is involved in many processes common to the opioid receptors including pain and drug abuse. To better characterize receptor location and trafficking, knock-in mice were created by inserting the gene encoding enhanced green fluorescent protein (eGFP) into the NOP receptor gene (Oprl1) and producing mice expressing a functional NOP-eGFP C-terminal fusion in place of the native NOP receptor. The NOP-eGFP receptor was present in brain of homozygous knock-in animals in concentrations somewhat higher than in wild-type mice and was functional when tested for stimulation of [(35)S]GTPγS binding in vitro and in patch-clamp electrophysiology in dorsal root ganglia (DRG) neurons and hippocampal slices. Inhibition of morphine analgesia was equivalent when tested in knock-in and wild-type mice. Imaging revealed detailed neuroanatomy in brain, spinal cord, and DRG and was generally consistent with in vitro autoradiographic imaging of receptor location. Multicolor immunohistochemistry identified cells coexpressing various spinal cord and DRG cellular markers, as well as coexpression with μ-opioid receptors in DRG and brain regions. Both in tissue slices and primary cultures, the NOP-eGFP receptors appear throughout the cell body and in processes. These knock-in mice have NOP receptors that function both in vitro and in vivo and appear to be an exceptional tool to study receptor neuroanatomy and correlate with NOP receptor function. The NOP receptor, the fourth member of the opioid receptor family, is involved in pain, drug abuse, and a number of other CNS processes. The regional and cellular distribution has been difficult to determine due to lack of validated antibodies for immunohistochemical analysis. To provide a new tool for the investigation of receptor localization, we have produced knock-in mice with a fluorescent-tagged NOP receptor in place of the native NOP receptor. These

  20. Identifying Similarities in Cognitive Subtest Functional Requirements: An Empirical Approach

    Science.gov (United States)

    Frisby, Craig L.; Parkin, Jason R.

    2007-01-01

    In the cognitive test interpretation literature, a Rational/Intuitive, Indirect Empirical, or Combined approach is typically used to construct conceptual taxonomies of the functional (behavioral) similarities between subtests. To address shortcomings of these approaches, the functional requirements for 49 subtests from six individually…

  1. Identifying the molecular functions of electron transport proteins using radial basis function networks and biochemical properties.

    Science.gov (United States)

    Le, Nguyen-Quoc-Khanh; Nguyen, Trinh-Trung-Duong; Ou, Yu-Yen

    2017-05-01

    The electron transport proteins have an important role in storing and transferring electrons in cellular respiration, which is the most proficient process through which cells gather energy from consumed food. According to the molecular functions, the electron transport chain components could be formed with five complexes with several different electron carriers and functions. Therefore, identifying the molecular functions in the electron transport chain is vital for helping biologists understand the electron transport chain process and energy production in cells. This work includes two phases for discriminating electron transport proteins from transport proteins and classifying categories of five complexes in electron transport proteins. In the first phase, the performances from PSSM with AAIndex feature set were successful in identifying electron transport proteins in transport proteins with achieved sensitivity of 73.2%, specificity of 94.1%, and accuracy of 91.3%, with MCC of 0.64 for independent data set. With the second phase, our method can approach a precise model for identifying of five complexes with different molecular functions in electron transport proteins. The PSSM with AAIndex properties in five complexes achieved MCC of 0.51, 0.47, 0.42, 0.74, and 1.00 for independent data set, respectively. We suggest that our study could be a power model for determining new proteins that belongs into which molecular function of electron transport proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. OXPHOS-Dependent Cells Identify Environmental Disruptors of Mitochondrial Function

    Science.gov (United States)

    Mitochondrial dysfunction is associated with numerous chronic diseases including metabolic syndrome. Environmental chemicals can impair mitochondrial function through numerous mechanisms such as membrane disruption, complex inhibition and electron transport chain uncoupling. Curr...

  3. A probabilistic approach to delineating functional brain regions

    DEFF Research Database (Denmark)

    Kalbitzer, Jan; Svarer, Claus; Frokjaer, Vibe G

    2009-01-01

    The purpose of this study was to develop a reliable observer-independent approach to delineating volumes of interest (VOIs) for functional brain regions that are not identifiable on structural MR images. The case is made for the raphe nuclei, a collection of nuclei situated in the brain stem known...... to be densely packed with serotonin transporters (5-hydroxytryptaminic [5-HTT] system). METHODS: A template set for the raphe nuclei, based on their high content of 5-HTT as visualized in parametric (11)C-labeled 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile PET images, was created for 10...... healthy subjects. The templates were subsequently included in the region sets used in a previously published automatic MRI-based approach to create an observer- and activity-independent probabilistic VOI map. The probabilistic map approach was tested in a different group of 10 subjects and compared...

  4. Information sensitivity functions to assess parameter information gain and identifiability of dynamical systems.

    Science.gov (United States)

    Pant, Sanjay

    2018-05-01

    A new class of functions, called the 'information sensitivity functions' (ISFs), which quantify the information gain about the parameters through the measurements/observables of a dynamical system are presented. These functions can be easily computed through classical sensitivity functions alone and are based on Bayesian and information-theoretic approaches. While marginal information gain is quantified by decrease in differential entropy, correlations between arbitrary sets of parameters are assessed through mutual information. For individual parameters, these information gains are also presented as marginal posterior variances, and, to assess the effect of correlations, as conditional variances when other parameters are given. The easy to interpret ISFs can be used to (a) identify time intervals or regions in dynamical system behaviour where information about the parameters is concentrated; (b) assess the effect of measurement noise on the information gain for the parameters; (c) assess whether sufficient information in an experimental protocol (input, measurements and their frequency) is available to identify the parameters; (d) assess correlation in the posterior distribution of the parameters to identify the sets of parameters that are likely to be indistinguishable; and (e) assess identifiability problems for particular sets of parameters. © 2018 The Authors.

  5. Sensing a Sensor: Identifying the Mechanosensory Function of Primary Cilia

    Science.gov (United States)

    Prasad, Rahul M.; Jin, Xingjian; Nauli, Surya M.

    2014-01-01

    Over the past decade, primary cilia have emerged as the premier means by which cells sense and transduce mechanical stimuli. Primary cilia are sensory organelles that have been shown to be vitally involved in the mechanosensation of urine in the renal nephron, bile in the hepatic biliary system, digestive fluid in the pancreatic duct, dentin in dental pulp, lacunocanalicular fluid in bone and cartilage, and blood in vasculature. The prevalence of primary cilia among mammalian cell types is matched by the tremendously varied disease states caused by both structural and functional defects in cilia. In the process of delineating the mechanisms behind these disease states, calcium fluorimetry has been widely utilized as a means of quantifying ciliary function to both fluid flow and pharmacological agents. In this review, we will discuss the approaches used in associating calcium levels to cilia function. PMID:24839551

  6. Sensing a Sensor: Identifying the Mechanosensory Function of Primary Cilia

    Directory of Open Access Journals (Sweden)

    Rahul M. Prasad

    2014-03-01

    Full Text Available Over the past decade, primary cilia have emerged as the premier means by which cells sense and transduce mechanical stimuli. Primary cilia are sensory organelles that have been shown to be vitally involved in the mechanosensation of urine in the renal nephron, bile in the hepatic biliary system, digestive fluid in the pancreatic duct, dentin in dental pulp, lacunocanalicular fluid in bone and cartilage, and blood in vasculature. The prevalence of primary cilia among mammalian cell types is matched by the tremendously varied disease states caused by both structural and functional defects in cilia. In the process of delineating the mechanisms behind these disease states, calcium fluorimetry has been widely utilized as a means of quantifying ciliary function to both fluid flow and pharmacological agents. In this review, we will discuss the approaches used in associating calcium levels to cilia function.

  7. The FUN of identifying gene function in bacterial pathogens; insights from Salmonella functional genomics.

    Science.gov (United States)

    Hammarlöf, Disa L; Canals, Rocío; Hinton, Jay C D

    2013-10-01

    The availability of thousands of genome sequences of bacterial pathogens poses a particular challenge because each genome contains hundreds of genes of unknown function (FUN). How can we easily discover which FUN genes encode important virulence factors? One solution is to combine two different functional genomic approaches. First, transcriptomics identifies bacterial FUN genes that show differential expression during the process of mammalian infection. Second, global mutagenesis identifies individual FUN genes that the pathogen requires to cause disease. The intersection of these datasets can reveal a small set of candidate genes most likely to encode novel virulence attributes. We demonstrate this approach with the Salmonella infection model, and propose that a similar strategy could be used for other bacterial pathogens. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. LUMINOSITY FUNCTIONS OF SPITZER-IDENTIFIED PROTOSTARS IN NINE NEARBY MOLECULAR CLOUDS

    Energy Technology Data Exchange (ETDEWEB)

    Kryukova, E.; Megeath, S. T.; Allen, T. S. [Department of Physics and Astronomy, University of Toledo, Toledo, OH (United States); Gutermuth, R. A. [Department of Astronomy, University of Massachusetts, Amherst, MA (United States); Pipher, J. [Department of Physics and Astronomy, University of Rochester, Rochester, NY (United States); Allen, L. E. [National Optical Astronomy Observatories, Tucson, AZ (United States); Myers, P. C. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA (United States); Muzerolle, J. [Space Telescope Science Institute, Baltimore, MD (United States)

    2012-08-15

    We identify protostars in Spitzer surveys of nine star-forming (SF) molecular clouds within 1 kpc: Serpens, Perseus, Ophiuchus, Chamaeleon, Lupus, Taurus, Orion, Cep OB3, and Mon R2, which combined host over 700 protostar candidates. These clouds encompass a variety of SF environments, including both low-mass and high-mass SF regions, as well as dense clusters and regions of sparsely distributed star formation. Our diverse cloud sample allows us to compare protostar luminosity functions in these varied environments. We combine near- and mid-infrared photometry from the Two Micron All Sky Survey and Spitzer to create 1-24 {mu}m spectral energy distributions (SEDs). Using protostars from the c2d survey with well-determined bolometric luminosities, we derive a relationship between bolometric luminosity, mid-IR luminosity (integrated from 1-24 {mu}m), and SED slope. Estimations of the bolometric luminosities for protostar candidates are combined to create luminosity functions for each cloud. Contamination due to edge-on disks, reddened Class II sources, and galaxies is estimated and removed from the luminosity functions. We find that luminosity functions for high-mass SF clouds (Orion, Mon R2, and Cep OB3) peak near 1 L{sub Sun} and show a tail extending toward luminosities above 100 L{sub Sun }. The luminosity functions of the low-mass SF clouds (Serpens, Perseus, Ophiuchus, Taurus, Lupus, and Chamaeleon) do not exhibit a common peak, however the combined luminosity function of these regions peaks below 1 L{sub Sun }. Finally, we examine the luminosity functions as a function of the local surface density of young stellar objects. In the Orion molecular clouds, we find a significant difference between the luminosity functions of protostars in regions of high and low stellar density, the former of which is biased toward more luminous sources. This may be the result of primordial mass segregation, although this interpretation is not unique. We compare our luminosity

  9. LUMINOSITY FUNCTIONS OF SPITZER-IDENTIFIED PROTOSTARS IN NINE NEARBY MOLECULAR CLOUDS

    International Nuclear Information System (INIS)

    Kryukova, E.; Megeath, S. T.; Allen, T. S.; Gutermuth, R. A.; Pipher, J.; Allen, L. E.; Myers, P. C.; Muzerolle, J.

    2012-01-01

    We identify protostars in Spitzer surveys of nine star-forming (SF) molecular clouds within 1 kpc: Serpens, Perseus, Ophiuchus, Chamaeleon, Lupus, Taurus, Orion, Cep OB3, and Mon R2, which combined host over 700 protostar candidates. These clouds encompass a variety of SF environments, including both low-mass and high-mass SF regions, as well as dense clusters and regions of sparsely distributed star formation. Our diverse cloud sample allows us to compare protostar luminosity functions in these varied environments. We combine near- and mid-infrared photometry from the Two Micron All Sky Survey and Spitzer to create 1-24 μm spectral energy distributions (SEDs). Using protostars from the c2d survey with well-determined bolometric luminosities, we derive a relationship between bolometric luminosity, mid-IR luminosity (integrated from 1-24 μm), and SED slope. Estimations of the bolometric luminosities for protostar candidates are combined to create luminosity functions for each cloud. Contamination due to edge-on disks, reddened Class II sources, and galaxies is estimated and removed from the luminosity functions. We find that luminosity functions for high-mass SF clouds (Orion, Mon R2, and Cep OB3) peak near 1 L ☉ and show a tail extending toward luminosities above 100 L ☉ . The luminosity functions of the low-mass SF clouds (Serpens, Perseus, Ophiuchus, Taurus, Lupus, and Chamaeleon) do not exhibit a common peak, however the combined luminosity function of these regions peaks below 1 L ☉ . Finally, we examine the luminosity functions as a function of the local surface density of young stellar objects. In the Orion molecular clouds, we find a significant difference between the luminosity functions of protostars in regions of high and low stellar density, the former of which is biased toward more luminous sources. This may be the result of primordial mass segregation, although this interpretation is not unique. We compare our luminosity functions to those

  10. Identifying hotspots and management of critical ecosystem services in rapidly urbanizing Yangtze River Delta Region, China.

    Science.gov (United States)

    Cai, Wenbo; Gibbs, David; Zhang, Lang; Ferrier, Graham; Cai, Yongli

    2017-04-15

    Rapid urbanization has altered many ecosystems, causing a decline in many ecosystem services, generating serious ecological crisis. To cope with these challenges, we presented a comprehensive framework comprising five core steps for identifying and managing hotspots of critical ecosystem services in a rapid urbanizing region. This framework was applied in the case study of the Yangtze River Delta (YRD) Region. The study showed that there was large spatial heterogeneity in the hotspots of ecosystem services in the region, hotspots of supporting services and regulating services aggregately distributing in the southwest mountainous areas while hotspots of provisioning services mainly in the northeast plain, and hotspots of cultural services widespread in the waterbodies and southwest mountainous areas. The regionalization of the critical ecosystem services was made through the hotspot analysis. This study provided valuable information for environmental planning and management in a rapid urbanizing region and helped improve China's ecological redlines policy at regional scale. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Quantitation of global and regional left ventricular function by MRI

    NARCIS (Netherlands)

    van der Geest, RJ; Reiber, JHC; Reiber, JHC; VanDerWall, EE

    1998-01-01

    Magnetic resonance imaging (MRI) provides several imaging strategies for assessing left ventricular function. As a three-dimensional imaging technique, all measurements can be performed without relying on geometrical assumptions. Global and regional function parameters can be derived from

  12. Computational approaches to identify functional genetic variants in cancer genomes

    DEFF Research Database (Denmark)

    Gonzalez-Perez, Abel; Mustonen, Ville; Reva, Boris

    2013-01-01

    The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor but only a minority of these drive tumor progression. We present the result of discu......The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor but only a minority of these drive tumor progression. We present the result...... of discussions within the ICGC on how to address the challenge of identifying mutations that contribute to oncogenesis, tumor maintenance or response to therapy, and recommend computational techniques to annotate somatic variants and predict their impact on cancer phenotype....

  13. Gene expression meta-analysis identifies chromosomal regions involved in ovarian cancer survival

    DEFF Research Database (Denmark)

    Thomassen, Mads; Jochumsen, Kirsten M; Mogensen, Ole

    2009-01-01

    the relation of gene expression and chromosomal position to identify chromosomal regions of importance for early recurrence of ovarian cancer. By use of *Gene Set Enrichment Analysis*, we have ranked chromosomal regions according to their association to survival. Over-representation analysis including 1...... using death (P = 0.015) and recurrence (P = 0.002) as outcome. The combined mutation score is strongly associated to upregulation of several growth factor pathways....

  14. Probing molecular mechanisms of the Hsp90 chaperone: biophysical modeling identifies key regulators of functional dynamics.

    Directory of Open Access Journals (Sweden)

    Anshuman Dixit

    Full Text Available Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based "conformational selection" of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected

  15. Regional lung function evaluation with nitrogen-13

    Energy Technology Data Exchange (ETDEWEB)

    Ahluwalia, B; Brownell, G L; Hales, C; Kazemi, H

    1981-10-01

    Regional ventilation and perfusion studies are routinely performed with molecular nitrogen-13 (a short-lived positron emitter), a multicrystal positron camera, and a computer. These studies have the advantage of viewing with equal sensitivity all sections of the lung simultaneously. Nitrogen-13 is less soluble than xenon in blood and therefore allows more accurate ventilation imaging. The short half-life of the radiopharmaceutical allows simultaneous ventilation and perfusion scintigraphy of the lung. Unlike other imaging techniques in which the residual radioactivity persists in the lung for hours, nitrogen-13 is rapidly cleared allowing repetitive imaging. Ventilation and perfusion studies are part of the routine preoperative evaluation for lung cancer resection or for bullectomy in patients with chronic obstructive pulmonary disease and for assessment of pulmonary emboli in the presence of chronic obstructive disease.

  16. Array Manipulation And Matrix-Tree Method To Identify High Concentration Regions HCRs

    Directory of Open Access Journals (Sweden)

    Rachana Arora

    2015-08-01

    Full Text Available Abstract-Sequence Alignment and Analysis is one of the most important applications of bioinformatics. It involves alignment a pair or more sequences with each other and identify a common pattern that would ultimately lead to conclusions of homology or dissimilarity. A number of algorithms that make use of dynamic programming to perform alignment between sequences are available. One of their main disadvantages is that they involve complicated computations and backtracking methods that are difficult to implement. This paper describes a much simpler method to identify common regions in 2 sequences and align them based on the density of common sequences identified.

  17. Identifying regions of interest in medical images using self-organizing maps.

    Science.gov (United States)

    Teng, Wei-Guang; Chang, Ping-Lin

    2012-10-01

    Advances in data acquisition, processing and visualization techniques have had a tremendous impact on medical imaging in recent years. However, the interpretation of medical images is still almost always performed by radiologists. Developments in artificial intelligence and image processing have shown the increasingly great potential of computer-aided diagnosis (CAD). Nevertheless, it has remained challenging to develop a general approach to process various commonly used types of medical images (e.g., X-ray, MRI, and ultrasound images). To facilitate diagnosis, we recommend the use of image segmentation to discover regions of interest (ROI) using self-organizing maps (SOM). We devise a two-stage SOM approach that can be used to precisely identify the dominant colors of a medical image and then segment it into several small regions. In addition, by appropriately conducting the recursive merging steps to merge smaller regions into larger ones, radiologists can usually identify one or more ROIs within a medical image.

  18. Use of macroinvertebrates to identify cultivated wetlands in the Prairie Pothole Region

    Science.gov (United States)

    Euliss, Ned H.; Mushet, David M.; Johnson, Douglas H.

    2001-01-01

    We evaluated the use of macroinvertebrates as a potential tool to identify dry and intensively farmed temporary and seasonal wetlands in the Prairie Pothole Region. The techniques we designed and evaluated used the dried remains of invertebrates or their egg banks in soils as indicators of wetlands. For both the dried remains of invertebrates and their egg banks, we weighted each taxon according to its affinity for wetlands or uplands. Our study clearly demonstrated that shells, exoskeletons, head capsules, eggs, and other remains of macroinvertebrates can be used to identify wetlands, even when they are dry, intensively farmed, and difficult to identify as wetlands using standard criteria (i.e., hydrology, hydrophytic vegetation, and hydric soils). Although both dried remains and egg banks identified wetlands, the combination was more useful, especially for identifying drained or filled wetlands. We also evaluated the use of coarse taxonomic groupings to stimulate use of the technique by nonspecialists and obtained satisfactory results in most situations.

  19. Differential activation of an identified motor neuron and neuromodulation provide Aplysia's retractor muscle an additional function.

    Science.gov (United States)

    McManus, Jeffrey M; Lu, Hui; Cullins, Miranda J; Chiel, Hillel J

    2014-08-15

    To survive, animals must use the same peripheral structures to perform a variety of tasks. How does a nervous system employ one muscle to perform multiple functions? We addressed this question through work on the I3 jaw muscle of the marine mollusk Aplysia californica's feeding system. This muscle mediates retraction of Aplysia's food grasper in multiple feeding responses and is innervated by a pool of identified neurons that activate different muscle regions. One I3 motor neuron, B38, is active in the protraction phase, rather than the retraction phase, suggesting the muscle has an additional function. We used intracellular, extracellular, and muscle force recordings in several in vitro preparations as well as recordings of nerve and muscle activity from intact, behaving animals to characterize B38's activation of the muscle and its activity in different behavior types. We show that B38 specifically activates the anterior region of I3 and is specifically recruited during one behavior, swallowing. The function of this protraction-phase jaw muscle contraction is to hold food; thus the I3 muscle has an additional function beyond mediating retraction. We additionally show that B38's typical activity during in vivo swallowing is insufficient to generate force in an unmodulated muscle and that intrinsic and extrinsic modulation shift the force-frequency relationship to allow contraction. Using methods that traverse levels from individual neuron to muscle to intact animal, we show how regional muscle activation, differential motor neuron recruitment, and neuromodulation are key components in Aplysia's generation of multifunctionality. Copyright © 2014 the American Physiological Society.

  20. Normalization of the collage regions of iterated function systems

    Science.gov (United States)

    Zhang, Zhengbing; Zhang, Wei

    2012-11-01

    Fractal graphics, generated with iterated function systems (IFS), have been applied in broad areas. Since the collage regions of different IFS may be different, it is difficult to respectively show the attractors of iterated function systems in a same region on a computer screen using one program without modifying the display parameters. An algorithm is proposed in this paper to solve this problem. A set of transforms are repeatedly applied to modify the coefficients of the IFS so that the collage region of the resulted IFS changes toward the unit square. Experimental results demonstrate that the collage region of any IFS can be normalized to the unit square with the proposed method.

  1. Identify fracture-critical regions inside the proximal femur using statistical parametric mapping

    Science.gov (United States)

    Li, Wenjun; Kornak, John; Harris, Tamara; Keyak, Joyce; Li, Caixia; Lu, Ying; Cheng, Xiaoguang; Lang, Thomas

    2009-01-01

    We identified regions inside the proximal femur that are most strongly associated with hip fracture. Bone densitometry based on such fracture-critical regions showed improved power in discriminating fracture patients from controls. Introduction Hip fractures typically occur in lateral falls, with focal mechanical failure of the sub-volumes of tissue in which the applied stress exceeds the strength. In this study, we describe a new methodology to identify proximal femoral tissue elements with highest association with hip fracture. We hypothesize that bone mineral density (BMD) measured in such sub-volumes discriminates hip fracture risk better than BMD in standard anatomic regions such as the femoral neck and trochanter. Materials and Methods We employed inter-subject registration to transform hip QCT images of 37 patients with hip fractures and 38 age-matched controls into a voxel-based statistical atlas. Within voxels, we performed t-tests between the two groups to identify the regions which differed most. We then randomly divided the 75 scans into a training set and a test set. From the training set, we derived a fracture-driven region of interest (ROI) based on association with fracture. In the test set, we measured BMD in this ROI to determine fracture discrimination efficacy using ROC analysis. Additionally, we compared the BMD distribution differences between the 29 patients with neck fractures and the 8 patients with trochanteric fractures. Results By evaluating fracture discrimination power based on ROC analysis, the fracture-driven ROI had an AUC (area under curve) of 0.92, while anatomic ROIs (including the entire proximal femur, the femoral neck, trochanter and their cortical and trabecular compartments) had AUC values between 0.78 and 0.87. We also observed that the neck fracture patients had lower BMD (p=0.014) in a small region near the femoral neck and the femoral head, and patients with trochanteric fractures had lower BMD in trochanteric regions

  2. Chronnectome fingerprinting: Identifying individuals and predicting higher cognitive functions using dynamic brain connectivity patterns.

    Science.gov (United States)

    Liu, Jin; Liao, Xuhong; Xia, Mingrui; He, Yong

    2018-02-01

    The human brain is a large, interacting dynamic network, and its architecture of coupling among brain regions varies across time (termed the "chronnectome"). However, very little is known about whether and how the dynamic properties of the chronnectome can characterize individual uniqueness, such as identifying individuals as a "fingerprint" of the brain. Here, we employed multiband resting-state functional magnetic resonance imaging data from the Human Connectome Project (N = 105) and a sliding time-window dynamic network analysis approach to systematically examine individual time-varying properties of the chronnectome. We revealed stable and remarkable individual variability in three dynamic characteristics of brain connectivity (i.e., strength, stability, and variability), which was mainly distributed in three higher order cognitive systems (i.e., default mode, dorsal attention, and fronto-parietal) and in two primary systems (i.e., visual and sensorimotor). Intriguingly, the spatial patterns of these dynamic characteristics of brain connectivity could successfully identify individuals with high accuracy and could further significantly predict individual higher cognitive performance (e.g., fluid intelligence and executive function), which was primarily contributed by the higher order cognitive systems. Together, our findings highlight that the chronnectome captures inherent functional dynamics of individual brain networks and provides implications for individualized characterization of health and disease. © 2017 Wiley Periodicals, Inc.

  3. Genome-wide methylation analysis identified sexually dimorphic methylated regions in hybrid tilapia

    Science.gov (United States)

    Wan, Zi Yi; Xia, Jun Hong; Lin, Grace; Wang, Le; Lin, Valerie C. L.; Yue, Gen Hua

    2016-01-01

    Sexual dimorphism is an interesting biological phenomenon. Previous studies showed that DNA methylation might play a role in sexual dimorphism. However, the overall picture of the genome-wide methylation landscape in sexually dimorphic species remains unclear. We analyzed the DNA methylation landscape and transcriptome in hybrid tilapia (Oreochromis spp.) using whole genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-seq). We found 4,757 sexually dimorphic differentially methylated regions (DMRs), with significant clusters of DMRs located on chromosomal regions associated with sex determination. CpG methylation in promoter regions was negatively correlated with the gene expression level. MAPK/ERK pathway was upregulated in male tilapia. We also inferred active cis-regulatory regions (ACRs) in skeletal muscle tissues from WGBS datasets, revealing sexually dimorphic cis-regulatory regions. These results suggest that DNA methylation contribute to sex-specific phenotypes and serve as resources for further investigation to analyze the functions of these regions and their contributions towards sexual dimorphisms. PMID:27782217

  4. TRANSFER-FUNCTIONS OF A LINEARIZED MULTI-REGION REACTOR

    Energy Technology Data Exchange (ETDEWEB)

    Higgins, Thomas J.

    1963-09-15

    The development of the transfer functions for a linearized multi-region reactor is studied, and an illustration is made of application of the corresponding theory by a numerical illustrative example. (auth)

  5. A method of identifying social structures in siting regions for deep geological repositories in Switzerland

    International Nuclear Information System (INIS)

    Brander, Simone

    2010-09-01

    Acceptance is a key element in the site selection process for deep geological repositories for high-level and low and intermediate-level radioactive waste in Switzerland. Participation requirements such as comprehensive negotiation issues and adequate resources have thus been defined by the Swiss Federal Office of Energy (SFOE). In 2008, on the basis of technical criteria Nagra (National Cooperative for the Disposal of Radioactive Waste) proposed several potential areas for deep geological repositories. The number of potential areas will be narrowed down within the next few years. All municipalities within the planning perimeter (the area in which surface facilities can be realised) are affected and form the siting region. In order to ensure that the local population have their say in the forthcoming discussions, regional participation bodies including all municipalities within a siting region are being set up by the SFOE. Regional participation ensures that local interests, needs and values are taken into account in the site selection process. Assembling the regional participation bodies is therefore of great importance. Before such bodies can be formed, however, the various interests, needs and values have to be identified, and special attention has to be paid to long-term interests of future generations, as well as to non-organised and under-represented interests. According to the concept of proportional representation, the interests, needs and values that are identified and weighted by the local population are to be represented in the regional participation procedure. The aim of this study is to share a method of mapping existing social structures in a defined geographical area. This involves a combination of an analysis of socio-economic statistical data and qualitative and quantitative social research methods

  6. Bilingualism alters brain functional connectivity between "control" regions and "language" regions: Evidence from bimodal bilinguals.

    Science.gov (United States)

    Li, Le; Abutalebi, Jubin; Zou, Lijuan; Yan, Xin; Liu, Lanfang; Feng, Xiaoxia; Wang, Ruiming; Guo, Taomei; Ding, Guosheng

    2015-05-01

    Previous neuroimaging studies have revealed that bilingualism induces both structural and functional neuroplasticity in the dorsal anterior cingulate cortex (dACC) and the left caudate nucleus (LCN), both of which are associated with cognitive control. Since these "control" regions should work together with other language regions during language processing, we hypothesized that bilingualism may also alter the functional interaction between the dACC/LCN and language regions. Here we tested this hypothesis by exploring the functional connectivity (FC) in bimodal bilinguals and monolinguals using functional MRI when they either performed a picture naming task with spoken language or were in resting state. We found that for bimodal bilinguals who use spoken and sign languages, the FC of the dACC with regions involved in spoken language (e.g. the left superior temporal gyrus) was stronger in performing the task, but weaker in the resting state as compared to monolinguals. For the LCN, its intrinsic FC with sign language regions including the left inferior temporo-occipital part and right inferior and superior parietal lobules was increased in the bilinguals. These results demonstrate that bilingual experience may alter the brain functional interaction between "control" regions and "language" regions. For different control regions, the FC alters in different ways. The findings also deepen our understanding of the functional roles of the dACC and LCN in language processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Identifying open magnetic field regions of the Sun and their heliospheric counterparts

    Science.gov (United States)

    Krista, L. D.; Reinard, A.

    2017-12-01

    Open magnetic regions on the Sun are either long-lived (coronal holes) or transient (dimmings) in nature. Both phenomena are fundamental to our understanding of the solar behavior as a whole. Coronal holes are the sources of high-speed solar wind streams that cause recurrent geomagnetic storms. Furthermore, the variation of coronal hole properties (area, location, magnetic field strength) over the solar activity cycle is an important marker of the global evolution of the solar magnetic field. Dimming regions, on the other hand, are short-lived coronal holes that often emerge in the wake of solar eruptions. By analyzing their physical properties and their temporal evolution, we aim to understand their connection with their eruptive counterparts (flares and coronal mass ejections) and predict the possibility of a geomagnetic storm. The author developed the Coronal Hole Automated Recognition and Monitoring (CHARM) and the Coronal Dimming Tracker (CoDiT) algorithms. These tools not only identify but track the evolution of open magnetic field regions. CHARM also provides daily coronal hole maps, that are used for forecasts at the NOAA Space Weather Prediction Center. Our goal is to better understand the processes that give rise to eruptive and non-eruptive open field regions and investigate how these regions evolve over time and influence space weather.

  8. Regional lung function (133Xe-radiospirometry) in bronchial cancer

    International Nuclear Information System (INIS)

    Arborelius, M.; Kristersson, S.; Lindell, S.E.

    1976-01-01

    In a prospective study of all patients with bronchial cancer in the city of Malmoe, all patients considered for surgery were examined with regard to overall function (conventional spirometry) and regional lung function (133-Xe-radiospirometry). Out of 116 consecutive cases examined with 133-Xe-radiospirometry before surgery,

  9. Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization.

    Science.gov (United States)

    Laffin, Jennifer J S; Raca, Gordana; Jackson, Craig A; Strand, Edythe A; Jakielski, Kathy J; Shriberg, Lawrence D

    2012-11-01

    The goal of this study was to identify new candidate genes and genomic copy-number variations associated with a rare, severe, and persistent speech disorder termed childhood apraxia of speech. Childhood apraxia of speech is the speech disorder segregating with a mutation in FOXP2 in a multigenerational London pedigree widely studied for its role in the development of speech-language in humans. A total of 24 participants who were suspected to have childhood apraxia of speech were assessed using a comprehensive protocol that samples speech in challenging contexts. All participants met clinical-research criteria for childhood apraxia of speech. Array comparative genomic hybridization analyses were completed using a customized 385K Nimblegen array (Roche Nimblegen, Madison, WI) with increased coverage of genes and regions previously associated with childhood apraxia of speech. A total of 16 copy-number variations with potential consequences for speech-language development were detected in 12 or half of the 24 participants. The copy-number variations occurred on 10 chromosomes, 3 of which had two to four candidate regions. Several participants were identified with copy-number variations in two to three regions. In addition, one participant had a heterozygous FOXP2 mutation and a copy-number variation on chromosome 2, and one participant had a 16p11.2 microdeletion and copy-number variations on chromosomes 13 and 14. Findings support the likelihood of heterogeneous genomic pathways associated with childhood apraxia of speech.

  10. Regional zooplankton dispersal provides spatial insurance for ecosystem function.

    Science.gov (United States)

    Symons, Celia C; Arnott, Shelley E

    2013-05-01

    Changing environmental conditions are affecting diversity and ecosystem function globally. Theory suggests that dispersal from a regional species pool may buffer against changes in local community diversity and ecosystem function after a disturbance through the establishment of functionally redundant tolerant species. The spatial insurance provided by dispersal may decrease through time after environmental change as the local community monopolizes resources and reduces community invasibility. To test for evidence of the spatial insurance hypothesis and to determine the role dispersal timing plays in this response we conducted a field experiment using crustacean zooplankton communities in a subarctic region that is expected to be highly impacted by climate change - Churchill, Canada. Three experiments were conducted where nutrients, salt, and dispersal were manipulated. The three experiments differed in time-since-disturbance that the dispersers were added. We found that coarse measures of diversity (i.e. species richness, evenness, and Shannon-Weiner diversity) were generally resistant to large magnitude disturbances, and that dispersal had the most impact on diversity when dispersers were added shortly after disturbance. Ecosystem functioning (chl-a) was degraded in disturbed communities, but dispersal recovered ecosystem function to undisturbed levels. This spatial insurance for ecosystem function was mediated through changes in community composition and the relative abundance of functional groups. Results suggest that regional diversity and habitat connectivity will be important in the future to maintain ecosystem function by introducing functionally redundant species to promote compensatory dynamics. © 2012 Blackwell Publishing Ltd.

  11. Functionally distinct amygdala subregions identified using DTI and high-resolution fMRI

    Science.gov (United States)

    Balderston, Nicholas L.; Schultz, Douglas H.; Hopkins, Lauren

    2015-01-01

    Although the amygdala is often directly linked with fear and emotion, amygdala neurons are activated by a wide variety of emotional and non-emotional stimuli. Different subregions within the amygdala may be engaged preferentially by different aspects of emotional and non-emotional tasks. To test this hypothesis, we measured and compared the effects of novelty and fear on amygdala activity. We used high-resolution blood oxygenation level-dependent (BOLD) imaging and streamline tractography to subdivide the amygdala into three distinct functional subunits. We identified a laterobasal subregion connected with the visual cortex that responds generally to visual stimuli, a non-projecting region that responds to salient visual stimuli, and a centromedial subregion connected with the diencephalon that responds only when a visual stimulus predicts an aversive outcome. We provide anatomical and functional support for a model of amygdala function where information enters through the laterobasal subregion, is processed by intrinsic circuits in the interspersed tissue, and is then passed to the centromedial subregion, where activation leads to behavioral output. PMID:25969533

  12. Using an International Clinical Registry of Regional Anesthesia to Identify Targets for Quality Improvement

    Science.gov (United States)

    Sites, Brian D.; Barrington, Michael J.; Davis, Matthew

    2014-01-01

    Background Despite the widespread use of regional anesthesia, limited information on clinical performance exists. Institutions, therefore, have little knowledge of how they are performing in regards to both safety and effectiveness. In this study, we demonstrate how a medical institution (or physician/physician group) may use data from a multi-center clinical registry of regional anesthesia to inform quality improvement strategies. Methods We analyzed data from the International Registry of Regional Anesthesia that includes prospective data on peripheral regional anesthesia procedures from 19 centers located around the world. Using data from the clinical registry, we present summary statistics of the overall safety and effectiveness of regional anesthesia. Furthermore, we demonstrate, using a variety of performance measures, how these data can be used by hospitals to identify areas for quality improvement. To do so, we compare the performance of one member institution (a United States medical center in New Hampshire) to that of the other 18 member institutions of the clinical registry. Results The clinical registry contained information on 23,271 blocks that were performed between June 1, 2011, and May 1, 2014, on 16,725 patients. The overall success rate was 96.7%, immediate complication rate was 2.2%, and the all-cause 60-day rate of neurological sequelae was 8.3 (95% CI, 7.2–9.7) per 10,000. Registry wide major hospital events included 7 wrong site blocks, 3 seizures, 1 complete heart block, 1 retroperitoneal hematoma, and 3 pneumothoraces. For our reference medical center, we identified areas meriting quality improvement. Specifically, after accounting for differences in the age, sex, and health status of patient populations, the reference medical center appeared to rely more heavily on opioids for post procedure management, had higher patient pain scores, and experienced delayed discharge when compared with other member institutions. Conclusions To our

  13. Green's function matching method for adjoining regions having different masses

    International Nuclear Information System (INIS)

    Morgenstern Horing, Norman J

    2006-01-01

    We present a primer on the method of Green's function matching for the determination of the global Schroedinger Green's function for all space subject to joining conditions at an interface between two (or more) separate parts of the region having different masses. The object of this technique is to determine the full space Schroedinger Green's function in terms of the individual Green's functions of the constituent parts taken as if they were themselves extended to all space. This analytical method has had successful applications in the theory of surface states, and remains of interest for nanostructures

  14. Application of Geomorphologic Factors for Identifying Soil Loss in Vulnerable Regions of the Cameron Highlands

    Directory of Open Access Journals (Sweden)

    Kahhoong Kok

    2018-03-01

    Full Text Available The main purpose of this study is to propose a methodology for identifying vulnerable regions in the Cameron Highlands that are susceptible to soil loss, based on runoff aggregation structure and the energy expenditure pattern of the natural river basin, within the framework of power law distribution. To this end, three geomorphologic factors, namely shear stress and stream power, as well as the drainage area of every point in the basin of interest, have been extracted using GIS, and then their complementary cumulative distributions are graphically analyzed by fitting them to power law distribution, with the purpose of identifying the sensitive points within the basin that are susceptible to soil loss with respect to scaling regimes of shear stress and stream power. It is observed that the range of vulnerable regions by the scaling regime of shear stress is much narrower than by the scaling regime of stream power. This result seems to suggest that shear stress is a scale-dependent factor, which does not follow power law distribution and does not adequately reflect the energy expenditure pattern of a river basin. Therefore, stream power is preferred as a more reasonable factor for the evaluation of soil loss. The methodology proposed in this study can be validated by visualizing the path of soil loss, which is generated from the hillslope process (characterized by the local slope to the valley through a fluvial process (characterized by the drainage area as well as the local slope.

  15. Bat Accelerated Regions Identify a Bat Forelimb Specific Enhancer in the HoxD Locus.

    Directory of Open Access Journals (Sweden)

    Betty M Booker

    2016-03-01

    Full Text Available The molecular events leading to the development of the bat wing remain largely unknown, and are thought to be caused, in part, by changes in gene expression during limb development. These expression changes could be instigated by variations in gene regulatory enhancers. Here, we used a comparative genomics approach to identify regions that evolved rapidly in the bat ancestor, but are highly conserved in other vertebrates. We discovered 166 bat accelerated regions (BARs that overlap H3K27ac and p300 ChIP-seq peaks in developing mouse limbs. Using a mouse enhancer assay, we show that five Myotis lucifugus BARs drive gene expression in the developing mouse limb, with the majority showing differential enhancer activity compared to the mouse orthologous BAR sequences. These include BAR116, which is located telomeric to the HoxD cluster and had robust forelimb expression for the M. lucifugus sequence and no activity for the mouse sequence at embryonic day 12.5. Developing limb expression analysis of Hoxd10-Hoxd13 in Miniopterus natalensis bats showed a high-forelimb weak-hindlimb expression for Hoxd10-Hoxd11, similar to the expression trend observed for M. lucifugus BAR116 in mice, suggesting that it could be involved in the regulation of the bat HoxD complex. Combined, our results highlight novel regulatory regions that could be instrumental for the morphological differences leading to the development of the bat wing.

  16. Pooled-DNA sequencing identifies genomic regions of selection in Nigerian isolates of Plasmodium falciparum.

    Science.gov (United States)

    Oyebola, Kolapo M; Idowu, Emmanuel T; Olukosi, Yetunde A; Awolola, Taiwo S; Amambua-Ngwa, Alfred

    2017-06-29

    The burden of falciparum malaria is especially high in sub-Saharan Africa. Differences in pressure from host immunity and antimalarial drugs lead to adaptive changes responsible for high level of genetic variations within and between the parasite populations. Population-specific genetic studies to survey for genes under positive or balancing selection resulting from drug pressure or host immunity will allow for refinement of interventions. We performed a pooled sequencing (pool-seq) of the genomes of 100 Plasmodium falciparum isolates from Nigeria. We explored allele-frequency based neutrality test (Tajima's D) and integrated haplotype score (iHS) to identify genes under selection. Fourteen shared iHS regions that had at least 2 SNPs with a score > 2.5 were identified. These regions code for genes that were likely to have been under strong directional selection. Two of these genes were the chloroquine resistance transporter (CRT) on chromosome 7 and the multidrug resistance 1 (MDR1) on chromosome 5. There was a weak signature of selection in the dihydrofolate reductase (DHFR) gene on chromosome 4 and MDR5 genes on chromosome 13, with only 2 and 3 SNPs respectively identified within the iHS window. We observed strong selection pressure attributable to continued chloroquine and sulfadoxine-pyrimethamine use despite their official proscription for the treatment of uncomplicated malaria. There was also a major selective sweep on chromosome 6 which had 32 SNPs within the shared iHS region. Tajima's D of circumsporozoite protein (CSP), erythrocyte-binding antigen (EBA-175), merozoite surface proteins - MSP3 and MSP7, merozoite surface protein duffy binding-like (MSPDBL2) and serine repeat antigen (SERA-5) were 1.38, 1.29, 0.73, 0.84 and 0.21, respectively. We have demonstrated the use of pool-seq to understand genomic patterns of selection and variability in P. falciparum from Nigeria, which bears the highest burden of infections. This investigation identified known

  17. Plant functional traits and diversity in sand dune ecosystems across different biogeographic regions

    Science.gov (United States)

    Mahdavi, P.; Bergmeier, E.

    2016-07-01

    Plant species of a functional group respond similarly to environmental pressures and may be expected to act similarly on ecosystem processes and habitat properties. However, feasibility and applicability of functional groups in ecosystems across very different climatic regions have not yet been studied. In our approach we specified the functional groups in sand dune ecosystems of the Mediterranean, Hyrcanian and Irano-Turanian phytogeographic regions. We examined whether functional groups are more influenced by region or rather by habitat characteristics, and identified trait syndromes associated with common habitat types in sand dunes (mobile dunes, stabilized dunes, salt marshes, semi-wet sands, disturbed habitats). A database of 14 traits, 309 species and 314 relevés was examined and trait-species, trait-plot and species-plot matrices were built. Cluster analysis revealed similar plant functional groups in sand dune ecosystems across regions of very different species composition and climate. Specifically, our study showed that plant traits in sand dune ecosystems are grouped reflecting habitat affiliation rather than region and species pool. Environmental factors and constraints such as sand mobility, soil salinity, water availability, nutrient status and disturbance are more important for the occurrence and distribution of plant functional groups than regional belonging. Each habitat is shown to be equipped with specific functional groups and can be described by specific sets of traits. In restoration ecology the completeness of functional groups and traits in a site may serve as a guideline for maintaining or restoring the habitat.

  18. Study of regional lung function with xenon 133

    International Nuclear Information System (INIS)

    Devaux, D.; Wagner, R.; Germain, M.; Chardon, G.

    1975-01-01

    Exploration of regional lung function includes study of the closed circuit perfusion and ventilation respectively by injection and inhalation of xenon 133. The radiation is measured across the chest using 4 fixed scintillation counters, placed opposite the subject's back, 2 per lung field. Theoretical regional values using 15 normal young subjects are determined. Three cases justified the practical interest of this method. The percentage of variation for the parameters studied was about 10%. The method proved very useful for the clinician to whom it provides a numerical assessment of regional ventilation and perfusion [fr

  19. Assessment of the Tourism Function in Region Development

    Directory of Open Access Journals (Sweden)

    Nataliia Zigern-Korn

    2014-07-01

    Full Text Available This article represents methodical approaches to estimation of tourism value and function in Russian regions development and contains some results of the carried-out assessment. The reasons about tourism mission for different types of territory exploitation and level of social and economic development, the idea of methods of tourist development of regions space are the core lines of the assessment framework. Selection of model regions due to their development types formed information basis for assessment. We determined specific Indicators and algorithm of an assessment to each model region. Results of the carried-out assessment allow rethinking the category of tourist and recreational potential of the territory from the standpoint of prospects and principles of a sustainable development. The technique of such impact assessment of tourism on regional development opens opportunity for public authorities to adopt correct strategic decisions according to the principles of Smart Development.

  20. Differentiating functional brain regions using optical coherence tomography (Conference Presentation)

    Science.gov (United States)

    Gil, Daniel A.; Bow, Hansen C.; Shen, Jin-H.; Joos, Karen M.; Skala, Melissa C.

    2017-02-01

    The human brain is made up of functional regions governing movement, sensation, language, and cognition. Unintentional injury during neurosurgery can result in significant neurological deficits and morbidity. The current standard for localizing function to brain tissue during surgery, intraoperative electrical stimulation or recording, significantly increases the risk, time, and cost of the procedure. There is a need for a fast, cost-effective, and high-resolution intraoperative technique that can avoid damage to functional brain regions. We propose that optical coherence tomography (OCT) can fill this niche by imaging differences in the cellular composition and organization of functional brain areas. We hypothesized this would manifest as differences in the attenuation coefficient measured using OCT. Five functional regions (prefrontal, somatosensory, auditory, visual, and cerebellum) were imaged in ex vivo porcine brains (n=3), a model chosen due to a similar white/gray matter ratio as human brains. The attenuation coefficient was calculated using a depth-resolved model and quantitatively validated with Intralipid phantoms across a physiological range of attenuation coefficients (absolute difference Nissl-stained histology will be used to validate our results and correlate OCT-measured attenuation coefficients to neuronal density. Additional development and validation of OCT algorithms to discriminate brain regions are planned to improve the safety and efficacy of neurosurgical procedures such as biopsy, electrode placement, and tissue resection.

  1. REGIONAL FEATURES OF ENTREPRENEURSHIP FUNCTIONING IN THE AGRARIAN SPHERE

    OpenAIRE

    Tyumerova I. B.

    2014-01-01

    The article analyzes the activities of the agrarian sphere in the Chuvash Republic; we have also developed a matrix of opportunities for the development of the agrarian sector in conjunction with the entrepreneurship, entrepreneurial development strategy identified the cluster as the main factor of socio-economic development of the region

  2. Identification of Flood Reactivity Regions via the Functional Clustering of Hydrographs

    Science.gov (United States)

    Brunner, Manuela I.; Viviroli, Daniel; Furrer, Reinhard; Seibert, Jan; Favre, Anne-Catherine

    2018-03-01

    Flood hydrograph shapes contain valuable information on the flood-generation mechanisms of a catchment. To make good use of this information, we express flood hydrograph shapes as continuous functions using a functional data approach. We propose a clustering approach based on functional data for flood hydrograph shapes to identify a set of representative hydrograph shapes on a catchment scale and use these catchment-specific sets of representative hydrographs to establish regions of catchments with similar flood reactivity on a regional scale. We applied this approach to flood samples of 163 medium-size Swiss catchments. The results indicate that three representative hydrograph shapes sufficiently describe the hydrograph shape variability within a catchment and therefore can be used as a proxy for the flood behavior of a catchment. These catchment-specific sets of three hydrographs were used to group the catchments into three reactivity regions of similar flood behavior. These regions were not only characterized by similar hydrograph shapes and reactivity but also by event magnitudes and triggering event conditions. We envision these regions to be useful in regionalization studies, regional flood frequency analyses, and to allow for the construction of synthetic design hydrographs in ungauged catchments. The clustering approach based on functional data which establish these regions is very flexible and has the potential to be extended to other geographical regions or toward the use in climate impact studies.

  3. A novel data mining method to identify assay-specific signatures in functional genomic studies

    Directory of Open Access Journals (Sweden)

    Guidarelli Jack W

    2006-08-01

    Full Text Available Abstract Background: The highly dimensional data produced by functional genomic (FG studies makes it difficult to visualize relationships between gene products and experimental conditions (i.e., assays. Although dimensionality reduction methods such as principal component analysis (PCA have been very useful, their application to identify assay-specific signatures has been limited by the lack of appropriate methodologies. This article proposes a new and powerful PCA-based method for the identification of assay-specific gene signatures in FG studies. Results: The proposed method (PM is unique for several reasons. First, it is the only one, to our knowledge, that uses gene contribution, a product of the loading and expression level, to obtain assay signatures. The PM develops and exploits two types of assay-specific contribution plots, which are new to the application of PCA in the FG area. The first type plots the assay-specific gene contribution against the given order of the genes and reveals variations in distribution between assay-specific gene signatures as well as outliers within assay groups indicating the degree of importance of the most dominant genes. The second type plots the contribution of each gene in ascending or descending order against a constantly increasing index. This type of plots reveals assay-specific gene signatures defined by the inflection points in the curve. In addition, sharp regions within the signature define the genes that contribute the most to the signature. We proposed and used the curvature as an appropriate metric to characterize these sharp regions, thus identifying the subset of genes contributing the most to the signature. Finally, the PM uses the full dataset to determine the final gene signature, thus eliminating the chance of gene exclusion by poor screening in earlier steps. The strengths of the PM are demonstrated using a simulation study, and two studies of real DNA microarray data – a study of

  4. Functional connectivity decreases in autism in emotion, self, and face circuits identified by Knowledge-based Enrichment Analysis.

    Science.gov (United States)

    Cheng, Wei; Rolls, Edmund T; Zhang, Jie; Sheng, Wenbo; Ma, Liang; Wan, Lin; Luo, Qiang; Feng, Jianfeng

    2017-03-01

    A powerful new method is described called Knowledge based functional connectivity Enrichment Analysis (KEA) for interpreting resting state functional connectivity, using circuits that are functionally identified using search terms with the Neurosynth database. The method derives its power by focusing on neural circuits, sets of brain regions that share a common biological function, instead of trying to interpret single functional connectivity links. This provides a novel way of investigating how task- or function-related networks have resting state functional connectivity differences in different psychiatric states, provides a new way to bridge the gap between task and resting-state functional networks, and potentially helps to identify brain networks that might be treated. The method was applied to interpreting functional connectivity differences in autism. Functional connectivity decreases at the network circuit level in 394 patients with autism compared with 473 controls were found in networks involving the orbitofrontal cortex, anterior cingulate cortex, middle temporal gyrus cortex, and the precuneus, in networks that are implicated in the sense of self, face processing, and theory of mind. The decreases were correlated with symptom severity. Copyright © 2017. Published by Elsevier Inc.

  5. Validation of the ITS2 region as a novel DNA barcode for identifying medicinal plant species.

    Science.gov (United States)

    Chen, Shilin; Yao, Hui; Han, Jianping; Liu, Chang; Song, Jingyuan; Shi, Linchun; Zhu, Yingjie; Ma, Xinye; Gao, Ting; Pang, Xiaohui; Luo, Kun; Li, Ying; Li, Xiwen; Jia, Xiaocheng; Lin, Yulin; Leon, Christine

    2010-01-07

    The plant working group of the Consortium for the Barcode of Life recommended the two-locus combination of rbcL+matK as the plant barcode, yet the combination was shown to successfully discriminate among 907 samples from 550 species at the species level with a probability of 72%. The group admits that the two-locus barcode is far from perfect due to the low identification rate, and the search is not over. Here, we compared seven candidate DNA barcodes (psbA-trnH, matK, rbcL, rpoC1, ycf5, ITS2, and ITS) from medicinal plant species. Our ranking criteria included PCR amplification efficiency, differential intra- and inter-specific divergences, and the DNA barcoding gap. Our data suggest that the second internal transcribed spacer (ITS2) of nuclear ribosomal DNA represents the most suitable region for DNA barcoding applications. Furthermore, we tested the discrimination ability of ITS2 in more than 6600 plant samples belonging to 4800 species from 753 distinct genera and found that the rate of successful identification with the ITS2 was 92.7% at the species level. The ITS2 region can be potentially used as a standard DNA barcode to identify medicinal plants and their closely related species. We also propose that ITS2 can serve as a novel universal barcode for the identification of a broader range of plant taxa.

  6. Identifying Regional Key Eco-Space to Maintain Ecological Security Using GIS

    Directory of Open Access Journals (Sweden)

    Hualin Xie

    2014-02-01

    Full Text Available Ecological security and environmental sustainability are the foundations of sustainable development. With the acceleration of urbanization, increasing human activities have promoted greater impacts on the eco-spaces that maintain ecological security. Regional key eco-space has become the primary need to maintain environmental sustainability and can offer society with continued ecosystem services. In this paper, considering the security of water resources, biodiversity conservation, disaster avoidance and protection and natural recreation, an integrated index of eco-space importance was established and a method for identifying key eco-space was created using GIS, with Lanzhou City, China as a case study. The results show that the area of core eco-space in the Lanzhou City is approximately 50,908.7 hm2, accounting for 40% of the region’s total area. These areas mainly consist of geological hazard protection zones and the core zones of regional river systems, wetlands, nature reserves, forest parks and scenic spots. The results of this study provide some guidance for the management of ecological security, ecological restoration and environmental sustainability.

  7. Genome-wide association study identified CNP12587 region underlying height variation in Chinese females.

    Directory of Open Access Journals (Sweden)

    Yin-Ping Zhang

    Full Text Available Human height is a highly heritable trait considered as an important factor for health. There has been limited success in identifying the genetic factors underlying height variation. We aim to identify sequence variants associated with adult height by a genome-wide association study of copy number variants (CNVs in Chinese.Genome-wide CNV association analyses were conducted in 1,625 unrelated Chinese adults and sex specific subgroup for height variation, respectively. Height was measured with a stadiometer. Affymetrix SNP6.0 genotyping platform was used to identify copy number polymorphisms (CNPs. We constructed a genomic map containing 1,009 CNPs in Chinese individuals and performed a genome-wide association study of CNPs with height.We detected 10 significant association signals for height (p<0.05 in the whole population, 9 and 11 association signals for Chinese female and male population, respectively. A copy number polymorphism (CNP12587, chr18:54081842-54086942, p = 2.41 × 10(-4 was found to be significantly associated with height variation in Chinese females even after strict Bonferroni correction (p = 0.048. Confirmatory real time PCR experiments lent further support for CNV validation. Compared to female subjects with two copies of the CNP, carriers of three copies had an average of 8.1% decrease in height. An important candidate gene, ubiquitin-protein ligase NEDD4-like (NEDD4L, was detected at this region, which plays important roles in bone metabolism by binding to bone formation regulators.Our findings suggest the important genetic variants underlying height variation in Chinese.

  8. Genome-wide association identifies multiple genomic regions associated with susceptibility to and control of ovine lentivirus.

    Directory of Open Access Journals (Sweden)

    Stephen N White

    Full Text Available BACKGROUND: Like human immunodeficiency virus (HIV, ovine lentivirus (OvLV is macrophage-tropic and causes lifelong infection. OvLV infects one quarter of U.S. sheep and induces pneumonia and body condition wasting. There is no vaccine to prevent OvLV infection and no cost-effective treatment for infected animals. However, breed differences in prevalence and proviral concentration have indicated a genetic basis for susceptibility to OvLV. A recent study identified TMEM154 variants in OvLV susceptibility. The objective here was to identify additional loci associated with odds and/or control of OvLV infection. METHODOLOGY/PRINCIPAL FINDINGS: This genome-wide association study (GWAS included 964 sheep from Rambouillet, Polypay, and Columbia breeds with serological status and proviral concentration phenotypes. Analytic models accounted for breed and age, as well as genotype. This approach identified TMEM154 (nominal P=9.2×10(-7; empirical P=0.13, provided 12 additional genomic regions associated with odds of infection, and provided 13 regions associated with control of infection (all nominal P<1 × 10(-5. Rapid decline of linkage disequilibrium with distance suggested many regions included few genes each. Genes in regions associated with odds of infection included DPPA2/DPPA4 (empirical P=0.006, and SYTL3 (P=0.051. Genes in regions associated with control of infection included a zinc finger cluster (ZNF192, ZSCAN16, ZNF389, and ZNF165; P=0.001, C19orf42/TMEM38A (P=0.047, and DLGAP1 (P=0.092. CONCLUSIONS/SIGNIFICANCE: These associations provide targets for mutation discovery in sheep susceptibility to OvLV. Aside from TMEM154, these genes have not been associated previously with lentiviral infection in any species, to our knowledge. Further, data from other species suggest functional hypotheses for future testing of these genes in OvLV and other lentiviral infections. Specifically, SYTL3 binds and may regulate RAB27A, which is required for enveloped

  9. ESSENCE, STRUCTURE AND FUNCTIONS OF THE REGIONAL FINANCIAL SYSTEM

    Directory of Open Access Journals (Sweden)

    A. V. Milenkov

    2015-01-01

    Full Text Available The scientific themes of the article is relevant, as in the domestic and foreign economic literature, the term "financial system" does not comply with the fundamental theory of systems in which the system views revealed as a set of interrelated and interacting elements in accordance with the set to achieve the goal. Each of the elements of multi-level financial system has its own organizational structure, consisting of institutions and organizations within the jurisdiction of the entity government. In the article the author's interpretation of the concepts of "institutional framework," "organizational structure" of the regional financial system, defined the task of the financial system was to create rules and regulations of its operation, set out the basic functions of the institutions and organizations of the regional financial system, analyzes the external communication of the financial system, the implementation of which is one of the basic conditions for the effective functioning of the financial system in the region due to its inclusion in the federal and international financial sector. The contribution of the author in the development of the theme of the article is to specify and clarify the concepts of "the financial system", "institutional and organizational structure of the regional financial system," the development of methodological approaches to the formulation and use of methods of solving the institutional and organizational problems of the financial system in the region, the rationalization of the rules and regulations it current operation and future development, the definition of the composition of the basic functions that are adequate specialization and features of the institutes and organizations of the regional financial system.

  10. Functional characterization of rare missense mutations in MLH1 and MSH2 identified in Danish colorectal cancer patients

    DEFF Research Database (Denmark)

    Christensen, Lise Lotte; Kariola, Reetta; Korhonen, Mari K

    2009-01-01

    Recently, we have performed a population based study to analyse the frequency of colorectal cancer related MLH1 and MSH2 missense mutations in the Danish population. Half of the analyzed mutations were rare and most likely only present in the families where they were identified originally. Some...... of the missense mutations were located in conserved regions in the MLH1 and MSH2 proteins indicating a relation to disease development. In the present study, we functionally characterized 10 rare missense mutations in MLH1 and MSH2 identified in 13 Danish CRC families. To elucidate the pathogenicity...

  11. Word Frequency As a Cue For Identifying Function Words In Infancy

    Science.gov (United States)

    Hochmann, Jean-Remy; Endress, Ansgar D.; Mehler, Jacques

    2010-01-01

    While content words (e.g., 'dog') tend to carry meaning, function words (e.g., 'the') mainly serve syntactic purposes. Here, we ask whether 17-month old infants can use one language-universal cue to identify function word candidates: their high frequency of occurrence. In Experiment 1, infants listened to a series of short, naturally recorded…

  12. Changes in regional and overall lung function after bronchography

    International Nuclear Information System (INIS)

    Richez, M.; Ravez, P.; Godart, G.; Halloy, J.L.; Robience, Y.

    1980-01-01

    This investigation compares the effects of unilateral bronchography on classical pulmonary function paramerts (spirometry, CO transfer, flowvolume curve, and arterial blood gases)and radioisotopic measurements by means of 99 sup(m)Tc-labeled microspheres and 81 sup(m)Kr. The regional changes of ventilation and perfusion were quantified by a radioisotopic index, which was established for each zone of interest: explored lung and unexplored lung. The quantitative study of regional perfusion and ventilation reveals significant reduction of ventilation for lung bases, but not for lung apices. The radioisotopic measurements show a reduction of perfusion parallel to the reduction of ventilation. There is no significant correlation between traditional pulmonary function parameters and isotopic indices. Radioisotopy proved a sensitive tool for investigation of unilateral alterations. (orig.) [de

  13. Geological study for identifying potential aquifer zone in Pakes and Bandung Villages, Konang District, Bangkalan Region

    International Nuclear Information System (INIS)

    I Gde Sukadana

    2010-01-01

    Konang District has a problem on fresh water supply particularly in dry season. Two villages in the district, namely Pakes and Konang, are densely populated areas having agriculture activities, so available of sufficient fresh water is necessary. A fresh water source that can be developed in this area is deep groundwater source from potential aquifers. A geological study has been conducted to identify potential aquifer based on lithological aspect and geological structure. According to the regional stratigraphy. the study area consists of Tawun Formation and Ngrayong Formation. They compose of carbonaceous clay stone (the oldest rock unit), carbonaceous clay stone with sandy limestone intercalations, sandy limestone interbed with carbonaceous clay stone, tuff sandstone with clay stone intercalations, and reef limestone (the youngest) respectively. Strike and dip positions of the rocks layers are N110°E/22° - N150°E/26°, located on the south anticline axis with wavy plan to gentle slope of hilly morphology. Among the rock unit, only sandy limestone has fine sand with sub angular in shape and open pack. Qualitatively. this rock has good porosity and permeability and is enables to save and to flow subsurface water. Thus. the sandy limestone is considered as a potential zone for fresh water resources. Whereas, carbonaceous clay stone with clay grain size has low porosity and permeability, so it is potential as a cap rock. (author)

  14. Optimising Regionalisation Techniques: Identifying Centres of Endemism in the Extraordinarily Endemic-Rich Cape Floristic Region

    Science.gov (United States)

    Bradshaw, Peter L.; Colville, Jonathan F.; Linder, H. Peter

    2015-01-01

    We used a very large dataset (>40% of all species) from the endemic-rich Cape Floristic Region (CFR) to explore the impact of different weighting techniques, coefficients to calculate similarity among the cells, and clustering approaches on biogeographical regionalisation. The results were used to revise the biogeographical subdivision of the CFR. We show that weighted data (down-weighting widespread species), similarity calculated using Kulczinsky’s second measure, and clustering using UPGMA resulted in the optimal classification. This maximized the number of endemic species, the number of centres recognized, and operational geographic units assigned to centres of endemism (CoEs). We developed a dendrogram branch order cut-off (BOC) method to locate the optimal cut-off points on the dendrogram to define candidate clusters. Kulczinsky’s second measure dendrograms were combined using consensus, identifying areas of conflict which could be due to biotic element overlap or transitional areas. Post-clustering GIS manipulation substantially enhanced the endemic composition and geographic size of candidate CoEs. Although there was broad spatial congruence with previous phytogeographic studies, our techniques allowed for the recovery of additional phytogeographic detail not previously described for the CFR. PMID:26147438

  15. Whole genome population genetics analysis of Sudanese goats identifies regions harboring genes associated with major traits.

    Science.gov (United States)

    Rahmatalla, Siham A; Arends, Danny; Reissmann, Monika; Said Ahmed, Ammar; Wimmers, Klaus; Reyer, Henry; Brockmann, Gudrun A

    2017-10-23

    Sudan is endowed with a variety of indigenous goat breeds which are used for meat and milk production and which are well adapted to the local environment. The aim of the present study was to determine the genetic diversity and relationship within and between the four main Sudanese breeds of Nubian, Desert, Taggar and Nilotic goats. Using the 50 K SNP chip, 24 animals of each breed were genotyped. More than 96% of high quality SNPs were polymorphic with an average minor allele frequency of 0.3. In all breeds, no significant difference between observed (0.4) and expected (0.4) heterozygosity was found and the inbreeding coefficients (F IS ) did not differ from zero. F st coefficients for the genetic distance between breeds also did not significantly deviate from zero. In addition, the analysis of molecular variance revealed that 93% of the total variance in the examined population can be explained by differences among individuals, while only 7% result from differences between the breeds. These findings provide evidence for high genetic diversity and little inbreeding within breeds on one hand, and low diversity between breeds on the other hand. Further examinations using Nei's genetic distance and STRUCTURE analysis clustered Taggar goats distinct from the other breeds. In a principal component (PC) analysis, PC1 could separate Taggar, Nilotic and a mix of Nubian and Desert goats into three groups. The SNPs that contributed strongly to PC1 showed high F st values in Taggar goat versus the other goat breeds. PCA allowed us to identify target genomic regions which contain genes known to influence growth, development, bone formation and the immune system. The information on the genetic variability and diversity in this study confirmed that Taggar goat is genetically different from the other goat breeds in Sudan. The SNPs identified by the first principal components show high F st values in Taggar goat and allowed to identify candidate genes which can be used in the

  16. Regional sensitivity analysis using revised mean and variance ratio functions

    International Nuclear Information System (INIS)

    Wei, Pengfei; Lu, Zhenzhou; Ruan, Wenbin; Song, Jingwen

    2014-01-01

    The variance ratio function, derived from the contribution to sample variance (CSV) plot, is a regional sensitivity index for studying how much the output deviates from the original mean of model output when the distribution range of one input is reduced and to measure the contribution of different distribution ranges of each input to the variance of model output. In this paper, the revised mean and variance ratio functions are developed for quantifying the actual change of the model output mean and variance, respectively, when one reduces the range of one input. The connection between the revised variance ratio function and the original one is derived and discussed. It is shown that compared with the classical variance ratio function, the revised one is more suitable to the evaluation of model output variance due to reduced ranges of model inputs. A Monte Carlo procedure, which needs only a set of samples for implementing it, is developed for efficiently computing the revised mean and variance ratio functions. The revised mean and variance ratio functions are compared with the classical ones by using the Ishigami function. At last, they are applied to a planar 10-bar structure

  17. Defining structural and functional dimensions of the extracellular thyrotropin receptor region.

    Science.gov (United States)

    Kleinau, Gunnar; Mueller, Sandra; Jaeschke, Holger; Grzesik, Paul; Neumann, Susanne; Diehl, Anne; Paschke, Ralf; Krause, Gerd

    2011-06-24

    The extracellular region of the thyrotropin receptor (TSHR) can be subdivided into the leucine-rich repeat domain (LRRD) and the hinge region. Both the LRRD and the hinge region interact with thyrotropin (TSH) or autoantibodies. Structural data for the TSHR LRRD were previously determined by crystallization (amino acids Glu(30)-Thr(257), 10 repeats), but the structure of the hinge region is still undefined. Of note, the amino acid sequence (Trp(258)-Tyr(279)) following the crystallized LRRD comprises a pattern typical for leucine-rich repeats with conserved hydrophobic side chains stabilizing the repeat fold. Moreover, functional data for amino acids between the LRRD and the transmembrane domain were fragmentary. We therefore investigated systematically these TSHR regions by mutagenesis to reveal insights into their functional contribution and potential structural features. We found that mutations of conserved hydrophobic residues between Thr(257) and Tyr(279) cause TSHR misfold, which supports a structural fold of this peptide, probably as an additional leucine-rich repeat. Furthermore, we identified several new mutations of hydrophilic amino acids in the entire hinge region leading to partial TSHR inactivation, indicating that these positions are important for intramolecular signal transduction. In summary, we provide new information regarding the structural features and functionalities of extracellular TSHR regions. Based on these insights and in context with previous results, we suggest an extracellular activation mechanism that supports an intramolecular agonistic unit as a central switch for activating effects at the extracellular region toward the serpentine domain.

  18. Identifying risk factors of avian infectious diseases at household level in Poyang Lake region, China.

    Science.gov (United States)

    Jiang, Qian; Zhou, Jieting; Jiang, Zhiben; Xu, Bing

    2014-09-01

    Poultry kept in backyard farms are susceptible to acquiring and spreading infectious diseases because of free ranging and poor biosecurity measures. Since some of these diseases are zoonoses, this is also a significant health concern to breeders and their families. Backyard farms are common in rural regions of China. However, there is lack of knowledge of backyard poultry in the country. To obtain first-hand information of backyard poultry and identify risk factors of avian infectious diseases, a cross-sectional study was carried out at household level in rural regions around Poyang Lake. A door-to-door survey was conducted to collect data on husbandry practices, trading practices of backyard farmers, and surrounding environments of backyard farms. Farms were categorized into cases and controls based on their history of poultry death. Data were collected for 137 farms, and the association with occurrence of poultry death event was explored by chi-square tests. Results showed that vaccination implementation was a protective factor (odds ratio OR=0.40, 95% confidence interval CI: 0.20-0.80, p=0.01), while contact with other backyard flocks increased risk (OR=1.72, 95% CI: 0.79-3.74, p=0.16). A concept of "farm connectivity" characterized by the density of particular land-use types in the vicinity of the farm was proposed to characterize the degree of contact between poultry in one household farm and those in other household farms. It was found that housing density in a 20-m buffer zone of the farmhouse was most significantly associated with poultry death occurrence (OR=1.08, 95% CI: 1.02-1.17, p=0.03), and was in agreement with observation of villagers. Binary logistic regression was applied to evaluate the relationship between poultry death event and density of land-use types in all buffer zones. When integrated with vaccination implementation for poultry, prediction accuracy of poultry death event reached 72.0%. Results combining questionnaire survey with

  19. Sustaining the grassland sea: Regional perspectives on identifying, protecting and restoring the Sky Island region's most intact grassland valley landscapes

    Science.gov (United States)

    Gitanjali S. Bodner; Peter Warren; David Gori; Karla Sartor; Steven Bassett

    2013-01-01

    Grasslands of the Sky Islands region once covered over 13 million acres in southeastern Arizona and adjacent portions of New Mexico, Sonora, and Chihuahua. Attempts to evaluate current ecological conditions suggest that approximately two thirds of these remain as intact or restorable grassland habitat. These grasslands provide watershed services such as flood control...

  20. Identifying faecal impaction is important for ensuring the timely diagnosis of childhood functional constipation

    DEFF Research Database (Denmark)

    Modin, Line; Walsted, Anne-Mette; Jakobsen, Marianne Skytte

    2015-01-01

    AIM: Most research on functional constipation has been carried out at a tertiary level. We focused this study on a secondary-level hospital outpatients' department, assessing the distribution of diagnostic criteria for childhood functional constipation and evaluating the consequences of current...... diagnostic practice based on current guidelines. METHODS: We enrolled 235 children, aged two to 16 years of age, with functional constipation according to the Rome III criteria and assessed them using medical histories and physical examinations, including rectal examinations and ultrasound measurements...... the timely diagnosis of childhood functional constipation at the secondary care level. Ultrasound examination proved a reliable alternative to rectal examination or abdominal radiography when identifying faecal impaction....

  1. Applicability of Earth Observation for Identifying Small-Scale Mining Footprints in a Wet Tropical Region

    Directory of Open Access Journals (Sweden)

    Celso M. Isidro

    2017-09-01

    Full Text Available The unpredictable climate in wet tropical regions along with the spatial resolution limitations of some satellite imageries make detecting and mapping artisanal and small-scale mining (ASM challenging. The objective of this study was to test the utility of Pleiades and SPOT imagery with an object-based support vector machine (OB-SVM classifier for the multi-temporal remote sensing of ASM and other land cover including a large-scale mine in the Didipio catchment in the Philippines. Historical spatial data on location and type of ASM mines were collected from the field and were utilized as training data for the OB-SVM classifier. The classification had an overall accuracy between 87% and 89% for the three different images—Pleiades-1A for the 2013 and 2014 images and SPOT-6 for the 2016 image. The main land use features, particularly the Didipio large-scale mine, were well identified by the OB-SVM classifier, however there were greater commission errors for the mapping of small-scale mines. The lack of consistency in their shape and their small area relative to pixel sizes meant they were often not distinguished from other land clearance types (i.e., open land. To accurately estimate the total area of each land cover class, we calculated bias-adjusted surface areas based on misclassification values. The analysis showed an increase in small-scale mining areas from 91,000 m2—or 0.2% of the total catchment area—in March 2013 to 121,000 m2—or 0.3%—in May 2014, and then a decrease to 39,000 m2—or 0.1%—in January 2016.

  2. Identifying Opportunities for Decision Support Systems in Support of Regional Resource Use Planning: An Approach Through Soft Systems Methodology.

    Science.gov (United States)

    Zhu; Dale

    2000-10-01

    / Regional resource use planning relies on key regional stakeholder groups using and having equitable access to appropriate social, economic, and environmental information and assessment tools. Decision support systems (DSS) can improve stakeholder access to such information and analysis tools. Regional resource use planning, however, is a complex process involving multiple issues, multiple assessment criteria, multiple stakeholders, and multiple values. There is a need for an approach to DSS development that can assist in understanding and modeling complex problem situations in regional resource use so that areas where DSSs could provide effective support can be identified, and the user requirements can be well established. This paper presents an approach based on the soft systems methodology for identifying DSS opportunities for regional resource use planning, taking the Central Highlands Region of Queensland, Australia, as a case study.

  3. Research in the Functioning of the Regional Budgetary System

    Directory of Open Access Journals (Sweden)

    Mariya Aleksandrovna Pechenskaya

    2015-11-01

    Full Text Available The state regulation conducted in accordance with the current economic policy plays a leading role in the formation and development of the economic structure of modern society. The financial system carries out control activities in the market economy through financial mechanisms by means of financial levers and incentives to achieve financial objectives. Regional public finance, as a major part of the RF financial system, is of great importance for the reproductive process during the transfer to effective market organization of the economy. The state budget is the main link of the financial system. It is an incomparable by its amount monetary fund, winch has huge investment potential and can quantitatively and qualitatively affect the efficiency of social production. The use of this potential to a great extent will determine a development direction and regional economy sustainability. The stability of the budget system is seen in the concept of long term socio-economic development of Russia until 2020 as a vital condition for the solution of strategic economic and social objectives of financial provision of innovative development of the economy. Despite recent reforms, the negative trends persist in the sphere of public finance. The proportion in the distribution of tax revenues between the Federation and its subjects changed from 44–56 in 1997 to 54–46 in 2014 that led to the serious deficit and the debt of regional budgets. The most critical situation is observed in the field of municipal finance. The budgets of even large Russian cities depend on regional subsidies by 25–35%. The regional and district levels were formed during the 2003 local government reform in isolation from the financial-economic base of their functioning. So, as a result, the revenue base of the Vologda Oblast municipal districts decreased by 3.3 times and their transfer dependence from higher levels increased by almost 5 times. About 95% of the settlements in the

  4. Comparative analyses identified species-specific functional roles in oral microbial genomes

    Science.gov (United States)

    Chen, Tsute; Gajare, Prasad; Olsen, Ingar; Dewhirst, Floyd E.

    2017-01-01

    ABSTRACT The advent of next generation sequencing is producing more genomic sequences for various strains of many human oral microbial species and allows for insightful functional comparisons at both intra- and inter-species levels. This study performed in-silico functional comparisons for currently available genomic sequences of major species associated with periodontitis including Aggregatibacter actinomycetemcomitans (AA), Porphyromonas gingivalis (PG), Treponema denticola (TD), and Tannerella forsythia (TF), as well as several cariogenic and commensal streptococcal species. Complete or draft sequences were annotated with the RAST to infer structured functional subsystems for each genome. The subsystems profiles were clustered to groups of functions with similar patterns. Functional enrichment and depletion were evaluated based on hypergeometric distribution to identify subsystems that are unique or missing between two groups of genomes. Unique or missing metabolic pathways and biological functions were identified in different species. For example, components involved in flagellar motility were found only in the motile species TD, as expected, with few exceptions scattered in several streptococcal species, likely associated with chemotaxis. Transposable elements were only found in the two Bacteroidales species PG and TF, and half of the AA genomes. Genes involved in CRISPR were prevalent in most oral species. Furthermore, prophage related subsystems were also commonly found in most species except for PG and Streptococcus mutans, in which very few genomes contain prophage components. Comparisons between pathogenic (P) and nonpathogenic (NP) genomes also identified genes potentially important for virulence. Two such comparisons were performed between AA (P) and several A. aphrophilus (NP) strains, and between S. mutans + S. sobrinus (P) and other oral streptococcal species (NP). This comparative genomics approach can be readily used to identify functions unique to

  5. Receiver Functions of the Mangystau Region, Western Kazakhstan

    Science.gov (United States)

    Martinetti, L. B.; Mackey, K. G.

    2017-12-01

    The Mangystau Region, in southwestern Kazakhstan contains many geographic features such as basins, plateaus, and mountain ranges. However, little has been published in English or Russian, and the region has never been instrumented with broadband seismometers before. From August through September 2016, a seismic noise survey took place where 10 broadband seismic stations were deployed throughout the region for 20 days each by MSU. The sensors recorded various teleseismic events and the data were used to infer crustal thickness. The goal of this study is to determine if reliable receiver functions can be created with 20 days of data recorded, and test what is the best way to use the data to find the thickness of the crust. Since a limited amount of data is available, teleseismic events of magnitude > 5 and that occurred from 30 to 90 degrees from the station were used. To have a better solution, a local calibration event was used to solve the seismic velocity and match the results of a previously done study (5.6 - 6.5 km/s) by a Kazak group, which was then used for H-k stacking. While the work is still in progress, it will add to the knowledge of the area, thus give an insight to the crustal thickness of the overall region. This study can also be used to provide information of the crustal thickness of the northern Caspian basin, near the Caucasus, where another major effort is being conducted.

  6. Identifying functional zones of denitrification in heterogeneous aquifer systems by numerical simulations - a case study

    Science.gov (United States)

    Jang, E.; Kalbacher, T.; He, W.; Shao, H.; Schueth, C.; Kolditz, O.

    2014-12-01

    Nitrate contamination in shallow groundwater is still one of the common problems in many countries. Because of its high solubility and anionic nature, nitrate can easily leach through soil and persist in groundwater for decades. High nitrate concentration has been suggested as a major cause of accelerated eutrophication, methemoglobinemia and gastric cancer. There are several factors influencing the fate of nitrate in groundwater system, which is e.g. distribution of N- sources to soil and groundwater, distribution and amount of reactive substances maintaining denitrification, rate of nitrate degradation and its kinetics, and geological characteristics of the aquifer. Nitrate transport and redox transformation processes are closely linked to complex and spatially distributed physical and chemical interaction, therefore it is difficult to predict and quantify in the field and laboratory experiment. Models can play a key role in elucidation of nitrate reduction pathway in groundwater system and in the design and evaluation of field tests to investigate in situ remediation technologies as well. The goal of the current study is to predict groundwater vulnerability to nitrate, to identify functional zones of denitrification in heterogeneous aquifer systems and to describe the uncertainty of the predictions due to scale effects. For this aim, we developed a kinetic model using multi-component mass transport code OpenGeoSys coupling with IPhreeqc module of the geochemical solver PHREEQC. The developed model included sequential aerobic and nitrate-based respiration, multi-Monod kinetics, multi-species biogeochemical reactions, and geological characteristics of the groundwater aquifer. Moreover water-rock interaction such as secondary mineral precipitation was also included in this model. In this presentation, we focused on the general modelling approach and present the simulation results of nitrate transport simulation in a hypothetical aquifer systems based on data from

  7. Operational flood forecasting system of Umbria Region "Functional Centre

    Science.gov (United States)

    Berni, N.; Pandolfo, C.; Stelluti, M.; Ponziani, F.; Viterbo, A.

    2009-04-01

    The hydrometeorological alert office (called "Decentrate Functional Centre" - CFD) of Umbria Region, in central Italy, is the office that provides technical tools able to support decisions when significant flood/landslide events occur, furnishing 24h support for the whole duration of the emergency period, according to the national directive DPCM 27 February 2004 concerning the "Operating concepts for functional management of national and regional alert system during flooding and landslide events for civil protection activities purposes" that designs, within the Italian Civil Defence Emergency Management System, a network of 21 regional Functional Centres coordinated by a central office at the National Civil Protection Department in Rome. Due to its "linking" role between Civil Protection "real time" activities and environmental/planning "deferred time" ones, the Centre is in charge to acquire and collect both real time and quasi-static data: quantitative data from monitoring networks (hydrometeorological stations, meteo radar, ...), meteorological forecasting models output, Earth Observation data, hydraulic and hydrological simulation models, cartographic and thematic GIS data (vectorial and raster type), planning studies related to flooding areas mapping, dam managing plans during flood events, non instrumental information from direct control of "territorial presidium". A detailed procedure for the management of critical events was planned, also in order to define the different role of various authorities and institutions involved. Tiber River catchment, of which Umbria region represents the main upper-medium portion, includes also regional trans-boundary issues very important to cope with, especially for what concerns large dam behavior and management during heavy rainfall. The alert system is referred to 6 different warning areas in which the territory has been divided into and based on a threshold system of three different increasing critical levels according

  8. Orofacial complex regional pain syndrome: pathophysiologic mechanisms and functional MRI.

    Science.gov (United States)

    Lee, Yeon-Hee; Lee, Kyung Mi; Kim, Hyug-Gi; Kang, Soo-Kyung; Auh, Q-Schick; Hong, Jyung-Pyo; Chun, Yang-Hyun

    2017-08-01

    Complex regional pain syndrome (CRPS) is one of the most challenging chronic pain conditions and is characterized by burning pain, allodynia, hyperalgesia, autonomic changes, trophic changes, edema, and functional loss involving mainly the extremities. Until recently, very few reports have been published concerning CRPS involving the orofacial area. We report on a 50-year-old female patient who presented with unbearable pain in all of her teeth and hypersensitivity of the facial skin. She also reported intractable pain in both extremities accompanied by temperature changes and orofacial pain that increased when the other pains were aggravated. In the case of CRPS with trigeminal neuropathic pain, protocols for proper diagnosis and prompt treatment have yet to be established in academia or in the clinical field. We performed functional magnetic resonance imaging for a thorough analysis of the cortical representation of the affected orofacial area immediately before and immediately after isolated light stimulus of the affected hand and foot and concluded that CRPS can be correlated with trigeminal neuropathy in the orofacial area. Furthermore, the patient was treated with carbamazepine administration and stellate ganglion block, which can result in a rapid improvement of pain in the trigeminal region. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Identifying classes of persons with mild intellectual disability or borderline intellectual functioning : A latent class analysis

    NARCIS (Netherlands)

    Nouwens, P.J.G.; Lucas, R.; Smulders, N.B.M.; Embregts, P.J.C.M.; van Nieuwenhuizen, Ch.

    2017-01-01

    Background Persons with mild intellectual disability or borderline intellectual functioning are often studied as a single group with similar characteristics. However, there are indications that differences exist within this population. Therefore, the aim of this study was to identify classes of

  10. Identifying support functions in developmental relationships: A self-determination perspective

    NARCIS (Netherlands)

    Janssen, Suzanne; van Vuuren, Hubrecht A.; de Jong, Menno D.T.

    2013-01-01

    This study examines the content of developmental networks from the perspective of self-determination theory. We qualitatively examine 18 protégés' constellations of developmental relationships to identify specific types of developmental support functions. Our study shows that the adoption of

  11. Semantic integration to identify overlapping functional modules in protein interaction networks

    Directory of Open Access Journals (Sweden)

    Ramanathan Murali

    2007-07-01

    Full Text Available Abstract Background The systematic analysis of protein-protein interactions can enable a better understanding of cellular organization, processes and functions. Functional modules can be identified from the protein interaction networks derived from experimental data sets. However, these analyses are challenging because of the presence of unreliable interactions and the complex connectivity of the network. The integration of protein-protein interactions with the data from other sources can be leveraged for improving the effectiveness of functional module detection algorithms. Results We have developed novel metrics, called semantic similarity and semantic interactivity, which use Gene Ontology (GO annotations to measure the reliability of protein-protein interactions. The protein interaction networks can be converted into a weighted graph representation by assigning the reliability values to each interaction as a weight. We presented a flow-based modularization algorithm to efficiently identify overlapping modules in the weighted interaction networks. The experimental results show that the semantic similarity and semantic interactivity of interacting pairs were positively correlated with functional co-occurrence. The effectiveness of the algorithm for identifying modules was evaluated using functional categories from the MIPS database. We demonstrated that our algorithm had higher accuracy compared to other competing approaches. Conclusion The integration of protein interaction networks with GO annotation data and the capability of detecting overlapping modules substantially improve the accuracy of module identification.

  12. Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region

    NARCIS (Netherlands)

    Skibola, Christine F.; Berndt, Sonja I.; Vijai, Joseph; Conde, Lucia; Wang, Zhaoming; Yeager, Meredith; de Bakker, Paul I. W.; Birmann, Brenda M.; Vajdic, Claire M.; Foo, Jia-Nee; Bracci, Paige M.; Vermeulen, Roel C. H.; Slager, Susan L.; de Sanjose, Silvia; Wang, Sophia S.; Linet, Martha S.; Salles, Gilles; Lan, Qing; Severi, Gianluca; Hjalgrim, Henrik; Lightfoot, Tracy; Melbye, Mads; Gu, Jian; Ghesquieres, Herve; Link, Brian K.; Morton, Lindsay M.; Holly, Elizabeth A.; Smith, Alex; Tinker, Lesley F.; Teras, Lauren R.; Kricker, Anne; Becker, Nikolaus; Purdue, Mark P.; Spinelli, John J.; Zhang, Yawei; Giles, Graham G.; Vineis, Paolo; Monnereau, Alain; Bertrand, Kimberly A.; Albanes, Demetrius; Zeleniuch-Jacquotte, Anne; Gabbas, Attilio; Chung, Charles C.; Burdett, Laurie; Hutchinson, Amy; Lawrence, Charles; Montalvan, Rebecca; Liang, Liming; Huang, Jinyan; Ma, Baoshan; Liu, Jianjun; Adami, Hans-Olov; Glimelius, Bengt; Ye, Yuanqing; Nowakowski, Grzegorz S.; Dogan, Ahmet; Thompson, Carrie A.; Habermann, Thomas M.; Novak, Anne J.; Liebow, Mark; Witzig, Thomas E.; Weiner, George J.; Schenk, Maryjean; Hartge, Patricia; De Roos, Anneclaire J.; Cozen, Wendy; Zhi, Degui; Akers, Nicholas K.; Riby, Jacques; Smith, Martyn T.; Lacher, Mortimer; Villano, Danylo J.; Maria, Ann; Roman, Eve; Kane, Eleanor; Jackson, Rebecca D.; North, Kari E.; Diver, W. Ryan; Turner, Jenny; Armstrong, Bruce K.; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; McKay, James; Brooks-Wilson, Angela R.; Zheng, Tongzhang; Holford, Theodore R.; Chamosa, Saioa; Kaaks, Rudolph; Kelly, Rachel S.; Ohlsson, Bodil; Travis, Ruth C.; Weiderpass, Elisabete; Clave, Jacqueline; Giovannucci, Edward; Kraft, Peter; Virtamo, Jarmo; Mazza, Patrizio; Cocco, Pierluigi; Ennas, Maria Grazia; Chiu, Brian C. H.; Fraumeni, Joseph R.; Nieters, Alexandra; Offit, Kenneth; Wu, Xifeng; Cerhan, James R.; Smedby, Karin E.; Chanock, Stephen J.; Rothman, Nathaniel

    2014-01-01

    Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European

  13. Quantitative expression profile of distinct functional regions in the adult mouse brain.

    Directory of Open Access Journals (Sweden)

    Takeya Kasukawa

    Full Text Available The adult mammalian brain is composed of distinct regions with specialized roles including regulation of circadian clocks, feeding, sleep/awake, and seasonal rhythms. To find quantitative differences of expression among such various brain regions, we conducted the BrainStars (B* project, in which we profiled the genome-wide expression of ∼50 small brain regions, including sensory centers, and centers for motion, time, memory, fear, and feeding. To avoid confounds from temporal differences in gene expression, we sampled each region every 4 hours for 24 hours, and pooled the samples for DNA-microarray assays. Therefore, we focused on spatial differences in gene expression. We used informatics to identify candidate genes with expression changes showing high or low expression in specific regions. We also identified candidate genes with stable expression across brain regions that can be used as new internal control genes, and ligand-receptor interactions of neurohormones and neurotransmitters. Through these analyses, we found 8,159 multi-state genes, 2,212 regional marker gene candidates for 44 small brain regions, 915 internal control gene candidates, and 23,864 inferred ligand-receptor interactions. We also found that these sets include well-known genes as well as novel candidate genes that might be related to specific functions in brain regions. We used our findings to develop an integrated database (http://brainstars.org/ for exploring genome-wide expression in the adult mouse brain, and have made this database openly accessible. These new resources will help accelerate the functional analysis of the mammalian brain and the elucidation of its regulatory network systems.

  14. Multiple-region directed functional connectivity based on phase delays.

    Science.gov (United States)

    Goelman, Gadi; Dan, Rotem

    2017-03-01

    Network analysis is increasingly advancing the field of neuroimaging. Neural networks are generally constructed from pairwise interactions with an assumption of linear relations between them. Here, a high-order statistical framework to calculate directed functional connectivity among multiple regions, using wavelet analysis and spectral coherence has been presented. The mathematical expression for 4 regions was derived and used to characterize a quartet of regions as a linear, combined (nonlinear), or disconnected network. Phase delays between regions were used to obtain network's temporal hierarchy and directionality. The validity of the mathematical derivation along with the effects of coupling strength and noise on its outcomes were studied by computer simulations of the Kuramoto model. The simulations demonstrated correct directionality for a large range of coupling strength and low sensitivity to Gaussian noise compared with pairwise coherences. The analysis was applied to resting-state fMRI data of 40 healthy young subjects to characterize the ventral visual system, motor system and default mode network (DMN). It was shown that the ventral visual system was predominantly composed of linear networks while the motor system and the DMN were composed of combined (nonlinear) networks. The ventral visual system exhibits its known temporal hierarchy, the motor system exhibits center ↔ out hierarchy and the DMN has dorsal ↔ ventral and anterior ↔ posterior organizations. The analysis can be applied in different disciplines such as seismology, or economy and in a variety of brain data including stimulus-driven fMRI, electrophysiology, EEG, and MEG, thus open new horizons in brain research. Hum Brain Mapp 38:1374-1386, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Benefits of coastal recreation in Europe: identifying trade-offs and priority regions for sustainable management.

    Science.gov (United States)

    Ghermandi, Andrea

    2015-04-01

    This paper examines the welfare dimension of the recreational services of coastal ecosystems through the application of a meta-analytical value transfer framework, which integrates Geographic Information Systems (GIS) for the characterization of climate, biodiversity, accessibility, and anthropogenic pressure in each of 368 regions of the European coastal zone. The relative contribution of international, domestic, and local recreationists to aggregated regional values is examined. The implications of the analysis for prioritization of conservation areas and identification of good management practices are highlighted through the comparative assessment of estimated recreation values, current environmental pressures, and existing network of protected sites. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Indicators of ecosystem function identify alternate states in the sagebrush steppe.

    Science.gov (United States)

    Kachergis, Emily; Rocca, Monique E; Fernandez-Gimenez, Maria E

    2011-10-01

    Models of ecosystem change that incorporate nonlinear dynamics and thresholds, such as state-and-transition models (STMs), are increasingly popular tools for land management decision-making. However, few models are based on systematic collection and documentation of ecological data, and of these, most rely solely on structural indicators (species composition) to identify states and transitions. As STMs are adopted as an assessment framework throughout the United States, finding effective and efficient ways to create data-driven models that integrate ecosystem function and structure is vital. This study aims to (1) evaluate the utility of functional indicators (indicators of rangeland health, IRH) as proxies for more difficult ecosystem function measurements and (2) create a data-driven STM for the sagebrush steppe of Colorado, USA, that incorporates both ecosystem structure and function. We sampled soils, plant communities, and IRH at 41 plots with similar clayey soils but different site histories to identify potential states and infer the effects of management practices and disturbances on transitions. We found that many IRH were correlated with quantitative measures of functional indicators, suggesting that the IRH can be used to approximate ecosystem function. In addition to a reference state that functions as expected for this soil type, we identified four biotically and functionally distinct potential states, consistent with the theoretical concept of alternate states. Three potential states were related to management practices (chemical and mechanical shrub treatments and seeding history) while one was related only to ecosystem processes (erosion). IRH and potential states were also related to environmental variation (slope, soil texture), suggesting that there are environmental factors within areas with similar soils that affect ecosystem dynamics and should be noted within STMs. Our approach generated an objective, data-driven model of ecosystem dynamics

  17. Functional and effective whole brain connectivity using magnetoencephalography to identify monozygotic twin pairs.

    Science.gov (United States)

    Demuru, M; Gouw, A A; Hillebrand, A; Stam, C J; van Dijk, B W; Scheltens, P; Tijms, B M; Konijnenberg, E; Ten Kate, M; den Braber, A; Smit, D J A; Boomsma, D I; Visser, P J

    2017-08-29

    Resting-state functional connectivity patterns are highly stable over time within subjects. This suggests that such 'functional fingerprints' may have strong genetic component. We investigated whether the functional (FC) or effective (EC) connectivity patterns of one monozygotic twin could be used to identify the co-twin among a larger sample and determined the overlap in functional fingerprints within monozygotic (MZ) twin pairs using resting state magnetoencephalography (MEG). We included 32 cognitively normal MZ twin pairs from the Netherlands Twin Register who participate in the EMIF-AD preclinAD study (average age 68 years). Combining EC information across multiple frequency bands we obtained an identification rate over 75%. Since MZ twin pairs are genetically identical these results suggest a high genetic contribution to MEG-based EC patterns, leading to large similarities in brain connectivity patterns between two individuals even after 60 years of life or more.

  18. Identifying classes of persons with mild intellectual disability or borderline intellectual functioning: a latent class analysis.

    Science.gov (United States)

    Nouwens, Peter J G; Lucas, Rosanne; Smulders, Nienke B M; Embregts, Petri J C M; van Nieuwenhuizen, Chijs

    2017-07-17

    Persons with mild intellectual disability or borderline intellectual functioning are often studied as a single group with similar characteristics. However, there are indications that differences exist within this population. Therefore, the aim of this study was to identify classes of persons with mild intellectual disability or borderline intellectual functioning and to examine whether these classes are related to individual and/or environmental characteristics. Latent class analysis was performed using file data of 250 eligible participants with a mean age of 26.1 (SD 13.8, range 3-70) years. Five distinct classes of persons with mild intellectual disability or borderline intellectual functioning were found. These classes significantly differed in individual and environmental characteristics. For example, persons with a mild intellectual disability experienced fewer problems than those with borderline intellectual disability. The identification of five classes implies that a differentiated approach is required towards persons with mild intellectual disability or borderline intellectual functioning.

  19. Liver Function Indicators Performed Better to Eliminate Cardioembolic Stroke than to Identify It from Stroke Subtypes.

    Science.gov (United States)

    Tan, Ge; Yuan, Ruozhen; Hao, Zilong; Lei, Chunyan; Xiong, Yao; Xu, Mangmang; Liu, Ming

    2017-01-01

    Identifying the etiology of ischemic stroke is essential to acute management and secondary prevention. The value of liver function indicators in differentiating stroke subtypes remains to be evaluated. A total of 1333 acute ischemic stroke patients were included. Liver function indicators collected within 24 hours from stroke onset, including alanine aminotransferase, aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), and bilirubin (BILI), were collapsed into quartiles (Q) and also dichotomized by Q1. Multivariate regression analysis was conducted to identify the independent association between liver function indicators and cardioembolic stroke (SCE). Area under the curve (AUC) of receiver operating characteristic analysis was conducted, and sensitivity (Sen), specificity (Spe), positive prospective value (PPV), and negative prospective value (NPV) were determined to evaluate the predictive value of liver function indicators for SCE. AST, GGT, and BILI were associated with SCE. After adjustment, only AST was related to SCE independently. The incidence of SCE in the Q1 of AST, GGT, and BILI, particularly in the Q1 of AST, was quite low. The ability of AST, GGT, and BILI to identify SCE was poor, with low AUC, Sen, and PPV. The value of AST, GGT, and BILI in eliminating SCE from stroke subtypes was good, with high Spe and moderate NPV, and was enhanced after combining each liver function indicator. Results of present study demonstrated that AST, GGT, and BILI, particularly AST, had a potential to eliminate SCE from stroke subtypes, and the ability of eliminating SCE would be strengthened after combining each liver function indicator together. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  20. Aging, regional cerebral blood flow, and neuropsychological functioning

    International Nuclear Information System (INIS)

    MacInnes, W.D.; Golden, C.J.; Gillen, R.W.; Sawicki, R.F.; Quaife, M.; Uhl, H.S.; Greenhouse, A.J.

    1984-01-01

    Previous studies found changes in regional cerebral blood flow (rCBF) patterns related to both age and various cognitive tasks. However, no study has yet demonstrated a relationship between rCBF and performance on the Luria-Nebraska Neuropsychological Battery (LNNB) in an elderly group. Seventy-nine elderly volunteers (56-88 years old), both healthy and demented, underwent the 133 xenon inhalation rCBF procedure and were given the LNNB. The decrements in the gray-matter blood flow paralleled decrements in performance on the LNNB. Using partial correlations, a significant proportion of shared variance was observed between gray-matter blood flow and the LNNB scales. However, there was much less of a relationship between white-matter blood flow and performance on the LNNB. This study suggests that even within a restricted age sample rCBF is related in a global way to neuropsychological functioning

  1. Utility and Limitations of Using Gene Expression Data to Identify Functional Associations.

    Directory of Open Access Journals (Sweden)

    Sahra Uygun

    2016-12-01

    Full Text Available Gene co-expression has been widely used to hypothesize gene function through guilt-by association. However, it is not clear to what degree co-expression is informative, whether it can be applied to genes involved in different biological processes, and how the type of dataset impacts inferences about gene functions. Here our goal is to assess the utility and limitations of using co-expression as a criterion to recover functional associations between genes. By determining the percentage of gene pairs in a metabolic pathway with significant expression correlation, we found that many genes in the same pathway do not have similar transcript profiles and the choice of dataset, annotation quality, gene function, expression similarity measure, and clustering approach significantly impacts the ability to recover functional associations between genes using Arabidopsis thaliana as an example. Some datasets are more informative in capturing coordinated expression profiles and larger data sets are not always better. In addition, to recover the maximum number of known pathways and identify candidate genes with similar functions, it is important to explore rather exhaustively multiple dataset combinations, similarity measures, clustering algorithms and parameters. Finally, we validated the biological relevance of co-expression cluster memberships with an independent phenomics dataset and found that genes that consistently cluster with leucine degradation genes tend to have similar leucine levels in mutants. This study provides a framework for obtaining gene functional associations by maximizing the information that can be obtained from gene expression datasets.

  2. Systematic Functional Interrogation of Rare Cancer Variants Identifies Oncogenic Alleles | Office of Cancer Genomics

    Science.gov (United States)

    Cancer genome characterization efforts now provide an initial view of the somatic alterations in primary tumors. However, most point mutations occur at low frequency, and the function of these alleles remains undefined. We have developed a scalable systematic approach to interrogate the function of cancer-associated gene variants. We subjected 474 mutant alleles curated from 5,338 tumors to pooled in vivo tumor formation assays and gene expression profiling. We identified 12 transforming alleles, including two in genes (PIK3CB, POT1) that have not been shown to be tumorigenic.

  3. Do protostellar fountains shape the regional core mass function?

    International Nuclear Information System (INIS)

    Li Jin-Zeng; Huang Ya-Fang; Carlos Mallamaci Claudio; César Podestà Ricardo; Actis Vicente Eloy; Maria Pacheco Ana

    2013-01-01

    The emerging massive binary system associated with AFGL 961 signifies the latest generation of massive star and cluster formation in the Rosette Molecular Complex. We present the detection of a compact cluster of dusty cores toward the AFGL 961 region based on continuum imaging at 1.3 mm by the Submillimeter Array. The binary components of AFGL 961 are associated with the most intensive millimeter emission cores or envelopes, confirming that they are indeed in an early stage of evolution. The other massive cores, however, are found to congregate in the close vicinity of the central high-mass protostellar binary. They have no apparent infrared counterparts and are, in particular, well aligned transverse to the bipolar molecular outflows originating from AFGL 961. This provides evidence for a likely triggered origin of the massive cores. All 40 individual cores with masses ranging between 0.6 and 15 Msun were detected above a 3 σ level of 3.6 mJy beam −1 (or 0.4 Msun), based on which we derive a total core mass of 107 Msun in the AFGL 961 region. As compared to the stellar initial mass function, a shallow slope of 1.8 is, however, derived from the best fit to the mass spectrum of the millimeter cores with a prestellar and/or protostellar origin. The flatter core mass distribution in the AFGL 961 region is attributed here to dynamic perturbations from the massive molecular outflows that originated from the massive protostellar binary, which may have altered the otherwise more quiescent conditions of core or star formation, enhanced the formation of more massive cores and, as a result, influenced the core mass distribution in its close vicinity.

  4. Very high resolution regional climate model simulations over Greenland: Identifying added value

    DEFF Research Database (Denmark)

    Lucas-Picher, P.; Wulff-Nielsen, M.; Christensen, J.H.

    2012-01-01

    models. However, the bias between the simulations and the few available observations does not reduce with higher resolution. This is partly explained by the lack of observations in regions where the higher resolution is expected to improve the simulated climate. The RCM simulations show......This study presents two simulations of the climate over Greenland with the regional climate model (RCM) HIRHAM5 at 0.05° and 0.25° resolution driven at the lateral boundaries by the ERA-Interim reanalysis for the period 1989–2009. These simulations are validated against observations from...... that the temperature has increased the most in the northern part of Greenland and at lower elevations over the period 1989–2009. Higher resolution increases the relief variability in the model topography and causes the simulated precipitation to be larger on the coast and smaller over the main ice sheet compared...

  5. Genes Important for Schizosaccharomyces pombe Meiosis Identified Through a Functional Genomics Screen

    Science.gov (United States)

    Blyth, Julie; Makrantoni, Vasso; Barton, Rachael E.; Spanos, Christos; Rappsilber, Juri; Marston, Adele L.

    2018-01-01

    Meiosis is a specialized cell division that generates gametes, such as eggs and sperm. Errors in meiosis result in miscarriages and are the leading cause of birth defects; however, the molecular origins of these defects remain unknown. Studies in model organisms are beginning to identify the genes and pathways important for meiosis, but the parts list is still poorly defined. Here we present a comprehensive catalog of genes important for meiosis in the fission yeast, Schizosaccharomyces pombe. Our genome-wide functional screen surveyed all nonessential genes for roles in chromosome segregation and spore formation. Novel genes important at distinct stages of the meiotic chromosome segregation and differentiation program were identified. Preliminary characterization implicated three of these genes in centrosome/spindle pole body, centromere, and cohesion function. Our findings represent a near-complete parts list of genes important for meiosis in fission yeast, providing a valuable resource to advance our molecular understanding of meiosis. PMID:29259000

  6. Protein functional links in Trypanosoma brucei, identified by gene fusion analysis

    Directory of Open Access Journals (Sweden)

    Trimpalis Philip

    2011-07-01

    Full Text Available Abstract Background Domain or gene fusion analysis is a bioinformatics method for detecting gene fusions in one organism by comparing its genome to that of other organisms. The occurrence of gene fusions suggests that the two original genes that participated in the fusion are functionally linked, i.e. their gene products interact either as part of a multi-subunit protein complex, or in a metabolic pathway. Gene fusion analysis has been used to identify protein functional links in prokaryotes as well as in eukaryotic model organisms, such as yeast and Drosophila. Results In this study we have extended this approach to include a number of recently sequenced protists, four of which are pathogenic, to identify fusion linked proteins in Trypanosoma brucei, the causative agent of African sleeping sickness. We have also examined the evolution of the gene fusion events identified, to determine whether they can be attributed to fusion or fission, by looking at the conservation of the fused genes and of the individual component genes across the major eukaryotic and prokaryotic lineages. We find relatively limited occurrence of gene fusions/fissions within the protist lineages examined. Our results point to two trypanosome-specific gene fissions, which have recently been experimentally confirmed, one fusion involving proteins involved in the same metabolic pathway, as well as two novel putative functional links between fusion-linked protein pairs. Conclusions This is the first study of protein functional links in T. brucei identified by gene fusion analysis. We have used strict thresholds and only discuss results which are highly likely to be genuine and which either have already been or can be experimentally verified. We discuss the possible impact of the identification of these novel putative protein-protein interactions, to the development of new trypanosome therapeutic drugs.

  7. A genome-wide association scan in pig identifies novel regions associated with feed efficiency trait

    DEFF Research Database (Denmark)

    Sahana, Goutam; Kadlecová, Veronika; Hornshøj, Henrik

    2013-01-01

    Feed conversion ratio (FCR) is an economically important trait in pigs and feed accounts for a significant proportion of the costs involved in pig production. In this study we used a high density SNP chip panel, Porcine SNP60 BeadChip, to identify association between FCR and SNP markers and to st...

  8. Functional genomics identifies regulators of the phototransduction machinery in the Drosophila larval eye and adult ocelli.

    Science.gov (United States)

    Mishra, Abhishek Kumar; Bargmann, Bastiaan O R; Tsachaki, Maria; Fritsch, Cornelia; Sprecher, Simon G

    2016-02-15

    Sensory perception of light is mediated by specialized Photoreceptor neurons (PRs) in the eye. During development all PRs are genetically determined to express a specific Rhodopsin (Rh) gene and genes mediating a functional phototransduction pathway. While the genetic and molecular mechanisms of PR development is well described in the adult compound eye, it remains unclear how the expression of Rhodopsins and the phototransduction cascade is regulated in other visual organs in Drosophila, such as the larval eye and adult ocelli. Using transcriptome analysis of larval PR-subtypes and ocellar PRs we identify and study new regulators required during PR differentiation or necessary for the expression of specific signaling molecules of the functional phototransduction pathway. We found that the transcription factor Krüppel (Kr) is enriched in the larval eye and controls PR differentiation by promoting Rh5 and Rh6 expression. We also identified Camta, Lola, Dve and Hazy as key genes acting during ocellar PR differentiation. Further we show that these transcriptional regulators control gene expression of the phototransduction cascade in both larval eye and adult ocelli. Our results show that PR cell type-specific transcriptome profiling is a powerful tool to identify key transcriptional regulators involved during several aspects of PR development and differentiation. Our findings greatly contribute to the understanding of how combinatorial action of key transcriptional regulators control PR development and the regulation of a functional phototransduction pathway in both larval eye and adult ocelli. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Identifying thematic roles from neural representations measured by functional magnetic resonance imaging.

    Science.gov (United States)

    Wang, Jing; Cherkassky, Vladimir L; Yang, Ying; Chang, Kai-Min Kevin; Vargas, Robert; Diana, Nicholas; Just, Marcel Adam

    2016-01-01

    The generativity and complexity of human thought stem in large part from the ability to represent relations among concepts and form propositions. The current study reveals how a given object such as rabbit is neurally encoded differently and identifiably depending on whether it is an agent ("the rabbit punches the monkey") or a patient ("the monkey punches the rabbit"). Machine-learning classifiers were trained on functional magnetic resonance imaging (fMRI) data evoked by a set of short videos that conveyed agent-verb-patient propositions. When tested on a held-out video, the classifiers were able to reliably identify the thematic role of an object from its associated fMRI activation pattern. Moreover, when trained on one subset of the study participants, classifiers reliably identified the thematic roles in the data of a left-out participant (mean accuracy = .66), indicating that the neural representations of thematic roles were common across individuals.

  10. A human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs.

    Science.gov (United States)

    Karlas, Alexander; Berre, Stefano; Couderc, Thérèse; Varjak, Margus; Braun, Peter; Meyer, Michael; Gangneux, Nicolas; Karo-Astover, Liis; Weege, Friderike; Raftery, Martin; Schönrich, Günther; Klemm, Uwe; Wurzlbauer, Anne; Bracher, Franz; Merits, Andres; Meyer, Thomas F; Lecuit, Marc

    2016-05-12

    Chikungunya virus (CHIKV) is a globally spreading alphavirus against which there is no commercially available vaccine or therapy. Here we use a genome-wide siRNA screen to identify 156 proviral and 41 antiviral host factors affecting CHIKV replication. We analyse the cellular pathways in which human proviral genes are involved and identify druggable targets. Twenty-one small-molecule inhibitors, some of which are FDA approved, targeting six proviral factors or pathways, have high antiviral activity in vitro, with low toxicity. Three identified inhibitors have prophylactic antiviral effects in mouse models of chikungunya infection. Two of them, the calmodulin inhibitor pimozide and the fatty acid synthesis inhibitor TOFA, have a therapeutic effect in vivo when combined. These results demonstrate the value of loss-of-function screening and pathway analysis for the rational identification of small molecules with therapeutic potential and pave the way for the development of new, host-directed, antiviral agents.

  11. The systematic functional analysis of plasmodium protein kinases identifies essential regulators of mosquito transmission

    KAUST Repository

    Tewari, Rita; Straschil, Ursula; Bateman, Alex; Bö hme, Ulrike; Cherevach, Inna; Gong, Peng; Pain, Arnab; Billker, Oliver

    2010-01-01

    Although eukaryotic protein kinases (ePKs) contribute to many cellular processes, only three Plasmodium falciparum ePKs have thus far been identified as essential for parasite asexual blood stage development. To identify pathways essential for parasite transmission between their mammalian host and mosquito vector, we undertook a systematic functional analysis of ePKs in the genetically tractable rodent parasite Plasmodium berghei. Modeling domain signatures of conventional ePKs identified 66 putative Plasmodium ePKs. Kinomes are highly conserved between Plasmodium species. Using reverse genetics, we show that 23 ePKs are redundant for asexual erythrocytic parasite development in mice. Phenotyping mutants at four life cycle stages in Anopheles stephensi mosquitoes revealed functional clusters of kinases required for sexual development and sporogony. Roles for a putative SR protein kinase (SRPK) in microgamete formation, a conserved regulator of clathrin uncoating (GAK) in ookinete formation, and a likely regulator of energy metabolism (SNF1/KIN) in sporozoite development were identified. 2010 Elsevier Inc.

  12. The systematic functional analysis of plasmodium protein kinases identifies essential regulators of mosquito transmission

    KAUST Repository

    Tewari, Rita

    2010-10-21

    Although eukaryotic protein kinases (ePKs) contribute to many cellular processes, only three Plasmodium falciparum ePKs have thus far been identified as essential for parasite asexual blood stage development. To identify pathways essential for parasite transmission between their mammalian host and mosquito vector, we undertook a systematic functional analysis of ePKs in the genetically tractable rodent parasite Plasmodium berghei. Modeling domain signatures of conventional ePKs identified 66 putative Plasmodium ePKs. Kinomes are highly conserved between Plasmodium species. Using reverse genetics, we show that 23 ePKs are redundant for asexual erythrocytic parasite development in mice. Phenotyping mutants at four life cycle stages in Anopheles stephensi mosquitoes revealed functional clusters of kinases required for sexual development and sporogony. Roles for a putative SR protein kinase (SRPK) in microgamete formation, a conserved regulator of clathrin uncoating (GAK) in ookinete formation, and a likely regulator of energy metabolism (SNF1/KIN) in sporozoite development were identified. 2010 Elsevier Inc.

  13. Identifying Isotropic Events using an Improved Regional Moment Tensor Inversion Technique

    Energy Technology Data Exchange (ETDEWEB)

    Dreger, Douglas S. [Univ. of California, Berkeley, CA (United States); Ford, Sean R. [Univ. of California, Berkeley, CA (United States); Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Walter, William R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-12-08

    Research was carried out investigating the feasibility of using a regional distance seismic waveform moment tensor inverse procedure to estimate source parameters of nuclear explosions and to use the source inversion results to develop a source-type discrimination capability. The results of the research indicate that it is possible to robustly determine the seismic moment tensor of nuclear explosions, and when compared to natural seismicity in the context of the a Hudson et al. (1989) source-type diagram they are found to separate from populations of earthquakes and underground cavity collapse seismic sources.

  14. Identifying Causes of Construction Waste – Case of Central Region of Peninsula Malaysia

    OpenAIRE

    Sasitharan Nagapan; Ismail Abdul Rahman; Ade Asmi; Aftab Hameed Memon; Rosli Mohammad Zin

    2012-01-01

    Construction waste becomes a global issue facing by practitioners and researchers around the world. Waste can affects success of construction project significantly. More specifically, it has major impact on construction cost, construction time, productivity and sustainability aspects. This paper aims to identify various factors causing construction waste in Malaysia. Study was carried out through structured questionnaire focusing three major parties (i.e. clients, consultants and contractors)...

  15. Identifying the adaptive mechanism in globular proteins: Fluctuations in densely packed regions manipulate flexible parts

    Science.gov (United States)

    Yilmaz, Lutfu Safak; Atilgan, Ali Rana

    2000-09-01

    A low-resolution structural model based on the packing geometry of α-carbons is utilized to establish a connection between the flexible and rigid parts of a folded protein. The former commonly recognizes a complementing molecule for making a complex, while the latter manipulates the necessary conformational change for binding. We attempt analytically to distinguish this control architecture that intrinsically exists in globular proteins. First with two-dimensional simple models, then for a native protein, bovine pancreatic trypsin inhibitor, we explicitly demonstrate that inserting fluctuations in tertiary contacts supported by the stable core, one can regulate the displacement of residues on loop regions. The positional fluctuations of the flexible regions are annihilated by the rest of the protein in conformity with the Le Chatelier-Braun principle. The results indicate that the distortion of the principal nonbonded contacts between highly packed residues is accompanied by that of the slavery fluctuations that are widely distributed over the native structure. These positional arrangements do not appear in a reciprocal relation between a perturbation and the associated response; the effect of a movement of residue i on residue j is not equal to that of the same movement of residue j on residue i.

  16. Identifying Ancient Settlement Patterns through LiDAR in the Mosquitia Region of Honduras.

    Directory of Open Access Journals (Sweden)

    Christopher T Fisher

    Full Text Available The Mosquitia ecosystem of Honduras occupies the fulcrum between the American continents and as such constitutes a critical region for understanding past patterns of socio-political development and interaction. Heavy vegetation, rugged topography, and remoteness have limited scientific investigation. This paper presents prehistoric patterns of settlement and landuse for a critical valley within the Mosquitia derived from airborne LiDAR scanning and field investigation. We show that (i though today the valley is a wilderness it was densely inhabited in the past; (ii that this population was organized into a three-tiered system composed of 19 settlements dominated by a city; and, (iii that this occupation was embedded within a human engineered landscape. We also add to a growing body of literature that demonstrates the utility of LiDAR as means for rapid cultural assessments in undocumented regions for analysis and conservation. Our ultimate hope is for our work to promote protections to safeguard the unique and critically endangered Mosquitia ecosystem and other similar areas in need of preservation.

  17. Identifying Ancient Settlement Patterns through LiDAR in the Mosquitia Region of Honduras

    Science.gov (United States)

    Fernández-Diaz, Juan Carlos; Cohen, Anna S.; Neil Cruz, Oscar; Gonzáles, Alicia M.; Leisz, Stephen J.; Pezzutti, Florencia; Shrestha, Ramesh; Carter, William

    2016-01-01

    The Mosquitia ecosystem of Honduras occupies the fulcrum between the American continents and as such constitutes a critical region for understanding past patterns of socio-political development and interaction. Heavy vegetation, rugged topography, and remoteness have limited scientific investigation. This paper presents prehistoric patterns of settlement and landuse for a critical valley within the Mosquitia derived from airborne LiDAR scanning and field investigation. We show that (i) though today the valley is a wilderness it was densely inhabited in the past; (ii) that this population was organized into a three-tiered system composed of 19 settlements dominated by a city; and, (iii) that this occupation was embedded within a human engineered landscape. We also add to a growing body of literature that demonstrates the utility of LiDAR as means for rapid cultural assessments in undocumented regions for analysis and conservation. Our ultimate hope is for our work to promote protections to safeguard the unique and critically endangered Mosquitia ecosystem and other similar areas in need of preservation. PMID:27560962

  18. Identifying Ancient Settlement Patterns through LiDAR in the Mosquitia Region of Honduras.

    Science.gov (United States)

    Fisher, Christopher T; Fernández-Diaz, Juan Carlos; Cohen, Anna S; Neil Cruz, Oscar; Gonzáles, Alicia M; Leisz, Stephen J; Pezzutti, Florencia; Shrestha, Ramesh; Carter, William

    2016-01-01

    The Mosquitia ecosystem of Honduras occupies the fulcrum between the American continents and as such constitutes a critical region for understanding past patterns of socio-political development and interaction. Heavy vegetation, rugged topography, and remoteness have limited scientific investigation. This paper presents prehistoric patterns of settlement and landuse for a critical valley within the Mosquitia derived from airborne LiDAR scanning and field investigation. We show that (i) though today the valley is a wilderness it was densely inhabited in the past; (ii) that this population was organized into a three-tiered system composed of 19 settlements dominated by a city; and, (iii) that this occupation was embedded within a human engineered landscape. We also add to a growing body of literature that demonstrates the utility of LiDAR as means for rapid cultural assessments in undocumented regions for analysis and conservation. Our ultimate hope is for our work to promote protections to safeguard the unique and critically endangered Mosquitia ecosystem and other similar areas in need of preservation.

  19. Identifying functional transcription factor binding sites in yeast by considering their positional preference in the promoters.

    Directory of Open Access Journals (Sweden)

    Fu-Jou Lai

    Full Text Available Transcription factor binding site (TFBS identification plays an important role in deciphering gene regulatory codes. With comprehensive knowledge of TFBSs, one can understand molecular mechanisms of gene regulation. In the recent decades, various computational approaches have been proposed to predict TFBSs in the genome. The TFBS dataset of a TF generated by each algorithm is a ranked list of predicted TFBSs of that TF, where top ranked TFBSs are statistically significant ones. However, whether these statistically significant TFBSs are functional (i.e. biologically relevant is still unknown. Here we develop a post-processor, called the functional propensity calculator (FPC, to assign a functional propensity to each TFBS in the existing computationally predicted TFBS datasets. It is known that functional TFBSs reveal strong positional preference towards the transcriptional start site (TSS. This motivates us to take TFBS position relative to the TSS as the key idea in building our FPC. Based on our calculated functional propensities, the TFBSs of a TF in the original TFBS dataset could be reordered, where top ranked TFBSs are now the ones with high functional propensities. To validate the biological significance of our results, we perform three published statistical tests to assess the enrichment of Gene Ontology (GO terms, the enrichment of physical protein-protein interactions, and the tendency of being co-expressed. The top ranked TFBSs in our reordered TFBS dataset outperform the top ranked TFBSs in the original TFBS dataset, justifying the effectiveness of our post-processor in extracting functional TFBSs from the original TFBS dataset. More importantly, assigning functional propensities to putative TFBSs enables biologists to easily identify which TFBSs in the promoter of interest are likely to be biologically relevant and are good candidates to do further detailed experimental investigation. The FPC is implemented as a web tool at http://santiago.ee.ncku.edu.tw/FPC/.

  20. Identifying Hot Spots of Critical Forage Supply in Dryland Nomadic Pastoralist Areas: A Case Study for the Afar Region, Ethiopia

    NARCIS (Netherlands)

    Sonneveld, B.G.J.S.; Keyzer, M.A.; van Wesenbeeck, C.F.A.; Georgis, Kidane; Beyene, Fekadu; Urbano, Ferdinando; Meroni, Michele; Leo, Olivier; Yimer, Merkebu; Abdullatif, Mohammed

    2017-01-01

    This study develops a methodology to identify hot spots of critical forage supply in nomadic pastoralist areas, using the Afar Region, Ethiopia, as a special case. It addresses two main problems. First, it makes a spatially explicit assessment of fodder supply and demand extracted from a data poor

  1. Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory.

    Science.gov (United States)

    Tanimizu, Toshiyuki; Kenney, Justin W; Okano, Emiko; Kadoma, Kazune; Frankland, Paul W; Kida, Satoshi

    2017-04-12

    Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory. SIGNIFICANCE STATEMENT Here, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We

  2. Identifying individuals at high risk of psychosis: predictive utility of Support Vector Machine using structural and functional MRI data

    Directory of Open Access Journals (Sweden)

    Isabel eValli

    2016-04-01

    Full Text Available The identification of individuals at high risk of developing psychosis is entirely based on clinical assessment, associated with limited predictive potential. There is therefore increasing interest in the development of biological markers that could be used in clinical practice for this purpose. We studied 25 individuals with an At Risk Mental State for psychosis and 25 healthy controls using structural MRI, and functional MRI in conjunction with a verbal memory task. Data were analysed using a standard univariate analysis, and with Support Vector Machine (SVM, a multivariate pattern recognition technique that enables statistical inferences to be made at the level of the individual, yielding results with high translational potential. The application of SVM to structural MRI data permitted the identification of individuals at high risk of psychosis with a sensitivity of 68% and a specificity of 76%, resulting in an accuracy of 72% (p<0.001. Univariate volumetric between-group differences did not reach statistical significance. In contrast, the univariate fMRI analysis identified between-group differences (p<0.05 corrected while the application of SVM to the same data did not. Since SVM is well suited at identifying the pattern of abnormality that distinguishes two groups, whereas univariate methods are more likely to identify regions that individually are most different between two groups, our results suggest the presence of focal functional abnormalities in the context of a diffuse pattern of structural abnormalities in individuals at high clinical risk of psychosis.

  3. A Statistical Method of Identifying Interactions in Neuron–Glia Systems Based on Functional Multicell Ca2+ Imaging

    Science.gov (United States)

    Nakae, Ken; Ikegaya, Yuji; Ishikawa, Tomoe; Oba, Shigeyuki; Urakubo, Hidetoshi; Koyama, Masanori; Ishii, Shin

    2014-01-01

    Crosstalk between neurons and glia may constitute a significant part of information processing in the brain. We present a novel method of statistically identifying interactions in a neuron–glia network. We attempted to identify neuron–glia interactions from neuronal and glial activities via maximum-a-posteriori (MAP)-based parameter estimation by developing a generalized linear model (GLM) of a neuron–glia network. The interactions in our interest included functional connectivity and response functions. We evaluated the cross-validated likelihood of GLMs that resulted from the addition or removal of connections to confirm the existence of specific neuron-to-glia or glia-to-neuron connections. We only accepted addition or removal when the modification improved the cross-validated likelihood. We applied the method to a high-throughput, multicellular in vitro Ca2+ imaging dataset obtained from the CA3 region of a rat hippocampus, and then evaluated the reliability of connectivity estimates using a statistical test based on a surrogate method. Our findings based on the estimated connectivity were in good agreement with currently available physiological knowledge, suggesting our method can elucidate undiscovered functions of neuron–glia systems. PMID:25393874

  4. The quality of clinical maternal and neonatal healthcare - a strategy for identifying 'routine care signal functions'.

    Directory of Open Access Journals (Sweden)

    Stephan Brenner

    Full Text Available A variety of clinical process indicators exists to measure the quality of care provided by maternal and neonatal health (MNH programs. To allow comparison across MNH programs in low- and middle-income countries (LMICs, a core set of essential process indicators is needed. Although such a core set is available for emergency obstetric care (EmOC, the 'EmOC signal functions', a similar approach is currently missing for MNH routine care evaluation. We describe a strategy for identifying core process indicators for routine care and illustrate their usefulness in a field example.We first developed an indicator selection strategy by combining epidemiological and programmatic aspects relevant to MNH in LMICs. We then identified routine care process indicators meeting our selection criteria by reviewing existing quality of care assessment protocols. We grouped these indicators into three categories based on their main function in addressing risk factors of maternal or neonatal complications. We then tested this indicator set in a study assessing MNH quality of clinical care in 33 health facilities in Malawi.Our strategy identified 51 routine care processes: 23 related to initial patient risk assessment, 17 to risk monitoring, 11 to risk prevention. During the clinical performance assessment a total of 82 cases were observed. Birth attendants' adherence to clinical standards was lowest in relation to risk monitoring processes. In relation to major complications, routine care processes addressing fetal and newborn distress were performed relatively consistently, but there were major gaps in the performance of routine care processes addressing bleeding, infection, and pre-eclampsia risks.The identified set of process indicators could identify major gaps in the quality of obstetric and neonatal care provided during the intra- and immediate postpartum period. We hope our suggested indicators for essential routine care processes will contribute to streamlining

  5. The quality of clinical maternal and neonatal healthcare - a strategy for identifying 'routine care signal functions'.

    Science.gov (United States)

    Brenner, Stephan; De Allegri, Manuela; Gabrysch, Sabine; Chinkhumba, Jobiba; Sarker, Malabika; Muula, Adamson S

    2015-01-01

    A variety of clinical process indicators exists to measure the quality of care provided by maternal and neonatal health (MNH) programs. To allow comparison across MNH programs in low- and middle-income countries (LMICs), a core set of essential process indicators is needed. Although such a core set is available for emergency obstetric care (EmOC), the 'EmOC signal functions', a similar approach is currently missing for MNH routine care evaluation. We describe a strategy for identifying core process indicators for routine care and illustrate their usefulness in a field example. We first developed an indicator selection strategy by combining epidemiological and programmatic aspects relevant to MNH in LMICs. We then identified routine care process indicators meeting our selection criteria by reviewing existing quality of care assessment protocols. We grouped these indicators into three categories based on their main function in addressing risk factors of maternal or neonatal complications. We then tested this indicator set in a study assessing MNH quality of clinical care in 33 health facilities in Malawi. Our strategy identified 51 routine care processes: 23 related to initial patient risk assessment, 17 to risk monitoring, 11 to risk prevention. During the clinical performance assessment a total of 82 cases were observed. Birth attendants' adherence to clinical standards was lowest in relation to risk monitoring processes. In relation to major complications, routine care processes addressing fetal and newborn distress were performed relatively consistently, but there were major gaps in the performance of routine care processes addressing bleeding, infection, and pre-eclampsia risks. The identified set of process indicators could identify major gaps in the quality of obstetric and neonatal care provided during the intra- and immediate postpartum period. We hope our suggested indicators for essential routine care processes will contribute to streamlining MNH program

  6. Selection on plant male function genes identifies candidates for reproductive isolation of yellow monkeyflowers.

    Directory of Open Access Journals (Sweden)

    Jan E Aagaard

    Full Text Available Understanding the genetic basis of reproductive isolation promises insight into speciation and the origins of biological diversity. While progress has been made in identifying genes underlying barriers to reproduction that function after fertilization (post-zygotic isolation, we know much less about earlier acting pre-zygotic barriers. Of particular interest are barriers involved in mating and fertilization that can evolve extremely rapidly under sexual selection, suggesting they may play a prominent role in the initial stages of reproductive isolation. A significant challenge to the field of speciation genetics is developing new approaches for identification of candidate genes underlying these barriers, particularly among non-traditional model systems. We employ powerful proteomic and genomic strategies to study the genetic basis of conspecific pollen precedence, an important component of pre-zygotic reproductive isolation among yellow monkeyflowers (Mimulus spp. resulting from male pollen competition. We use isotopic labeling in combination with shotgun proteomics to identify more than 2,000 male function (pollen tube proteins within maternal reproductive structures (styles of M. guttatus flowers where pollen competition occurs. We then sequence array-captured pollen tube exomes from a large outcrossing population of M. guttatus, and identify those genes with evidence of selective sweeps or balancing selection consistent with their role in pollen competition. We also test for evidence of positive selection on these genes more broadly across yellow monkeyflowers, because a signal of adaptive divergence is a common feature of genes causing reproductive isolation. Together the molecular evolution studies identify 159 pollen tube proteins that are candidate genes for conspecific pollen precedence. Our work demonstrates how powerful proteomic and genomic tools can be readily adapted to non-traditional model systems, allowing for genome-wide screens

  7. Identifying functional cancer-specific miRNA-mRNA interactions in testicular germ cell tumor.

    Science.gov (United States)

    Sedaghat, Nafiseh; Fathy, Mahmood; Modarressi, Mohammad Hossein; Shojaie, Ali

    2016-09-07

    Testicular cancer is the most common cancer in men aged between 15 and 35 and more than 90% of testicular neoplasms are originated at germ cells. Recent research has shown the impact of microRNAs (miRNAs) in different types of cancer, including testicular germ cell tumor (TGCT). MicroRNAs are small non-coding RNAs which affect the development and progression of cancer cells by binding to mRNAs and regulating their expressions. The identification of functional miRNA-mRNA interactions in cancers, i.e. those that alter the expression of genes in cancer cells, can help delineate post-regulatory mechanisms and may lead to new treatments to control the progression of cancer. A number of sequence-based methods have been developed to predict miRNA-mRNA interactions based on the complementarity of sequences. While necessary, sequence complementarity is, however, not sufficient for presence of functional interactions. Alternative methods have thus been developed to refine the sequence-based interactions using concurrent expression profiles of miRNAs and mRNAs. This study aims to find functional cancer-specific miRNA-mRNA interactions in TGCT. To this end, the sequence-based predicted interactions are first refined using an ensemble learning method, based on two well-known methods of learning miRNA-mRNA interactions, namely, TaLasso and GenMiR++. Additional functional analyses were then used to identify a subset of interactions to be most likely functional and specific to TGCT. The final list of 13 miRNA-mRNA interactions can be potential targets for identifying TGCT-specific interactions and future laboratory experiments to develop new therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. TESTING SOME PEDO-TRANSFER FUNCTIONS (PTFS IN APULIA REGION

    Directory of Open Access Journals (Sweden)

    Floriano Buccigrossi

    2009-03-01

    Full Text Available The knowledge of soil water retention vs. soil water matric potential is used to study irrigation and drainage schedules, soil water storage capacity (plant available water, solute movement, plant growth and water stress. The hydraulic soil properties measuring is expensive, laborious and takes too long time, so, frequently, matemathic models, called pedo-transfer functions (PTFs are utilized to estimate hydraulic soil properties through soil chimical and phisical characteristics. Six pedo-transfer functions have been evaluated (Gupta & Larson, 1979; Rawls et al., 1982; De Jong et al., 1983; Rawls & Brakensiek, 1985; Saxton et al., 1986; Vereecken et al., 1989 by comparing estimated with measured soil moisture values at soil water matric potential of –33 and –1500 kPa of 361 soil samples collected from 185 pedons of Apulia Region (South Italy, having various combinations of particle-size distribution, soil organic matter content and bulk density. Accuracy of the soil moisture predictions have been evaluated by statistic indexes such as Weighted stantard error (WSEE, Mean Deviation (MD, Root Mean Squared Deviation (RMSD and the determination coefficient (R2 between estimated and measured water retention values. The Rawls PTF model demostrated to have the lowest values of WSEE, MD and RMSD indexes (0.044, -0.007 and 0.059 m3 H2O m-3 soil, respectively at –33 Kpa soil water matric potential (Field Capacity, while for estimating soil moisture at the Wilting Point (-1500 kPa Rawls & Brakensiek model is adequate (WSEE, MD and RMSD of 0.034, -0.016 and 0.046 m3 H2O m-3 soil. De Jong, Saxton and Rawls & Brakensiek models, at –33 kPa soil water matric potential and Gupta & Larson and De Jong models at –1500 kPa soil water matric potential, showed the highest statistic errors.

  9. Generalized query-based active learning to identify differentially methylated regions in DNA.

    Science.gov (United States)

    Haque, Md Muksitul; Holder, Lawrence B; Skinner, Michael K; Cook, Diane J

    2013-01-01

    Active learning is a supervised learning technique that reduces the number of examples required for building a successful classifier, because it can choose the data it learns from. This technique holds promise for many biological domains in which classified examples are expensive and time-consuming to obtain. Most traditional active learning methods ask very specific queries to the Oracle (e.g., a human expert) to label an unlabeled example. The example may consist of numerous features, many of which are irrelevant. Removing such features will create a shorter query with only relevant features, and it will be easier for the Oracle to answer. We propose a generalized query-based active learning (GQAL) approach that constructs generalized queries based on multiple instances. By constructing appropriately generalized queries, we can achieve higher accuracy compared to traditional active learning methods. We apply our active learning method to find differentially DNA methylated regions (DMRs). DMRs are DNA locations in the genome that are known to be involved in tissue differentiation, epigenetic regulation, and disease. We also apply our method on 13 other data sets and show that our method is better than another popular active learning technique.

  10. How to identify rectal sub-regions likely involved in rectal bleeding in prostate cancer radiotherapy

    Science.gov (United States)

    Dréan, G.; Acosta, O.; Ospina, J. D.; Voisin, C.; Rigaud, B.; Simon, A.; Haigron, P.; de Crevoisier, R.

    2013-11-01

    Nowadays, the de nition of patient-speci c constraints in prostate cancer radiotherapy planning are solely based on dose-volume histogram (DVH) parameters. Nevertheless those DVH models lack of spatial accuracy since they do not use the complete 3D information of the dose distribution. The goal of the study was to propose an automatic work ow to de ne patient-speci c rectal sub-regions (RSR) involved in rectal bleeding (RB) in case of prostate cancer radiotherapy. A multi-atlas database spanning the large rectal shape variability was built from a population of 116 individuals. Non-rigid registration followed by voxel-wise statistical analysis on those templates allowed nding RSR likely correlated with RB (from a learning cohort of 63 patients). To de ne patient-speci c RSR, weighted atlas-based segmentation with a vote was then applied to 30 test patients. Results show the potentiality of the method to be used for patient-speci c planning of intensity modulated radiotherapy (IMRT).

  11. Immunochip analysis identifies association of the RAD50/IL13 region with human longevity

    DEFF Research Database (Denmark)

    Flachsbart, Friederike; Ellinghaus, David; Gentschew, Liljana

    2016-01-01

    Human longevity is characterized by a remarkable lack of confirmed genetic associations. Here, we report on the identification of a novel locus for longevity in the RAD50/IL13 region on chromosome 5q31.1 using a combined European sample of 3208 long-lived individuals (LLI) and 8919 younger controls....... First, we performed a large-scale association study on 1458 German LLI (mean age 99.0 years) and 6368 controls (mean age 57.2 years) by targeting known immune-associated loci covered by the Immunochip. The analysis of 142 136 autosomal single nucleotide polymorphisms (SNPs) revealed an Immunochip...... (1257 LLI, mean age 102.4 years; 1811 controls, mean age 49.1 years) and Denmark (493 LLI, mean age 96.2 years; 740 controls, mean age 63.1 years). The association at SNP rs2706372 replicated in the French study collection and showed a similar trend in the Danish participants and was also significant...

  12. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity

    Science.gov (United States)

    Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I.; Taylor, Kent D.; Azziz, Ricardo; Goodarzi, Mark O.

    2015-01-01

    Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS. PMID:26305227

  13. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity.

    Directory of Open Access Journals (Sweden)

    Michelle R Jones

    2015-08-01

    Full Text Available Genome wide association studies (GWAS have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS, a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS.

  14. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity.

    Science.gov (United States)

    Jones, Michelle R; Brower, Meredith A; Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I; Taylor, Kent D; Azziz, Ricardo; Goodarzi, Mark O

    2015-08-01

    Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS.

  15. In vitro functional screening as a means to identify new plasticizers devoid of reproductive toxicity

    International Nuclear Information System (INIS)

    Boisvert, Annie; Jones, Steven; Issop, Leeyah; Erythropel, Hanno C.; Papadopoulos, Vassilios; Culty, Martine

    2016-01-01

    Plasticizers are indispensable additives providing flexibility and malleability to plastics. Among them, several phthalates, including di (2-ethylhexyl) phthalate (DEHP), have emerged as endocrine disruptors, leading to their restriction in consumer products and creating a need for new, safer plasticizers. The goal of this project was to use in vitro functional screening tools to select novel non-toxic plasticizers suitable for further in vivo evaluation. A panel of novel compounds with satisfactory plasticizer properties and biodegradability were tested, along with several commercial plasticizers, such as diisononyl-cyclohexane-1,2-dicarboxylate (DINCH®). MEHP, the monoester metabolite of DEHP was also included as reference compound. Because phthalates target mainly testicular function, including androgen production and spermatogenesis, we used the mouse MA-10 Leydig and C18-4 spermatogonial cell lines as surrogates to examine cell survival, proliferation, steroidogenesis and mitochondrial integrity. The most promising compounds were further assessed on organ cultures of rat fetal and neonatal testes, corresponding to sensitive developmental windows. Dose-response studies revealed the toxicity of most maleates and fumarates, while identifying several dibenzoate and succinate plasticizers as innocuous on Leydig and germ cells. Interestingly, DINCH®, a plasticizer marketed as a safe alternative to phthalates, exerted a biphasic effect on steroid production in MA-10 and fetal Leydig cells. MEHP was the only plasticizer inducing the formation of multinucleated germ cells (MNG) in organ culture. Overall, organ cultures corroborated the cell line data, identifying one dibenzoate and one succinate as the most promising candidates. The adoption of such collaborative approaches for developing new chemicals should help prevent the development of compounds potentially harmful to human health. - Highlights: • Phthalate plasticizers exert toxic effects on male reproduction

  16. Identifying functional reorganization of spelling networks: an individual peak probability comparison approach

    Science.gov (United States)

    Purcell, Jeremy J.; Rapp, Brenda

    2013-01-01

    Previous research has shown that damage to the neural substrates of orthographic processing can lead to functional reorganization during reading (Tsapkini et al., 2011); in this research we ask if the same is true for spelling. To examine the functional reorganization of spelling networks we present a novel three-stage Individual Peak Probability Comparison (IPPC) analysis approach for comparing the activation patterns obtained during fMRI of spelling in a single brain-damaged individual with dysgraphia to those obtained in a set of non-impaired control participants. The first analysis stage characterizes the convergence in activations across non-impaired control participants by applying a technique typically used for characterizing activations across studies: Activation Likelihood Estimate (ALE) (Turkeltaub et al., 2002). This method was used to identify locations that have a high likelihood of yielding activation peaks in the non-impaired participants. The second stage provides a characterization of the degree to which the brain-damaged individual's activations correspond to the group pattern identified in Stage 1. This involves performing a Mahalanobis distance statistics analysis (Tsapkini et al., 2011) that compares each of a control group's peak activation locations to the nearest peak generated by the brain-damaged individual. The third stage evaluates the extent to which the brain-damaged individual's peaks are atypical relative to the range of individual variation among the control participants. This IPPC analysis allows for a quantifiable, statistically sound method for comparing an individual's activation pattern to the patterns observed in a control group and, thus, provides a valuable tool for identifying functional reorganization in a brain-damaged individual with impaired spelling. Furthermore, this approach can be applied more generally to compare any individual's activation pattern with that of a set of other individuals. PMID:24399981

  17. In vitro functional screening as a means to identify new plasticizers devoid of reproductive toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Boisvert, Annie; Jones, Steven; Issop, Leeyah [The Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Erythropel, Hanno C. [Department of Chemical Engineering, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Papadopoulos, Vassilios [The Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Culty, Martine, E-mail: martine.culty@mcgill.ca [The Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada)

    2016-10-15

    Plasticizers are indispensable additives providing flexibility and malleability to plastics. Among them, several phthalates, including di (2-ethylhexyl) phthalate (DEHP), have emerged as endocrine disruptors, leading to their restriction in consumer products and creating a need for new, safer plasticizers. The goal of this project was to use in vitro functional screening tools to select novel non-toxic plasticizers suitable for further in vivo evaluation. A panel of novel compounds with satisfactory plasticizer properties and biodegradability were tested, along with several commercial plasticizers, such as diisononyl-cyclohexane-1,2-dicarboxylate (DINCH®). MEHP, the monoester metabolite of DEHP was also included as reference compound. Because phthalates target mainly testicular function, including androgen production and spermatogenesis, we used the mouse MA-10 Leydig and C18-4 spermatogonial cell lines as surrogates to examine cell survival, proliferation, steroidogenesis and mitochondrial integrity. The most promising compounds were further assessed on organ cultures of rat fetal and neonatal testes, corresponding to sensitive developmental windows. Dose-response studies revealed the toxicity of most maleates and fumarates, while identifying several dibenzoate and succinate plasticizers as innocuous on Leydig and germ cells. Interestingly, DINCH®, a plasticizer marketed as a safe alternative to phthalates, exerted a biphasic effect on steroid production in MA-10 and fetal Leydig cells. MEHP was the only plasticizer inducing the formation of multinucleated germ cells (MNG) in organ culture. Overall, organ cultures corroborated the cell line data, identifying one dibenzoate and one succinate as the most promising candidates. The adoption of such collaborative approaches for developing new chemicals should help prevent the development of compounds potentially harmful to human health. - Highlights: • Phthalate plasticizers exert toxic effects on male reproduction

  18. Hotspots of missense mutation identify novel neurodevelopmental disorder genes and functional domains

    Science.gov (United States)

    Geisheker, Madeleine R.; Heymann, Gabriel; Wang, Tianyun; Coe, Bradley P.; Turner, Tychele N.; Stessman, Holly A.F.; Hoekzema, Kendra; Kvarnung, Malin; Shaw, Marie; Friend, Kathryn; Liebelt, Jan; Barnett, Christopher; Thompson, Elizabeth M.; Haan, Eric; Guo, Hui; Anderlid, Britt-Marie; Nordgren, Ann; Lindstrand, Anna; Vandeweyer, Geert; Alberti, Antonino; Avola, Emanuela; Vinci, Mirella; Giusto, Stefania; Pramparo, Tiziano; Pierce, Karen; Nalabolu, Srinivasa; Michaelson, Jacob J.; Sedlacek, Zdenek; Santen, Gijs W.E.; Peeters, Hilde; Hakonarson, Hakon; Courchesne, Eric; Romano, Corrado; Kooy, R. Frank; Bernier, Raphael A.; Nordenskjöld, Magnus; Gecz, Jozef; Xia, Kun; Zweifel, Larry S.; Eichler, Evan E.

    2017-01-01

    Although de novo missense mutations have been predicted to account for more cases of autism than gene-truncating mutations, most research has focused on the latter. We identified the properties of de novo missense mutations in patients with neurodevelopmental disorders (NDDs) and highlight 35 genes with excess missense mutations. Additionally, 40 amino acid sites were recurrently mutated in 36 genes, and targeted sequencing of 20 sites in 17,689 NDD patients identified 21 new patients with identical missense mutations. One recurrent site (p.Ala636Thr) occurs in a glutamate receptor subunit, GRIA1. This same amino acid substitution in the homologous but distinct mouse glutamate receptor subunit Grid2 is associated with Lurcher ataxia. Phenotypic follow-up in five individuals with GRIA1 mutations shows evidence of specific learning disabilities and autism. Overall, we find significant clustering of de novo mutations in 200 genes, highlighting specific functional domains and synaptic candidate genes important in NDD pathology. PMID:28628100

  19. Enu mutagenesis identifies a novel platelet phenotype in a loss-of-function Jak2 allele.

    Directory of Open Access Journals (Sweden)

    Nicole M Anderson

    Full Text Available Utilizing ENU mutagenesis, we identified a mutant mouse with elevated platelets. Genetic mapping localized the mutation to an interval on chromosome 19 that encodes the Jak2 tyrosine kinase. We identified a A3056T mutation resulting in a premature stop codon within exon 19 of Jak2 (Jak2(K915X, resulting in a protein truncation and functionally inactive enzyme. This novel platelet phenotype was also observed in mice bearing a hemizygous targeted disruption of the Jak2 locus (Jak2(+/-. Timed pregnancy experiments revealed that Jak2(K915X/K915X and Jak2(-/- displayed embryonic lethality; however, Jak2(K915X/K915X embryos were viable an additional two days compared to Jak2(-/- embryos. Our data suggest that perturbing JAK2 activation may have unexpected consequences in elevation of platelet number and correspondingly, important implications for treatment of hematological disorders with constitutive Jak2 activity.

  20. Enterococcus phages as potential tool for identifying sewage inputs in the Great Lakes region

    Science.gov (United States)

    Vijayavel, K.; Byappanahalli, Muruleedhara N.; Whitman, Richard L.; Ebdon, J.; Taylor, H.; Kashian, D.R.

    2014-01-01

    Bacteriophages are viruses living in bacteria that can be used as a tool to detect fecal contamination in surface waters around the world. However, the lack of a universal host strain makes them unsuitable for tracking fecal sources. We evaluated the suitability of two newly isolated Enterococcus host strains (ENT-49 and ENT-55) capable for identifying sewage contamination in impacted waters by targeting phages specific to these hosts. Both host strains were isolated from wastewater samples and identified as E. faecium by 16S rRNA gene sequencing. Occurrence of Enterococcus phages was evaluated in sewage samples (n = 15) from five wastewater treatment plants and in fecal samples from twenty-two species of wild and domesticated animals (individual samples; n = 22). Levels of Enterococcus phages, F + coliphages, Escherichia coli and enterococci were examined from four rivers, four beaches, and three harbors. Enterococcus phages enumeration was at similar levels (Mean = 6.72 Log PFU/100 mL) to F + coliphages in all wastewater samples, but were absent from all non-human fecal sources tested. The phages infecting Enterococcus spp. and F + coliphages were not detected in the river samples (detection threshold < 10 PFU/100 mL), but were present in the beach and harbor samples (range = 1.83 to 2.86 Log PFU/100 mL). Slightly higher concentrations (range = 3.22 to 3.69 Log MPN/100 mL) of E. coli and enterococci when compared to F + coliphages and Enterococcus phages, were observed in the river, beach and harbor samples. Our findings suggest that the bacteriophages associated with these particular Enterococcus host strains offer potentially sensitive and human-source specific indicators of enteric pathogen risk.

  1. A statistical framework to predict functional non-coding regions in the human genome through integrated analysis of annotation data.

    Science.gov (United States)

    Lu, Qiongshi; Hu, Yiming; Sun, Jiehuan; Cheng, Yuwei; Cheung, Kei-Hoi; Zhao, Hongyu

    2015-05-27

    Identifying functional regions in the human genome is a major goal in human genetics. Great efforts have been made to functionally annotate the human genome either through computational predictions, such as genomic conservation, or high-throughput experiments, such as the ENCODE project. These efforts have resulted in a rich collection of functional annotation data of diverse types that need to be jointly analyzed for integrated interpretation and annotation. Here we present GenoCanyon, a whole-genome annotation method that performs unsupervised statistical learning using 22 computational and experimental annotations thereby inferring the functional potential of each position in the human genome. With GenoCanyon, we are able to predict many of the known functional regions. The ability of predicting functional regions as well as its generalizable statistical framework makes GenoCanyon a unique and powerful tool for whole-genome annotation. The GenoCanyon web server is available at http://genocanyon.med.yale.edu.

  2. Unique Trichomonas vaginalis gene sequences identified in multinational regions of Northwest China.

    Science.gov (United States)

    Liu, Jun; Feng, Meng; Wang, Xiaolan; Fu, Yongfeng; Ma, Cailing; Cheng, Xunjia

    2017-07-24

    Trichomonas vaginalis (T. vaginalis) is a flagellated protozoan parasite that infects humans worldwide. This study determined the sequence of the 18S ribosomal RNA gene of T. vaginalis infecting both females and males in Xinjiang, China. Samples from 73 females and 28 males were collected and confirmed for infection with T. vaginalis, a total of 110 sequences were identified when the T. vaginalis 18S ribosomal RNA gene was sequenced. These sequences were used to prepare a phylogenetic network. The rooted network comprised three large clades and several independent branches. Most of the Xinjiang sequences were in one group. Preliminary results suggest that Xinjiang T. vaginalis isolates might be genetically unique, as indicated by the sequence of their 18S ribosomal RNA gene. Low migration rate of local people in this province may contribute to a genetic conservativeness of T. vaginalis. The unique genetic feature of our isolates may suggest a different clinical presentation of trichomoniasis, including metronidazole susceptibility, T. vaginalis virus or Mycoplasma co-infection characteristics. The transmission and evolution of Xinjiang T. vaginalis is of interest and should be studied further. More attention should be given to T. vaginalis infection in both females and males in Xinjiang.

  3. Integrated Pathway-Based Approach Identifies Association between Genomic Regions at CTCF and CACNB2 and Schizophrenia

    NARCIS (Netherlands)

    Juraeva, Dilafruz; Haenisch, Britta; Zapatka, Marc; Frank, Josef; Witt, Stephanie H.; Mühleisen, Thomas W.; Treutlein, Jens; Strohmaier, Jana; Meier, Sandra; Degenhardt, Franziska; Giegling, Ina; Ripke, Stephan; Leber, Markus; Lange, Christoph; Schulze, Thomas G.; Mössner, Rainald; Nenadic, Igor; Sauer, Heinrich; Rujescu, Dan; Maier, Wolfgang; Børglum, Anders; Ophoff, Roel; Cichon, Sven; Nöthen, Markus M.; Rietschel, Marcella; Mattheisen, Manuel; Brors, Benedikt; Kahn, René S.; Cahn, Wiepke; Linszen, Don H.; de Haan, Lieuwe; van Os, Jim; Krabbendam, Lydia; Myin-Germeys, Inez; Wiersma, Durk; Bruggeman, Richard; Mors, O.; Børglum, A. D.; Mortensen, P. B.; Pedersen, C. B.; Demontis, D.; Grove, J.; Mattheisen, M.; Hougaard, D. M.

    2014-01-01

    In the present study, an integrated hierarchical approach was applied to: (1) identify pathways associated with susceptibility to schizophrenia; (2) detect genes that may be potentially affected in these pathways since they contain an associated polymorphism; and (3) annotate the functional

  4. Function of C-terminal hydrophobic region in fructose dehydrogenase

    International Nuclear Information System (INIS)

    Sugimoto, Yu; Kawai, Shota; Kitazumi, Yuki; Shirai, Osamu; Kano, Kenji

    2015-01-01

    Fructose dehydrogenase (FDH) catalyzes oxidation of D-fructose into 2-keto-D-fructose and is one of the enzymes allowing a direct electron transfer (DET)-type bioelectrocatalysis. FDH is a heterotrimeric membrane-bound enzyme (subunit I, II, and III) and subunit II has a C terminal hydrophobic region (CHR), which was expected to play a role in anchoring to membranes from the amino acid sequence. We have constructed a mutated FDH lacking of CHR (ΔchrFDH). Contrary to the expected function of CHR, ΔchrFDH is expressed in the membrane fraction, and subunit I/III subcomplex (ΔcFDH) is also expressed in a similar activity level but in the soluble fraction. In addition, the enzyme activity of the purified ΔchrFDH is about one twentieth of the native FDH. These results indicate that CHR is concerned with the binding between subunit I(/III) and subunit II and then with the enzyme activity. ΔchrFDH has clear DET activity that is larger than that expected from the solution activity, and the characteristics of the catalytic wave of ΔchrFDH are very similar to those of FDH. The deletion of CHR seems to increase the amounts of the enzyme with the proper orientation for the DET reaction at electrode surfaces. Gel filtration chromatography coupled with urea treatment shows that the binding in ΔchrFDH is stronger than that in FDH. It can be considered that the rigid binding between subunit I(/III) and II without CHR results in a conformation different from the native one, which leads to the decrease in the enzyme activity in solution

  5. Characterization of the equine skeletal muscle transcriptome identifies novel functional responses to exercise training.

    LENUS (Irish Health Repository)

    McGivney, Beatrice A

    2010-01-01

    BACKGROUND: Digital gene expression profiling was used to characterize the assembly of genes expressed in equine skeletal muscle and to identify the subset of genes that were differentially expressed following a ten-month period of exercise training. The study cohort comprised seven Thoroughbred racehorses from a single training yard. Skeletal muscle biopsies were collected at rest from the gluteus medius at two time points: T(1) - untrained, (9 +\\/- 0.5 months old) and T(2) - trained (20 +\\/- 0.7 months old). RESULTS: The most abundant mRNA transcripts in the muscle transcriptome were those involved in muscle contraction, aerobic respiration and mitochondrial function. A previously unreported over-representation of genes related to RNA processing, the stress response and proteolysis was observed. Following training 92 tags were differentially expressed of which 74 were annotated. Sixteen genes showed increased expression, including the mitochondrial genes ACADVL, MRPS21 and SLC25A29 encoded by the nuclear genome. Among the 58 genes with decreased expression, MSTN, a negative regulator of muscle growth, had the greatest decrease.Functional analysis of all expressed genes using FatiScan revealed an asymmetric distribution of 482 Gene Ontology (GO) groups and 18 KEGG pathways. Functional groups displaying highly significant (P < 0.0001) increased expression included mitochondrion, oxidative phosphorylation and fatty acid metabolism while functional groups with decreased expression were mainly associated with structural genes and included the sarcoplasm, laminin complex and cytoskeleton. CONCLUSION: Exercise training in Thoroughbred racehorses results in coordinate changes in the gene expression of functional groups of genes related to metabolism, oxidative phosphorylation and muscle structure.

  6. Identifying functional groups for response to disturbance in an abandoned pasture

    Science.gov (United States)

    Lavorel, Sandra; Touzard, Blaise; Lebreton, Jean-Dominique; Clément, Bernard

    1998-06-01

    In an abandoned pasture in Brittany, we compared artificial small-scale disturbances to natural disturbances by wild boar and undisturbed vegetation. We developed a multivariate statistical approach which analyses how species biological attributes explain the response of community composition to disturbances. This technique, which reconciles the inductive and deductive approaches for functional classifications, identifies groups of species with similar responses to disturbance and characterizes their biological profiles. After 5 months of recolonization, artificial disturbances had a greater species richness than undisturbed vegetation as a result of recruitment of new species without the exclusion of pre-existing matrix species. Species morphology, described by canopy structure, canopy height and lateral spread, explained a large part (16 %) of community response to disturbance. Regeneration strategies, described by life history, seed mass, dispersal agent, dormancy and the existence of vegetative multiplication, explained a smaller part of community response to disturbance (8 %). Artificial disturbances were characterized by therophyte and compact rosettes with moderately dormant seeds, including a number of Asteraceae and other early successional species. Natural disturbances were colonized by leafy guerrilla species without seed dormancy. Few species were tightly related to undisturbed vegetation and were essentially grasses with a phalanx rosette morphology. The functional classification obtained is consistent with the classification of the community into fugitives, regenerators and persistors. These groups are structured according to Grubb's model for temperate grasslands, with regenerators and persistors in the matrix and fugitives taking advantage of gaps open by small-scale disturbances. The conjunction of functional diversity and species diversity within functional groups is the key to resilience to disturbance, an important ecosystem function.

  7. In Vivo Functional Selection Identifies Cardiotrophin-1 as a Cardiac Engraftment Factor for Mesenchymal Stromal Cells.

    Science.gov (United States)

    Bortolotti, Francesca; Ruozi, Giulia; Falcione, Antonella; Doimo, Sara; Dal Ferro, Matteo; Lesizza, Pierluigi; Zentilin, Lorena; Banks, Lawrence; Zacchigna, Serena; Giacca, Mauro

    2017-10-17

    Transplantation of cells into the infarcted heart has significant potential to improve myocardial recovery; however, low efficacy of cell engraftment still limits therapeutic benefit. Here, we describe a method for the unbiased, in vivo selection of cytokines that improve mesenchymal stromal cell engraftment into the heart both in normal conditions and after myocardial infarction. An arrayed library of 80 secreted factors, including most of the currently known interleukins and chemokines, were individually cloned into adeno-associated viral vectors. Pools from this library were then used for the batch transduction of bone marrow-derived mesenchymal stromal cells ex vivo, followed by intramyocardial cell administration in normal and infarcted mice. Three weeks after injection, vector genomes were recovered from the few persisting cells and identified by sequencing DNA barcodes uniquely labeling each of the tested cytokines. The most effective molecule identified by this competitive engraftment screening was cardiotrophin-1, a member of the interleukin-6 family. Intracardiac injection of mesenchymal stromal cells transiently preconditioned with cardiotrophin-1 preserved cardiac function and reduced infarct size, parallel to the persistence of the transplanted cells in the healing hearts for at least 2 months after injection. Engraftment of cardiotrophin-1-treated mesenchymal stromal cells was consequent to signal transducer and activator of transcription 3-mediated activation of the focal adhesion kinase and its associated focal adhesion complex and the consequent acquisition of adhesive properties by the cells. These results support the feasibility of selecting molecules in vivo for their functional properties with adeno-associated viral vector libraries and identify cardiotrophin-1 as a powerful cytokine promoting cell engraftment and thus improving cell therapy of the infarcted myocardium. © 2017 American Heart Association, Inc.

  8. Chromosomal microarray testing identifies a 4p terminal region associated with seizures in Wolf–Hirschhorn syndrome

    Science.gov (United States)

    South, Sarah T; Lortz, Amanda; Hensel, Charles H; Sdano, Mallory R; Vanzo, Rena J; Martin, Megan M; Peiffer, Andreas; Lambert, Christophe G; Calhoun, Amy; Carey, John C; Battaglia, Agatino

    2016-01-01

    Background Wolf–Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving variable size deletions of the 4p16.3 region. Seizures are frequently, but not always, associated with WHS. We hypothesised that the size and location of the deleted region may correlate with seizure presentation. Methods Using chromosomal microarray analysis, we finely mapped the breakpoints of copy number variants (CNVs) in 48 individuals with WHS. Seizure phenotype data were collected through parent-reported answers to a comprehensive questionnaire and supplemented with available medical records. Results We observed a significant correlation between the presence of an interstitial 4p deletion and lack of a seizure phenotype (Fisher's exact test p=3.59e-6). In our cohort, there were five individuals with interstitial deletions with a distal breakpoint at least 751 kbp proximal to the 4p terminus. Four of these individuals have never had an observable seizure, and the fifth individual had a single febrile seizure at the age of 1.5 years. All other individuals in our cohort whose deletions encompass the terminal 751 kbp region report having seizures typical of WHS. Additional examples from the literature corroborate these observations and further refine the candidate seizure susceptibility region to a region 197 kbp in size, starting 368 kbp from the terminus of chromosome 4. Conclusions We identify a small terminal region of chromosome 4p that represents a seizure susceptibility region. Deletion of this region in the context of WHS is sufficient for seizure occurrence. PMID:26747863

  9. Chromosomal microarray testing identifies a 4p terminal region associated with seizures in Wolf-Hirschhorn syndrome.

    Science.gov (United States)

    Ho, Karen S; South, Sarah T; Lortz, Amanda; Hensel, Charles H; Sdano, Mallory R; Vanzo, Rena J; Martin, Megan M; Peiffer, Andreas; Lambert, Christophe G; Calhoun, Amy; Carey, John C; Battaglia, Agatino

    2016-04-01

    Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving variable size deletions of the 4p16.3 region. Seizures are frequently, but not always, associated with WHS. We hypothesised that the size and location of the deleted region may correlate with seizure presentation. Using chromosomal microarray analysis, we finely mapped the breakpoints of copy number variants (CNVs) in 48 individuals with WHS. Seizure phenotype data were collected through parent-reported answers to a comprehensive questionnaire and supplemented with available medical records. We observed a significant correlation between the presence of an interstitial 4p deletion and lack of a seizure phenotype (Fisher's exact test p=3.59e-6). In our cohort, there were five individuals with interstitial deletions with a distal breakpoint at least 751 kbp proximal to the 4p terminus. Four of these individuals have never had an observable seizure, and the fifth individual had a single febrile seizure at the age of 1.5 years. All other individuals in our cohort whose deletions encompass the terminal 751 kbp region report having seizures typical of WHS. Additional examples from the literature corroborate these observations and further refine the candidate seizure susceptibility region to a region 197 kbp in size, starting 368 kbp from the terminus of chromosome 4. We identify a small terminal region of chromosome 4p that represents a seizure susceptibility region. Deletion of this region in the context of WHS is sufficient for seizure occurrence. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  10. Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis.

    Science.gov (United States)

    Khavari, Rose; Karmonik, Christof; Shy, Michael; Fletcher, Sophie; Boone, Timothy

    2017-02-01

    Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas

  11. A survey of single nucleotide polymorphisms identified from whole-genome sequencing and their functional effect in the porcine genome.

    Science.gov (United States)

    Keel, B N; Nonneman, D J; Rohrer, G A

    2017-08-01

    Genetic variants detected from sequence have been used to successfully identify causal variants and map complex traits in several organisms. High and moderate impact variants, those expected to alter or disrupt the protein coded by a gene and those that regulate protein production, likely have a more significant effect on phenotypic variation than do other types of genetic variants. Hence, a comprehensive list of these functional variants would be of considerable interest in swine genomic studies, particularly those targeting fertility and production traits. Whole-genome sequence was obtained from 72 of the founders of an intensely phenotyped experimental swine herd at the U.S. Meat Animal Research Center (USMARC). These animals included all 24 of the founding boars (12 Duroc and 12 Landrace) and 48 Yorkshire-Landrace composite sows. Sequence reads were mapped to the Sscrofa10.2 genome build, resulting in a mean of 6.1 fold (×) coverage per genome. A total of 22 342 915 high confidence SNPs were identified from the sequenced genomes. These included 21 million previously reported SNPs and 79% of the 62 163 SNPs on the PorcineSNP60 BeadChip assay. Variation was detected in the coding sequence or untranslated regions (UTRs) of 87.8% of the genes in the porcine genome: loss-of-function variants were predicted in 504 genes, 10 202 genes contained nonsynonymous variants, 10 773 had variation in UTRs and 13 010 genes contained synonymous variants. Approximately 139 000 SNPs were classified as loss-of-function, nonsynonymous or regulatory, which suggests that over 99% of the variation detected in our pigs could potentially be ignored, allowing us to focus on a much smaller number of functional SNPs during future analyses. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  12. Use of multilevel logistic regression to identify the causes of differential item functioning.

    Science.gov (United States)

    Balluerka, Nekane; Gorostiaga, Arantxa; Gómez-Benito, Juana; Hidalgo, María Dolores

    2010-11-01

    Given that a key function of tests is to serve as evaluation instruments and for decision making in the fields of psychology and education, the possibility that some of their items may show differential behaviour is a major concern for psychometricians. In recent decades, important progress has been made as regards the efficacy of techniques designed to detect this differential item functioning (DIF). However, the findings are scant when it comes to explaining its causes. The present study addresses this problem from the perspective of multilevel analysis. Starting from a case study in the area of transcultural comparisons, multilevel logistic regression is used: 1) to identify the item characteristics associated with the presence of DIF; 2) to estimate the proportion of variation in the DIF coefficients that is explained by these characteristics; and 3) to evaluate alternative explanations of the DIF by comparing the explanatory power or fit of different sequential models. The comparison of these models confirmed one of the two alternatives (familiarity with the stimulus) and rejected the other (the topic area) as being a cause of differential functioning with respect to the compared groups.

  13. Identifying and Visualizing Functional PAM Diversity across CRISPR-Cas Systems.

    Science.gov (United States)

    Leenay, Ryan T; Maksimchuk, Kenneth R; Slotkowski, Rebecca A; Agrawal, Roma N; Gomaa, Ahmed A; Briner, Alexandra E; Barrangou, Rodolphe; Beisel, Chase L

    2016-04-07

    CRISPR-Cas adaptive immune systems in prokaryotes boast a diversity of protein families and mechanisms of action, where most systems rely on protospacer-adjacent motifs (PAMs) for DNA target recognition. Here, we developed an in vivo, positive, and tunable screen termed PAM-SCANR (PAM screen achieved by NOT-gate repression) to elucidate functional PAMs as well as an interactive visualization scheme termed the PAM wheel to convey individual PAM sequences and their activities. PAM-SCANR and the PAM wheel identified known functional PAMs while revealing complex sequence-activity landscapes for the Bacillus halodurans I-C (Cascade), Escherichia coli I-E (Cascade), Streptococcus thermophilus II-A CRISPR1 (Cas9), and Francisella novicida V-A (Cpf1) systems. The PAM wheel was also readily applicable to existing high-throughput screens and garnered insights into SpyCas9 and SauCas9 PAM diversity. These tools offer powerful means of elucidating and visualizing functional PAMs toward accelerating our ability to understand and exploit the multitude of CRISPR-Cas systems in nature. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Reactive inspection response of NRC Region III to potential technical deficiencies identified in recent Nuclear Air Cleaning Conference papers

    International Nuclear Information System (INIS)

    Gill, C.F.

    1987-01-01

    In order to effectively meet its responsibility to protect the public health and safety, the Nuclear Regulatory Commission (NRC) nuclear power plant licensing and inspection programs respond to potential technical deficiencies identified by conference and professional society meeting papers when deemed appropriate. The NRC staff's response mechanisms for such technical deficiencies include: generic letters, Bulletins, Information Notices, Standard Review Plan (NUREG-0800) revisions, docketed Final Safety Analysis Report (FSAR) questions, special studies, special (reactive) inspection, and inspection program revisions. This paper describes reactive inspection efforts by Region III in response to potential technical deficiencies identified in recent air cleaning conference papers, including: post-accident effluent sample line deposition losses; failure to implement good engineering practices in the design, construction, and testing of Nuclear Air Treatment Systems (NATS); filter bypass via filter housing drain lines; spinster carbon degradation; use of silicone sealants and other temporary patching material in NATS; filter housing fire protection deluge system problems; lack of charcoal batch traceability; Quality Assurance records problems involving equipment, vendor, filter, and personnel qualifications; inadequate ANSI/ASME N510 acceptance criteria and tests; and failure to adequately demonstrate control room habitability per 10 CFR 50, Appendix A, General Design Criterion-19. Region III inspections indicate that many of these deficiencies appear to be prevalent. Inspection findings and utility responses to the findings are discussed. NRC Region III and Headquarters programmatic reactions to the identified generic problem areas are also discussed

  15. Identifying ADHD children using hemodynamic responses during a working memory task measured by functional near-infrared spectroscopy

    Science.gov (United States)

    Gu, Yue; Miao, Shuo; Han, Junxia; Liang, Zhenhu; Ouyang, Gaoxiang; Yang, Jian; Li, Xiaoli

    2018-06-01

    Objective. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting children and adults. Previous studies found that functional near-infrared spectroscopy (fNIRS) can reveal significant group differences in several brain regions between ADHD children and healthy controls during working memory tasks. This study aimed to use fNIRS activation patterns to identify ADHD children from healthy controls. Approach. FNIRS signals from 25 ADHD children and 25 healthy controls performing the n-back task were recorded; then, multivariate pattern analysis was used to discriminate ADHD individuals from healthy controls, and classification performance was evaluated for significance by the permutation test. Main results. The results showed that 86.0% (pADHD children from healthy controls based on fNIRS signals, which argues for the potential utility of fNIRS in future assessments.

  16. Identifying active surface phases for metal oxide electrocatalysts: a study of manganese oxide bi-functional catalysts for oxygen reduction and water oxidation catalysis

    DEFF Research Database (Denmark)

    Su, Hai-Yan; Gorlin, Yelena; Man, Isabela Costinela

    2012-01-01

    Progress in the field of electrocatalysis is often hampered by the difficulty in identifying the active site on an electrode surface. Herein we combine theoretical analysis and electrochemical methods to identify the active surfaces in a manganese oxide bi-functional catalyst for the oxygen...... reduction reaction (ORR) and the oxygen evolution reaction (OER). First, we electrochemically characterize the nanostructured α-Mn2O3 and find that it undergoes oxidation in two potential regions: initially, between 0.5 V and 0.8 V, a potential region relevant to the ORR and, subsequently, between 0.8 V...

  17. "Mature Regionalism" and the Genesis of "Functional Projects": "Educational Regionalism" in Small (and Micro-States)

    Science.gov (United States)

    Jules, Tavis D.

    2017-01-01

    This article advances that the movement towards "deeper" Caribbean integration has generated a shift from "immature" regionalism to a "mature" form of regionalism. Thus, mature regionalism, a new governance mechanism, in regulating the institutional and legal framework of Caribbean Single Market and Economy is…

  18. A new approach to assess COPD by identifying lung function break-points

    Directory of Open Access Journals (Sweden)

    Eriksson G

    2015-10-01

    Full Text Available Göran Eriksson,1,* Linnea Jarenbäck,1,* Stefan Peterson,2 Jaro Ankerst,1 Leif Bjermer,1 Ellen Tufvesson11Respiratory Medicine and Allergology, Department of Clinical Sciences, Lund University, 2Regional Cancer Center South, Skåne University Hospital, Lund, Sweden*These authors contributed equally to this workPurpose: COPD is a progressive disease, which can take different routes, leading to great heterogeneity. The aim of the post-hoc analysis reported here was to perform continuous analyses of advanced lung function measurements, using linear and nonlinear regressions.Patients and methods: Fifty-one COPD patients with mild to very severe disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stages I–IV and 41 healthy smokers were investigated post-bronchodilation by flow-volume spirometry, body plethysmography, diffusion capacity testing, and impulse oscillometry. The relationship between COPD severity, based on forced expiratory volume in 1 second (FEV1, and different lung function parameters was analyzed by flexible nonparametric method, linear regression, and segmented linear regression with break-points.Results: Most lung function parameters were nonlinear in relation to spirometric severity. Parameters related to volume (residual volume, functional residual capacity, total lung capacity, diffusion capacity [diffusion capacity of the lung for carbon monoxide], diffusion capacity of the lung for carbon monoxide/alveolar volume and reactance (reactance area and reactance at 5Hz were segmented with break-points at 60%–70% of FEV1. FEV1/forced vital capacity (FVC and resonance frequency had break-points around 80% of FEV1, while many resistance parameters had break-points below 40%. The slopes in percent predicted differed; resistance at 5 Hz minus resistance at 20 Hz had a linear slope change of -5.3 per unit FEV1, while residual volume had no slope change above and -3.3 change per unit FEV1 below its break-point of 61

  19. Multiple 5' ends of human cytomegalovirus UL57 transcripts identify a complex, cycloheximide-resistant promoter region that activates oriLyt

    International Nuclear Information System (INIS)

    Kiehl, Anita; Huang, Lili; Franchi, David; Anders, David G.

    2003-01-01

    The human cytomegalovirus (HCMV) UL57 gene lies adjacent to HCMV oriLyt, from which it is separated by an organizationally conserved, mostly noncoding region that is thought to both regulate UL57 expression and activate oriLyt function. However, the UL57 promoter has not been studied. We determined the 5' ends of UL57 transcripts toward an understanding of the potential relationship between UL57 expression and oriLyt activation. The results presented here identified three distinct 5' ends spread over 800 bp, at nt 90302, 90530, and 91138; use of these sites exhibited differential sensitivity to phosphonoformic acid treatment. Interestingly, a 10-kb UL57 transcript accumulated in cycloheximide-treated infected cells, even though other early transcripts were not detectable. However, the 10-kb transcript did not accumulate in cells treated with the more stringent translation inhibitor anisomycin. Consistent with the notion that the identified 5' ends arise from distinct transcription start sites, the sequences upstream of sites I and II functioned as promoters responsive to HCMV infection in transient assays. However, the origin-proximal promoter region III required downstream sequences for transcriptional activity. Mutation of candidate core promoter elements suggested that promoter III is regulated by an initiator region (Inr) and a downstream promoter element. Finally, a 42-bp sequence containing the candidate Inr activated a minimal oriLyt core construct in transient replication assays. Thus, these studies showed that a large, complex promoter region with novel features controls UL57 expression, and identified a sequence that regulates both UL57 transcription and oriLyt activation

  20. Identifying Tm-C82 isomers with density functional theory calculations

    International Nuclear Information System (INIS)

    Zheng Limin; He Hongqing; Yang Minghui; Zeng Qun; Yang Mingli

    2010-01-01

    Density functional theory calculations have been performed to study the geometrical and electronic properties of endohedral metallofullerene Tm-C 82 isomers. Three energetically favorable isomers (with C s , C 2 and C 2v symmetry, respectively) are identified which are consistent with the nuclear magnetic resonance (NMR) observations. The simulated ultraviolet photoelectron spectra (UPS) based on the three structures agree well with the measurements. Particularly, the parent cage of the experimentally observed Tm-C 82 isomer with C s symmetry is newly assigned, which matches the experiments better than early assignments. In addition, strong interaction between an endohedral Tm atom and the C 82 cage is discussed and is thought to be responsible for the dramatic change in the relative stability of C 82 isomers when Tm is encapsulated.

  1. Transformation Resistance in a Premature Aging Disorder Identifies a Tumor-Protective Function of BRD4

    Directory of Open Access Journals (Sweden)

    Patricia Fernandez

    2014-10-01

    Full Text Available Summary: Advanced age and DNA damage accumulation are prominent risk factors for cancer. The premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS provides a unique opportunity for studying the interplay between DNA damage and aging-associated tumor mechanisms, given that HGPS patients do not develop tumors despite elevated levels of DNA damage. Here, we have used HGPS patient cells to identify a protective mechanism to oncogenesis. We find that HGPS cells are resistant to neoplastic transformation. Resistance is mediated by the bromodomain protein BRD4, which exhibits altered genome-wide binding patterns in transformation-resistant cells, leading to inhibition of oncogenic dedifferentiation. BRD4 also inhibits, albeit to a lower extent, the tumorigenic potential of transformed cells from healthy individuals. BRD4-mediated tumor protection is clinically relevant given that a BRD4 gene signature predicts positive clinical outcome in breast and lung cancer. Our results demonstrate a protective function for BRD4 and suggest tissue-specific roles for BRD4 in tumorigenesis. : The premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS provides a unique tool for studying the interplay between DNA damage and aging-associated tumor mechanisms, given that HGPS patients do not develop tumors despite elevated levels of DNA damage. Using a genome-wide RNAi screen, Fernandez et al. now identify the bromodomain protein BRD4 as a mediator of the oncogenic resistance of HGPS cells. This tumor-protective function of BRD4 involves inhibition of oncogenic dedifferentiation and is also active in non-HGPS cells in a tissue-specific manner.

  2. Sensitivity of Ocean Reflectance Inversion Models for Identifying and Discriminating Between Phytoplankton Functional Groups

    Science.gov (United States)

    Werdell, P. Jeremy; Ooesler, Collin S.

    2012-01-01

    The daily, synoptic images provided by satellite ocean color instruments provide viable data streams for observing changes in the biogeochemistrY of marine ecosystems. Ocean reflectance inversion models (ORMs) provide a common mechanism for inverting the "color" of the water observed a satellite into marine inherent optical properties (lOPs) through a combination of empiricism and radiative transfer theory. lOPs, namely the spectral absorption and scattering characteristics of ocean water and its dissolved and particulate constituents, describe the contents of the upper ocean, information critical for furthering scientific understanding of biogeochemical oceanic processes. Many recent studies inferred marine particle sizes and discriminated between phytoplankton functional groups using remotely-sensed lOPs. While all demonstrated the viability of their approaches, few described the vertical distributions of the water column constituents under consideration and, thus, failed to report the biophysical conditions under which their model performed (e.g., the depth and thickness of the phytoplankton bloom(s)). We developed an ORM to remotely identifY Noctiluca miliaris and other phytoplankton functional types using satellite ocean color data records collected in the northern Arabian Sea. Here, we present results from analyses designed to evaluate the applicability and sensitivity of the ORM to varied biophysical conditions. Specifically, we: (1) synthesized a series of vertical profiles of spectral inherent optical properties that represent a wide variety of bio-optical conditions for the northern Arabian Sea under aN Miliaris bloom; (2) generated spectral remote-sensing reflectances from these profiles using Hydrolight; and, (3) applied the ORM to the synthesized reflectances to estimate the relative concentrations of diatoms and N Miliaris for each example. By comparing the estimates from the inversion model to those from synthesized vertical profiles, we were able to

  3. Identifying and quantifying main components of physiological noise in functional near infrared spectroscopy on prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Evgeniya eKirilina

    2013-12-01

    Full Text Available Functional Near-Infrared Spectroscopy (fNIRS is a promising method to study functional organization of the prefrontal cortex. However, in order to realize the high potential of fNIRS, effective discrimination between physiological noise originating from forehead skin haemodynamic and cerebral signals is required. Main sources of physiological noise are global and local blood flow regulation processes on multiple time scales. The goal of the present study was to identify the main physiological noise contributions in fNIRS forehead signals and to develop a method for physiological de-noising of fNIRS data. To achieve this goal we combined concurrent time-domain fNIRS and peripheral physiology recordings with wavelet coherence analysis. Depth selectivity was achieved by analyzing moments of photon time-of-flight distributions provided by time-domain fNIRS. Simultaneously, mean arterial blood pressure (MAP, heart rate (HR, and skin blood flow (SBF on the forehead were recorded. Wavelet coherence analysis was employed to quantify the impact of physiological processes on fNIRS signals separately for different time scales. We identified three main processes contributing to physiological noise in fNIRS signals on the forehead. The first process with the period of about 3 s is induced by respiration. The second process is highly correlated with time lagged MAP and HR fluctuations with a period of about 10 s often referred as Mayer waves. The third process is local regulation of the facial skin blood flow time locked to the task-evoked fNIRS signals. All processes affect oxygenated haemoglobin concentration more strongly than that of deoxygenated haemoglobin. Based on these results we developed a set of physiological regressors, which were used for physiological de-noising of fNIRS signals. Our results demonstrate that proposed de-noising method can significantly improve the sensitivity of fNIRS to cerebral signals.

  4. [A process of aquatic ecological function regionalization: The dual tree framework and conceptual model].

    Science.gov (United States)

    Guo, Shu Hai; Wu, Bo

    2017-12-01

    Aquatic ecological regionalization and aquatic ecological function regionalization are the basis of water environmental management of a river basin and rational utilization of an aquatic ecosystem, and have been studied in China for more than ten years. Regarding the common problems in this field, the relationship between aquatic ecological regionalization and aquatic ecological function regionalization was discussed in this study by systematic analysis of the aquatic ecological zoning and the types of aquatic ecological function. Based on the dual tree structure, we put forward the RFCH process and the diamond conceptual model. Taking Liaohe River basin as an example and referring to the results of existing regionalization studies, we classified the aquatic ecological function regions based on three-class aquatic ecological regionalization. This study provided a process framework for aquatic ecological function regionalization of a river basin.

  5. Mouse transgenesis identifies conserved functional enhancers and cis-regulatory motif in the vertebrate LIM homeobox gene Lhx2 locus.

    Directory of Open Access Journals (Sweden)

    Alison P Lee

    Full Text Available The vertebrate Lhx2 is a member of the LIM homeobox family of transcription factors. It is essential for the normal development of the forebrain, eye, olfactory system and liver as well for the differentiation of lymphoid cells. However, despite the highly restricted spatio-temporal expression pattern of Lhx2, nothing is known about its transcriptional regulation. In mammals and chicken, Crb2, Dennd1a and Lhx2 constitute a conserved linkage block, while the intervening Dennd1a is lost in the fugu Lhx2 locus. To identify functional enhancers of Lhx2, we predicted conserved noncoding elements (CNEs in the human, mouse and fugu Crb2-Lhx2 loci and assayed their function in transgenic mouse at E11.5. Four of the eight CNE constructs tested functioned as tissue-specific enhancers in specific regions of the central nervous system and the dorsal root ganglia (DRG, recapitulating partial and overlapping expression patterns of Lhx2 and Crb2 genes. There was considerable overlap in the expression domains of the CNEs, which suggests that the CNEs are either redundant enhancers or regulating different genes in the locus. Using a large set of CNEs (810 CNEs associated with transcription factor-encoding genes that express predominantly in the central nervous system, we predicted four over-represented 8-mer motifs that are likely to be associated with expression in the central nervous system. Mutation of one of them in a CNE that drove reporter expression in the neural tube and DRG abolished expression in both domains indicating that this motif is essential for expression in these domains. The failure of the four functional enhancers to recapitulate the complete expression pattern of Lhx2 at E11.5 indicates that there must be other Lhx2 enhancers that are either located outside the region investigated or divergent in mammals and fishes. Other approaches such as sequence comparison between multiple mammals are required to identify and characterize such enhancers.

  6. Modelling stream-fish functional traits in reference conditions: regional and local environmental correlates.

    Directory of Open Access Journals (Sweden)

    João M Oliveira

    Full Text Available Identifying the environmental gradients that control the functional structure of biological assemblages in reference conditions is fundamental to help river management and predict the consequences of anthropogenic stressors. Fish metrics (density of ecological guilds, and species richness from 117 least disturbed stream reaches in several western Iberia river basins were modelled with generalized linear models in order to investigate the importance of regional- and local-scale abiotic gradients to variation in functional structure of fish assemblages. Functional patterns were primarily associated with regional features, such as catchment elevation and slope, rainfall, and drainage area. Spatial variations of fish guilds were thus associated with broad geographic gradients, showing (1 pronounced latitudinal patterns, affected mainly by climatic factors and topography, or (2 at the basin level, strong upstream-downstream patterns related to stream position in the longitudinal gradient. Maximum native species richness was observed in midsize streams in accordance with the river continuum concept. The findings of our study emphasized the need to use a multi-scale approach in order to fully assess the factors that govern the functional organization of biotic assemblages in 'natural' streams, as well as to improve biomonitoring and restoration of fluvial ecosystems.

  7. Functional brain activation differences in stuttering identified with a rapid fMRI sequence

    Science.gov (United States)

    Kraft, Shelly Jo; Choo, Ai Leen; Sharma, Harish; Ambrose, Nicoline G.

    2011-01-01

    The purpose of this study was to investigate whether brain activity related to the presence of stuttering can be identified with rapid functional MRI (fMRI) sequences that involved overt and covert speech processing tasks. The long-term goal is to develop sensitive fMRI approaches with developmentally appropriate tasks to identify deviant speech motor and auditory brain activity in children who stutter closer to the age at which recovery from stuttering is documented. Rapid sequences may be preferred for individuals or populations who do not tolerate long scanning sessions. In this report, we document the application of a picture naming and phoneme monitoring task in three minute fMRI sequences with adults who stutter (AWS). If relevant brain differences are found in AWS with these approaches that conform to previous reports, then these approaches can be extended to younger populations. Pairwise contrasts of brain BOLD activity between AWS and normally fluent adults indicated the AWS showed higher BOLD activity in the right inferior frontal gyrus (IFG), right temporal lobe and sensorimotor cortices during picture naming and and higher activity in the right IFG during phoneme monitoring. The right lateralized pattern of BOLD activity together with higher activity in sensorimotor cortices is consistent with previous reports, which indicates rapid fMRI sequences can be considered for investigating stuttering in younger participants. PMID:22133409

  8. Nickel-resistance determinants in Acidiphilium sp. PM identified by genome-wide functional screening.

    Directory of Open Access Journals (Sweden)

    Patxi San Martin-Uriz

    Full Text Available Acidiphilium spp. are conspicuous dwellers of acidic, metal-rich environments. Indeed, they are among the most metal-resistant organisms; yet little is known about the mechanisms behind the metal tolerance in this genus. Acidiphilium sp. PM is an environmental isolate from Rio Tinto, an acidic, metal-laden river located in southwestern Spain. The characterization of its metal resistance revealed a remarkable ability to tolerate high Ni concentrations. Here we report the screening of a genomic library of Acidiphilium sp. PM to identify genes involved in Ni resistance. This approach revealed seven different genes conferring Ni resistance to E. coli, two of which form an operon encoding the ATP-dependent protease HslVU (ClpQY. This protease was found to enhance resistance to both Ni and Co in E. coli, a function not previously reported. Other Ni-resistance determinants include genes involved in lipopolysaccharide biosynthesis and the synthesis of branched amino acids. The diversity of molecular functions of the genes recovered in the screening suggests that Ni resistance in Acidiphilium sp. PM probably relies on different molecular mechanisms.

  9. Yeast functional screen to identify genes conferring salt stress tolerance in Salicornia europaea.

    Science.gov (United States)

    Nakahara, Yoshiki; Sawabe, Shogo; Kainuma, Kenta; Katsuhara, Maki; Shibasaka, Mineo; Suzuki, Masanori; Yamamoto, Kosuke; Oguri, Suguru; Sakamoto, Hikaru

    2015-01-01

    Salinity is a critical environmental factor that adversely affects crop productivity. Halophytes have evolved various mechanisms to adapt to saline environments. Salicornia europaea L. is one of the most salt-tolerant plant species. It does not have special salt-secreting structures like a salt gland or salt bladder, and is therefore a good model for studying the common mechanisms underlying plant salt tolerance. To identify candidate genes encoding key proteins in the mediation of salt tolerance in S. europaea, we performed a functional screen of a cDNA library in yeast. The library was screened for genes that allowed the yeast to grow in the presence of 1.3 M NaCl. We obtained three full-length S. europaea genes that confer salt tolerance. The genes are predicted to encode (1) a novel protein highly homologous to thaumatin-like proteins, (2) a novel coiled-coil protein of unknown function, and (3) a novel short peptide of 32 residues. Exogenous application of a synthetic peptide corresponding to the 32 residues improved salt tolerance of Arabidopsis. The approach described in this report provides a rapid assay system for large-scale screening of S. europaea genes involved in salt stress tolerance and supports the identification of genes responsible for such mechanisms. These genes may be useful candidates for improving crop salt tolerance by genetic transformation.

  10. RNAi-Based Functional Genomics Identifies New Virulence Determinants in Mucormycosis.

    Directory of Open Access Journals (Sweden)

    Trung Anh Trieu

    2017-01-01

    Full Text Available Mucorales are an emerging group of human pathogens that are responsible for the lethal disease mucormycosis. Unfortunately, functional studies on the genetic factors behind the virulence of these organisms are hampered by their limited genetic tractability, since they are reluctant to classical genetic tools like transposable elements or gene mapping. Here, we describe an RNAi-based functional genomic platform that allows the identification of new virulence factors through a forward genetic approach firstly described in Mucorales. This platform contains a whole-genome collection of Mucor circinelloides silenced transformants that presented a broad assortment of phenotypes related to the main physiological processes in fungi, including virulence, hyphae morphology, mycelial and yeast growth, carotenogenesis and asexual sporulation. Selection of transformants with reduced virulence allowed the identification of mcplD, which encodes a Phospholipase D, and mcmyo5, encoding a probably essential cargo transporter of the Myosin V family, as required for a fully virulent phenotype of M. circinelloides. Knock-out mutants for those genes showed reduced virulence in both Galleria mellonella and Mus musculus models, probably due to a delayed germination and polarized growth within macrophages. This study provides a robust approach to study virulence in Mucorales and as a proof of concept identified new virulence determinants in M. circinelloides that could represent promising targets for future antifungal therapies.

  11. Childhood executive function inventory (CHEXI): a promising measure for identifying young children with ADHD?

    Science.gov (United States)

    Thorell, Lisa B; Eninger, Lilianne; Brocki, Karin C; Bohlin, Gunilla

    2010-01-01

    The present study investigated whether the Childhood Executive Function Inventory (CHEXI) can discriminate between young children fulfilling the diagnostic criteria for attention-deficit/hyperactivity disorder (ADHD) and normally developing children. Unlike other executive function rating instruments, the CHEXI focuses specifically on inhibitory control and working memory, without including items that overlap with the diagnostic criteria of ADHD. The CHEXI was found to discriminate very well between children fulfilling the criteria for ADHD and normally developing children, also when controlling for the effect of IQ and socioeconomic status (SES). Both sensitivity and specificity of the two CHEXI subscales were shown to be high using either parent or teacher ratings. The highest overall classification rate was found for parent ratings on the inhibition subscale, with sensitivity and specificity reaching 93.3. To summarize, the CHEXI should be considered a promising measure for identifying young children with ADHD, although it is for future research to determine whether the CHEXI can be successfully used to also discriminate between different psychopathological groups.

  12. Yeast functional screen to identify genes conferring salt stress tolerance in Salicornia europaea

    Directory of Open Access Journals (Sweden)

    Yoshiki eNakahara

    2015-10-01

    Full Text Available Salinity is a critical environmental factor that adversely affects crop productivity. Halophytes have evolved various mechanisms to adapt to saline environments. Salicornia europaea L. is one of the most salt-tolerant plant species. It does not have special salt-secreting structures like a salt gland or salt bladder, and is therefore a good model for studying the common mechanisms underlying plant salt tolerance. To identify candidate genes encoding key proteins in the mediation of salt tolerance in S. europaea, we performed a functional screen of a cDNA library in yeast. The library was screened for genes that allowed the yeast to grow in the presence of 1.3 M NaCl. We obtained three full-length S. europaea genes that confer salt tolerance. The genes are predicted to encode (1 a novel protein highly homologous to thaumatin-like proteins, (2 a novel coiled-coil protein of unknown function, and (3 a novel short peptide of 32 residues. Exogenous application of a synthetic peptide corresponding to the 32 residues improved salt tolerance of Arabidopsis. The approach described in this report provides a rapid assay system for large-scale screening of S. europaea genes involved in salt stress tolerance and supports the identification of genes responsible for such mechanisms. These genes may be useful candidates for improving crop salt tolerance by genetic transformation.

  13. Functional profiling of microtumors to identify cancer associated fibroblast-derived drug targets.

    Science.gov (United States)

    Horman, Shane R; To, Jeremy; Lamb, John; Zoll, Jocelyn H; Leonetti, Nicole; Tu, Buu; Moran, Rita; Newlin, Robbin; Walker, John R; Orth, Anthony P

    2017-11-21

    Recent advances in chemotherapeutics highlight the importance of molecularly-targeted perturbagens. Although these therapies typically address dysregulated cancer cell proteins, there are increasing therapeutic modalities that take into consideration cancer cell-extrinsic factors. Targeting components of tumor stroma such as vascular or immune cells has been shown to represent an efficacious approach in cancer treatment. Cancer-associated fibroblasts (CAFs) exemplify an important stromal component that can be exploited in targeted therapeutics, though their employment in drug discovery campaigns has been relatively minimal due to technical logistics in assaying for CAF-tumor interactions. Here we report a 3-dimensional multi-culture tumor:CAF spheroid phenotypic screening platform that can be applied to high-content drug discovery initiatives. Using a functional genomics approach we systematically profiled 1,024 candidate genes for CAF-intrinsic anti-spheroid activity; identifying several CAF genes important for development and maintenance of tumor:CAF co-culture spheroids. Along with previously reported genes such as WNT, we identify CAF-derived targets such as ARAF and COL3A1 upon which the tumor compartment depends for spheroid development. Specifically, we highlight the G-protein-coupled receptor OGR1 as a unique CAF-specific protein that may represent an attractive drug target for treating colorectal cancer. In vivo , murine colon tumor implants in OGR1 knockout mice displayed delayed tumor growth compared to tumors implanted in wild type littermate controls. These findings demonstrate a robust microphysiological screening approach for identifying new CAF targets that may be applied to drug discovery efforts.

  14. Identifying group-sensitive physical activities: a differential item functioning analysis of NHANES data.

    Science.gov (United States)

    Gao, Yong; Zhu, Weimo

    2011-05-01

    The purpose of this study was to identify subgroup-sensitive physical activities (PA) using differential item functioning (DIF) analysis. A sub-unweighted sample of 1857 (men=923 and women=934) from the 2003-2004 National Health and Nutrition Examination Survey PA questionnaire data was used for the analyses. Using the Mantel-Haenszel, the simultaneous item bias test, and the ANOVA DIF methods, 33 specific leisure-time moderate and/or vigorous PA (MVPA) items were analyzed for DIF across race/ethnicity, gender, education, income, and age groups. Many leisure-time MVPA items were identified as large DIF items. When participating in the same amount of leisure-time MVPA, non-Hispanic blacks were more likely to participate in basketball and dance activities than non-Hispanic whites (NHW); NHW were more likely to participated in golf and hiking than non-Hispanic blacks; Hispanics were more likely to participate in dancing, hiking, and soccer than NHW, whereas NHW were more likely to engage in bicycling, golf, swimming, and walking than Hispanics; women were more likely to participate in aerobics, dancing, stretching, and walking than men, whereas men were more likely to engage in basketball, fishing, golf, running, soccer, weightlifting, and hunting than women; educated persons were more likely to participate in jogging and treadmill exercise than less educated persons; persons with higher incomes were more likely to engage in golf than those with lower incomes; and adults (20-59 yr) were more likely to participate in basketball, dancing, jogging, running, and weightlifting than older adults (60+ yr), whereas older adults were more likely to participate in walking and golf than younger adults. DIF methods are able to identify subgroup-sensitive PA and thus provide useful information to help design group-sensitive, targeted interventions for disadvantaged PA subgroups. © 2011 by the American College of Sports Medicine

  15. Identifying regions of strong scattering at the core-mantle boundary from analysis of PKKP precursor energy

    Science.gov (United States)

    Rost, S.; Earle, P.S.

    2010-01-01

    We detect seismic scattering from the core-mantle boundary related to the phase PKKP (PK. KP) in data from small aperture seismic arrays in India and Canada. The detection of these scattered waves in data from small aperture arrays is new and allows a better characterization of the fine-scale structure of the deep Earth especially in the southern hemisphere. Their slowness vector is determined from array processing allowing location of the heterogeneities at the core-mantle boundary using back-projection techniques through 1D Earth models. We identify strong scattering at the core-mantle boundary (CMB) beneath the Caribbean, Patagonia and the Antarctic Peninsula as well as beneath southern Africa. An analysis of the scattering regions relative to sources and receivers indicates that these regions represent areas of increased scattering likely due to increased heterogeneities close to the CMB. The 1. Hz array data used in this study is most sensitive to heterogeneity with scale lengths of about 10. km. Given the small size of the scatterers, a chemical origin of the heterogeneities is likely. By comparing the location of the fine-scale heterogeneity to geodynamical models and tomographic images, we identify different scattering mechanisms in regions related to subduction (Caribbean and Patagonia) and dense thermo chemical piles (Southern Africa). ?? 2010 Elsevier B.V.

  16. Identifying Functional Requirements for Flexible Airspace Management Concept Using Human-In-The-Loop Simulations

    Science.gov (United States)

    Lee, Paul U.; Bender, Kim; Pagan, Danielle

    2011-01-01

    Flexible Airspace Management (FAM) is a mid- term Next Generation Air Transportation System (NextGen) concept that allows dynamic changes to airspace configurations to meet the changes in the traffic demand. A series of human-in-the-loop (HITL) studies have identified procedures and decision support requirements needed to implement FAM. This paper outlines a suggested FAM procedure and associated decision support functionality based on these HITL studies. A description of both the tools used to support the HITLs and the planned NextGen technologies available in the mid-term are presented and compared. The mid-term implementation of several NextGen capabilities, specifically, upgrades to the Traffic Management Unit (TMU), the initial release of an en route automation system, the deployment of a digital data communication system, a more flexible voice communications network, and the introduction of a tool envisioned to manage and coordinate networked ground systems can support the implementation of the FAM concept. Because of the variability in the overall deployment schedule of the mid-term NextGen capabilities, the dependency of the individual NextGen capabilities are examined to determine their impact on a mid-term implementation of FAM. A cursory review of the different technologies suggests that new functionality slated for the new en route automation system is a critical enabling technology for FAM, as well as the functionality to manage and coordinate networked ground systems. Upgrades to the TMU are less critical but important nonetheless for FAM to be fully realized. Flexible voice communications network and digital data communication system could allow more flexible FAM operations but they are not as essential.

  17. An integrative -omics approach to identify functional sub-networks in human colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Rod K Nibbe

    2010-01-01

    Full Text Available Emerging evidence indicates that gene products implicated in human cancers often cluster together in "hot spots" in protein-protein interaction (PPI networks. Additionally, small sub-networks within PPI networks that demonstrate synergistic differential expression with respect to tumorigenic phenotypes were recently shown to be more accurate classifiers of disease progression when compared to single targets identified by traditional approaches. However, many of these studies rely exclusively on mRNA expression data, a useful but limited measure of cellular activity. Proteomic profiling experiments provide information at the post-translational level, yet they generally screen only a limited fraction of the proteome. Here, we demonstrate that integration of these complementary data sources with a "proteomics-first" approach can enhance the discovery of candidate sub-networks in cancer that are well-suited for mechanistic validation in disease. We propose that small changes in the mRNA expression of multiple genes in the neighborhood of a protein-hub can be synergistically associated with significant changes in the activity of that protein and its network neighbors. Further, we hypothesize that proteomic targets with significant fold change between phenotype and control may be used to "seed" a search for small PPI sub-networks that are functionally associated with these targets. To test this hypothesis, we select proteomic targets having significant expression changes in human colorectal cancer (CRC from two independent 2-D gel-based screens. Then, we use random walk based models of network crosstalk and develop novel reference models to identify sub-networks that are statistically significant in terms of their functional association with these proteomic targets. Subsequently, using an information-theoretic measure, we evaluate synergistic changes in the activity of identified sub-networks based on genome-wide screens of mRNA expression in CRC

  18. Determination of GMPE functional form for an active region with limited strong motion data: application to the Himalayan region

    Science.gov (United States)

    Bajaj, Ketan; Anbazhagan, P.

    2018-01-01

    Advancement in the seismic networks results in formulation of different functional forms for developing any new ground motion prediction equation (GMPE) for a region. Till date, various guidelines and tools are available for selecting a suitable GMPE for any seismic study area. However, these methods are efficient in quantifying the GMPE but not for determining a proper functional form and capturing the epistemic uncertainty associated with selection of GMPE. In this study, the compatibility of the recent available functional forms for the active region is tested for distance and magnitude scaling. Analysis is carried out by determining the residuals using the recorded and the predicted spectral acceleration values at different periods. Mixed effect regressions are performed on the calculated residuals for determining the intra- and interevent residuals. Additionally, spatial correlation is used in mixed effect regression by changing its likelihood function. Distance scaling and magnitude scaling are respectively examined by studying the trends of intraevent residuals with distance and the trend of the event term with magnitude. Further, these trends are statistically studied for a respective functional form of a ground motion. Additionally, genetic algorithm and Monte Carlo method are used respectively for calculating the hinge point and standard error for magnitude and distance scaling for a newly determined functional form. The whole procedure is applied and tested for the available strong motion data for the Himalayan region. The functional form used for testing are five Himalayan GMPEs, five GMPEs developed under NGA-West 2 project, two from Pan-European, and one from Japan region. It is observed that bilinear functional form with magnitude and distance hinged at 6.5 M w and 300 km respectively is suitable for the Himalayan region. Finally, a new regression coefficient for peak ground acceleration for a suitable functional form that governs the attenuation

  19. Machine Learning Classification to Identify the Stage of Brain-Computer Interface Therapy for Stroke Rehabilitation Using Functional Connectivity

    Directory of Open Access Journals (Sweden)

    Rosaleena Mohanty

    2018-05-01

    Full Text Available Interventional therapy using brain-computer interface (BCI technology has shown promise in facilitating motor recovery in stroke survivors; however, the impact of this form of intervention on functional networks outside of the motor network specifically is not well-understood. Here, we investigated resting-state functional connectivity (rs-FC in stroke participants undergoing BCI therapy across stages, namely pre- and post-intervention, to identify discriminative functional changes using a machine learning classifier with the goal of categorizing participants into one of the two therapy stages. Twenty chronic stroke participants with persistent upper-extremity motor impairment received neuromodulatory training using a closed-loop neurofeedback BCI device, and rs-functional MRI (rs-fMRI scans were collected at four time points: pre-, mid-, post-, and 1 month post-therapy. To evaluate the peak effects of this intervention, rs-FC was analyzed from two specific stages, namely pre- and post-therapy. In total, 236 seeds spanning both motor and non-motor regions of the brain were computed at each stage. A univariate feature selection was applied to reduce the number of features followed by a principal component-based data transformation used by a linear binary support vector machine (SVM classifier to classify each participant into a therapy stage. The SVM classifier achieved a cross-validation accuracy of 92.5% using a leave-one-out method. Outside of the motor network, seeds from the fronto-parietal task control, default mode, subcortical, and visual networks emerged as important contributors to the classification. Furthermore, a higher number of functional changes were observed to be strengthening from the pre- to post-therapy stage than the ones weakening, both of which involved motor and non-motor regions of the brain. These findings may provide new evidence to support the potential clinical utility of BCI therapy as a form of stroke

  20. Complete re-sequencing of a 2Mb topological domain encompassing the FTO/IRXB genes identifies a novel obesity-associated region upstream of IRX5

    DEFF Research Database (Denmark)

    Hunt, Lilian E; Noyvert, Boris; Bhaw-Rosun, Leena

    2015-01-01

    BACKGROUND: Association studies have identified a number of loci that contribute to an increased body mass index (BMI), the strongest of which is in the first intron of the FTO gene on human chromosome 16q12.2. However, this region is both non-coding and under strong linkage disequilibrium, making...... it recalcitrant to functional interpretation. Furthermore, the FTO gene is located within a complex cis-regulatory landscape defined by a topologically associated domain that includes the IRXB gene cluster, a trio of developmental regulators. Consequently, at least three genes in this interval have been...... implicated in the aetiology of obesity. METHODS: Here, we sequence a 2 Mb region encompassing the FTO, RPGRIP1L and IRXB cluster genes in 284 individuals from a well-characterised study group of Danish men containing extremely overweight young adults and controls. We further replicate our findings both...

  1. Toward automatic regional analysis of pulmonary function using inspiration and expiration thoracic CT

    DEFF Research Database (Denmark)

    Murphy, Keelin; Pluim, Josien P. W.; Rikxoort, Eva M. van

    2012-01-01

    and its results; (b) verify that the quantitative, regional ventilation measurements acquired through CT are meaningful for pulmonary function analysis; (c) identify the most effective of the calculated measurements in predicting pulmonary function; and (d) demonstrate the potential of the system...... disorder). Lungs, fissures, airways, lobes, and vessels are automatically segmented in both scans and the expiration scan is registered with the inspiration scan using a fully automatic nonrigid registration algorithm. Segmentations and registrations are examined and scored by expert observers to analyze...... to have good correlation with spirometry results, with several having correlation coefficients, r, in the range of 0.85–0.90. The best performing kNN classifier succeeded in classifying 67% of subjects into the correct COPD GOLD stage, with a further 29% assigned to a class neighboring the correct one...

  2. Source analysis using regional empirical Green's functions: The 2008 Wells, Nevada, earthquake

    Science.gov (United States)

    Mendoza, C.; Hartzell, S.

    2009-01-01

    We invert three-component, regional broadband waveforms recorded for the 21 February 2008 Wells, Nevada, earthquake using a finite-fault methodology that prescribes subfault responses using eight MW∼4 aftershocks as empirical Green's functions (EGFs) distributed within a 20-km by 21.6-km fault area. The inversion identifies a seismic moment of 6.2 x 1024 dyne-cm (5.8 MW) with slip concentrated in a compact 6.5-km by 4-km region updip from the hypocenter. The peak slip within this localized area is 88 cm and the stress drop is 72 bars, which is higher than expected for Basin and Range normal faults in the western United States. The EGF approach yields excellent fits to the complex regional waveforms, accounting for strong variations in wave propagation and site effects. This suggests that the procedure is useful for studying moderate-size earthquakes with limited teleseismic or strong-motion data and for examining uncertainties in slip models obtained using theoretical Green's functions.

  3. Functional integration changes in regional brain glucose metabolism from childhood to adulthood.

    Science.gov (United States)

    Trotta, Nicola; Archambaud, Frédérique; Goldman, Serge; Baete, Kristof; Van Laere, Koen; Wens, Vincent; Van Bogaert, Patrick; Chiron, Catherine; De Tiège, Xavier

    2016-08-01

    The aim of this study was to investigate the age-related changes in resting-state neurometabolic connectivity from childhood to adulthood (6-50 years old). Fifty-four healthy adult subjects and twenty-three pseudo-healthy children underwent [(18) F]-fluorodeoxyglucose positron emission tomography at rest. Using statistical parametric mapping (SPM8), age and age squared were first used as covariate of interest to identify linear and non-linear age effects on the regional distribution of glucose metabolism throughout the brain. Then, by selecting voxels of interest (VOI) within the regions showing significant age-related metabolic changes, a psychophysiological interaction (PPI) analysis was used to search for age-induced changes in the contribution of VOIs to the metabolic activity in other brain areas. Significant linear or non-linear age-related changes in regional glucose metabolism were found in prefrontal cortices (DMPFC/ACC), cerebellar lobules, and thalamo-hippocampal areas bilaterally. Decreases were found in the contribution of thalamic, hippocampal, and cerebellar regions to DMPFC/ACC metabolic activity as well as in the contribution of hippocampi to preSMA and right IFG metabolic activities. Increases were found in the contribution of the right hippocampus to insular cortex and of the cerebellar lobule IX to superior parietal cortex metabolic activities. This study evidences significant linear or non-linear age-related changes in regional glucose metabolism of mesial prefrontal, thalamic, mesiotemporal, and cerebellar areas, associated with significant modifications in neurometabolic connectivity involving fronto-thalamic, fronto-hippocampal, and fronto-cerebellar networks. These changes in functional brain integration likely represent a metabolic correlate of age-dependent effects on sensory, motor, and high-level cognitive functional networks. Hum Brain Mapp 37:3017-3030, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Modal functions. Properties and application for simulation of subject regions

    International Nuclear Information System (INIS)

    Rudkevich, A.V.

    1988-01-01

    New type of information structures for simulation of undefined information in information retrieval systems is suggested. Main properties of modal functions have been proved. Algorithm of their applications for data retrieval is presented. 9 refs

  5. Identifying the default mode network structure using dynamic causal modeling on resting-state functional magnetic resonance imaging.

    Science.gov (United States)

    Di, Xin; Biswal, Bharat B

    2014-02-01

    The default mode network is part of the brain structure that shows higher neural activity and energy consumption when one is at rest. The key regions in the default mode network are highly interconnected as conveyed by both the white matter fiber tracing and the synchrony of resting-state functional magnetic resonance imaging signals. However, the causal information flow within the default mode network is still poorly understood. The current study used the dynamic causal modeling on a resting-state fMRI data set to identify the network structure underlying the default mode network. The endogenous brain fluctuations were explicitly modeled by Fourier series at the low frequency band of 0.01-0.08Hz, and those Fourier series were set as driving inputs of the DCM models. Model comparison procedures favored a model wherein the MPFC sends information to the PCC and the bilateral inferior parietal lobule sends information to both the PCC and MPFC. Further analyses provide evidence that the endogenous connectivity might be higher in the right hemisphere than in the left hemisphere. These data provided insight into the functions of each node in the DMN, and also validate the usage of DCM on resting-state fMRI data. © 2013.

  6. Identifying Country-Specific Cultures of Physics Education: A differential item functioning approach

    Science.gov (United States)

    Mesic, Vanes

    2012-11-01

    In international large-scale assessments of educational outcomes, student achievement is often represented by unidimensional constructs. This approach allows for drawing general conclusions about country rankings with respect to the given achievement measure, but it typically does not provide specific diagnostic information which is necessary for systematic comparisons and improvements of educational systems. Useful information could be obtained by exploring the differences in national profiles of student achievement between low-achieving and high-achieving countries. In this study, we aimed to identify the relative weaknesses and strengths of eighth graders' physics achievement in Bosnia and Herzegovina in comparison to the achievement of their peers from Slovenia. For this purpose, we ran a secondary analysis of Trends in International Mathematics and Science Study (TIMSS) 2007 data. The student sample consisted of 4,220 students from Bosnia and Herzegovina and 4,043 students from Slovenia. After analysing the cognitive demands of TIMSS 2007 physics items, the correspondent differential item functioning (DIF)/differential group functioning contrasts were estimated. Approximately 40% of items exhibited large DIF contrasts, indicating significant differences between cultures of physics education in Bosnia and Herzegovina and Slovenia. The relative strength of students from Bosnia and Herzegovina showed to be mainly associated with the topic area 'Electricity and magnetism'. Classes of items which required the knowledge of experimental method, counterintuitive thinking, proportional reasoning and/or the use of complex knowledge structures proved to be differentially easier for students from Slovenia. In the light of the presented results, the common practice of ranking countries with respect to universally established cognitive categories seems to be potentially misleading.

  7. In vivo mapping of the functional regions of the DEAD-box helicase Vasa

    Directory of Open Access Journals (Sweden)

    Mehrnoush Dehghani

    2015-03-01

    Full Text Available The maternally expressed Drosophila melanogaster DEAD-box helicase Vasa (Vas is necessary for many cellular and developmental processes, including specification of primordial germ cells (pole cells, posterior patterning of the embryo, piRNA-mediated repression of transposon-encoded mRNAs, translational activation of gurken (grk mRNA, and completion of oogenesis itself. Vas protein accumulates in the perinuclear nuage in nurse cells soon after their specification, and then at stage 10 Vas translocates to the posterior pole plasm of the oocyte. We produced a series of transgenic constructs encoding eGFP-Vas proteins carrying mutations affecting different regions of the protein, and analyzed in vivo which Vas functions each could support. We identified novel domains in the N- and C-terminal regions of the protein that are essential for localization, transposon repression, posterior patterning, and pole cell specification. One such functional region, the most C-terminal seven amino acids, is specific to Vas orthologues and is thus critical to distinguishing Vas from other closely related DEAD-box helicases. Surprisingly, we also found that many eGFP-Vas proteins carrying mutations that would be expected to abrogate DEAD-box helicase function localized to the nuage and posterior pole, and retained the capacity to support oogenesis, although they did not function in embryonic patterning, pole cell specification, grk activation, or transposon repression. We conclude from these experiments that Vas, a multifunctional protein, uses different domains and different molecular associations to carry out its various cellular and developmental roles.

  8. Identifying the Functional Requirements for an Arizona Astronomy Data Hub (AADH)

    Science.gov (United States)

    Stahlman, G.; Heidorn, P. B.

    2015-12-01

    Astronomy data represent a curation challenge for information managers, as well as for astronomers. Extracting knowledge from these heterogeneous and complex datasets is particularly complicated and requires both interdisciplinary and domain expertise to accomplish true curation, with an overall goal of facilitating reproducible science through discoverability and persistence. A group of researchers and professional staff at the University of Arizona held several meetings during the spring of 2015 about astronomy data and the role of the university in curation of that data. The group decided that it was critical to obtain a broader consensus on the needs of the community. With assistance from a Start for Success grant provided by the University of Arizona Office of Research and Discovery and funding from the American Astronomical Society (AAS), a workshop was held in early July 2015, with 28 participants plus 4 organizers in attendance. Representing University researchers as well as astronomical facilities and a scholarly society, the group verified that indeed there is a problem with the long-term curation of some astronomical data not associated with major facilities, and that a repository or "data hub" with the correct functionality could facilitate research and the preservation and use of astronomy data. The workshop members also identified a set of next steps, including the identification of possible data and metadata to be included in the Hub. The participants further helped to identify additional information that must be gathered before construction of the AADH could begin, including identifying significant datasets that do not currently have sufficient preservation and dissemination infrastructure, as well as some data associated with journal publications and the broader context of the data beyond that directly published in the journals. Workshop participants recommended that a set of grant proposal should be developed that ensures community buy-in and

  9. DNA methylation in the APOE genomic region is associated with cognitive function in African Americans.

    Science.gov (United States)

    Liu, Jiaxuan; Zhao, Wei; Ware, Erin B; Turner, Stephen T; Mosley, Thomas H; Smith, Jennifer A

    2018-05-08

    Genetic variations in apolipoprotein E (APOE) and proximal genes (PVRL2, TOMM40, and APOC1) are associated with cognitive function and dementia, particularly Alzheimer's disease. Epigenetic mechanisms such as DNA methylation play a central role in the regulation of gene expression. Recent studies have found evidence that DNA methylation may contribute to the pathogenesis of dementia, but its association with cognitive function in populations without dementia remains unclear. We assessed DNA methylation levels of 48 CpG sites in the APOE genomic region in peripheral blood leukocytes collected from 289 African Americans (mean age = 67 years) from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Using linear regression, we examined the relationship between methylation in the APOE genomic region and multiple cognitive measures including learning, memory, processing speed, concentration, language and global cognitive function. We identified eight CpG sites in three genes (PVRL2, TOMM40, and APOE) that showed an inverse association between methylation level and delayed recall, a measure of memory, after adjusting for age and sex (False Discovery Rate q-value accounting for known genetic predictors for cognition. Our findings highlight the important role of epigenetic mechanisms in influencing cognitive performance, and suggest that changes in blood methylation may be an early indicator of individuals at risk for dementia as well as potential targets for intervention in asymptomatic populations.

  10. Regional homogeneity and resting state functional connectivity: associations with exposure to early life stress.

    Science.gov (United States)

    Philip, Noah S; Kuras, Yuliya I; Valentine, Thomas R; Sweet, Lawrence H; Tyrka, Audrey R; Price, Lawrence H; Carpenter, Linda L

    2013-12-30

    Early life stress (ELS) confers risk for psychiatric illness. Previous literature suggests ELS is associated with decreased resting-state functional connectivity (rs-FC) in adulthood, but there are no studies of resting-state neuronal activity in this population. This study investigated whether ELS-exposed individuals demonstrate resting-state activity patterns similar to those found in PTSD. Twenty-seven adults (14 with at least moderate ELS), who were medication-free and without psychiatric or medical illness, underwent MRI scans during two 4-minute rest periods. Resting-state activity was examined using regional homogeneity (ReHo), which estimates regional activation patterns through indices of localized concordance. ReHo values were compared between groups, followed by rs-FC analyses utilizing ReHo-localized areas as seeds to identify other involved regions. Relative to controls, ELS subjects demonstrated diminished ReHo in the inferior parietal lobule (IPL) and superior temporal gyrus (STG). ReHo values were inversely correlated with ELS severity. Secondary analyses revealed decreased rs-FC between the IPL and right precuneus/posterior cingulate, left fusiform gyrus, cerebellum and caudate in ELS subjects. These findings indicate that ELS is associated with altered resting-state activity and connectivity in brain regions involved in trauma-related psychiatric disorders. Future studies are needed to evaluate whether these associations represent potential imaging biomarkers of stress exposure. Published by Elsevier Ireland Ltd.

  11. Salmonella Persistence in Tomatoes Requires a Distinct Set of Metabolic Functions Identified by Transposon Insertion Sequencing

    Science.gov (United States)

    Desai, Prerak; Porwollik, Steffen; Canals, Rocio; Perez, Daniel R.; Chu, Weiping; McClelland, Michael; Teplitski, Max

    2016-01-01

    ABSTRACT Human enteric pathogens, such as Salmonella spp. and verotoxigenic Escherichia coli, are increasingly recognized as causes of gastroenteritis outbreaks associated with the consumption of fruits and vegetables. Persistence in plants represents an important part of the life cycle of these pathogens. The identification of the full complement of Salmonella genes involved in the colonization of the model plant (tomato) was carried out using transposon insertion sequencing analysis. With this approach, 230,000 transposon insertions were screened in tomato pericarps to identify loci with reduction in fitness, followed by validation of the screen results using competition assays of the isogenic mutants against the wild type. A comparison with studies in animals revealed a distinct plant-associated set of genes, which only partially overlaps with the genes required to elicit disease in animals. De novo biosynthesis of amino acids was critical to persistence within tomatoes, while amino acid scavenging was prevalent in animal infections. Fitness reduction of the Salmonella amino acid synthesis mutants was generally more severe in the tomato rin mutant, which hyperaccumulates certain amino acids, suggesting that these nutrients remain unavailable to Salmonella spp. within plants. Salmonella lipopolysaccharide (LPS) was required for persistence in both animals and plants, exemplifying some shared pathogenesis-related mechanisms in animal and plant hosts. Similarly to phytopathogens, Salmonella spp. required biosynthesis of amino acids, LPS, and nucleotides to colonize tomatoes. Overall, however, it appears that while Salmonella shares some strategies with phytopathogens and taps into its animal virulence-related functions, colonization of tomatoes represents a distinct strategy, highlighting this pathogen's flexible metabolism. IMPORTANCE Outbreaks of gastroenteritis caused by human pathogens have been increasingly associated with foods of plant origin, with tomatoes

  12. Studying Regional Wave Source Time Functions Using the Empirical Green's Function Method: Application to Central Asia

    Science.gov (United States)

    Xie, J.; Schaff, D. P.; Chen, Y.; Schult, F.

    2013-12-01

    Reliably estimated source time functions (STFs) from high-frequency regional waveforms, such as Lg, Pn and Pg, provide important input for seismic source studies, explosion detection and discrimination, and minimization of parameter trade-off in attenuation studies. We have searched for candidate pairs of larger and small earthquakes in and around China that share the same focal mechanism but significantly differ in magnitudes, so that the empirical Green's function (EGF) method can be applied to study the STFs of the larger events. We conducted about a million deconvolutions using waveforms from 925 earthquakes, and screened the deconvolved traces to exclude those that are from event pairs that involved different mechanisms. Only 2,700 traces passed this screening and could be further analyzed using the EGF method. We have developed a series of codes for speeding up the final EGF analysis by implementing automations and user-graphic interface procedures. The codes have been fully tested with a subset of screened data and we are currently applying them to all the screened data. We will present a large number of deconvolved STFs retrieved using various phases (Lg, Pn, Sn and Pg and coda) with information on any directivities, any possible dependence of pulse durations on the wave types, on scaling relations for the pulse durations and event sizes, and on the estimated source static stress drops.

  13. Regional differences in prediction models of lung function in Germany

    Directory of Open Access Journals (Sweden)

    Schäper Christoph

    2010-04-01

    Full Text Available Abstract Background Little is known about the influencing potential of specific characteristics on lung function in different populations. The aim of this analysis was to determine whether lung function determinants differ between subpopulations within Germany and whether prediction equations developed for one subpopulation are also adequate for another subpopulation. Methods Within three studies (KORA C, SHIP-I, ECRHS-I in different areas of Germany 4059 adults performed lung function tests. The available data consisted of forced expiratory volume in one second, forced vital capacity and peak expiratory flow rate. For each study multivariate regression models were developed to predict lung function and Bland-Altman plots were established to evaluate the agreement between predicted and measured values. Results The final regression equations for FEV1 and FVC showed adjusted r-square values between 0.65 and 0.75, and for PEF they were between 0.46 and 0.61. In all studies gender, age, height and pack-years were significant determinants, each with a similar effect size. Regarding other predictors there were some, although not statistically significant, differences between the studies. Bland-Altman plots indicated that the regression models for each individual study adequately predict medium (i.e. normal but not extremely high or low lung function values in the whole study population. Conclusions Simple models with gender, age and height explain a substantial part of lung function variance whereas further determinants add less than 5% to the total explained r-squared, at least for FEV1 and FVC. Thus, for different adult subpopulations of Germany one simple model for each lung function measures is still sufficient.

  14. Regional structural differences across functionally parcellated Brodmann areas of human primary somatosensory cortex.

    Science.gov (United States)

    Sánchez-Panchuelo, Rosa-María; Besle, Julien; Mougin, Olivier; Gowland, Penny; Bowtell, Richard; Schluppeck, Denis; Francis, Susan

    2014-06-01

    Ultra-high-field (UHF) MRI is ideally suited for structural and functional imaging of the brain. High-resolution structural MRI can be used to map the anatomical boundaries between functional domains of the brain by identifying changes related to the pattern of myelination within cortical gray matter, opening up the possibility to study the relationship between functional domains and underlying structure in vivo. In a recent study, we demonstrated the correspondence between functional (based on retinotopic mapping) and structural (based on changes in T2(⁎)-weighted images linked to myelination) parcellations of the primary visual cortex (V1) in vivo at 7T (Sanchez-Panchuelo et al., 2012b). Here, we take advantage of the improved BOLD CNR and high spatial resolution achievable at 7T to study regional structural variations across the functionally defined areas within the primary somatosensory cortex (S1) in individual subjects. Using a traveling wave fMRI paradigm to map the internal somatotopic representation of the index, middle, and ring fingers in S1, we were able to identify multiple map reversals at the tip and base, corresponding to the boundaries between Brodmann areas 3a, 3b, 1 and 2. Based on high resolution structural MRI data acquired in the same subjects, we inspected these functionally-parcellated Brodmann areas for differences in cortical thickness and MR contrast measures (magnetization transfer ratio (MTR) and signal intensity in phase sensitive inversion recovery (PSIR) images) that are sensitive to myelination. Consistent area-related differences in cortical thickness and MTR/PSIR measurements were found across subjects. However these measures did not have sufficient sensitivity to allow definition of areal boundaries. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Resolving anatomical and functional structure in human brain organization: identifying mesoscale organization in weighted network representations.

    Science.gov (United States)

    Lohse, Christian; Bassett, Danielle S; Lim, Kelvin O; Carlson, Jean M

    2014-10-01

    Human brain anatomy and function display a combination of modular and hierarchical organization, suggesting the importance of both cohesive structures and variable resolutions in the facilitation of healthy cognitive processes. However, tools to simultaneously probe these features of brain architecture require further development. We propose and apply a set of methods to extract cohesive structures in network representations of brain connectivity using multi-resolution techniques. We employ a combination of soft thresholding, windowed thresholding, and resolution in community detection, that enable us to identify and isolate structures associated with different weights. One such mesoscale structure is bipartivity, which quantifies the extent to which the brain is divided into two partitions with high connectivity between partitions and low connectivity within partitions. A second, complementary mesoscale structure is modularity, which quantifies the extent to which the brain is divided into multiple communities with strong connectivity within each community and weak connectivity between communities. Our methods lead to multi-resolution curves of these network diagnostics over a range of spatial, geometric, and structural scales. For statistical comparison, we contrast our results with those obtained for several benchmark null models. Our work demonstrates that multi-resolution diagnostic curves capture complex organizational profiles in weighted graphs. We apply these methods to the identification of resolution-specific characteristics of healthy weighted graph architecture and altered connectivity profiles in psychiatric disease.

  16. Croatian Energy Policy as Function of Regional Development and Employment

    International Nuclear Information System (INIS)

    Potocnik, V.

    2006-01-01

    The Republic of Croatia has modest proven fossil fuels (oil and gas) reserves and relatively abundant renewable energy potential (wind, solar, biomass, geothermal, hydro), distributed mainly in less developed regions of Croatia. The Croatian energy system is excessively dependent on expensive oil and natural gas (80% of primary energy), compared to the European Union (61%), and the world average (58%). Approximately 60% of total energy is imported, which considerably contributes to the country's very high foreign trade deficit and foreign debt. Putting into focus of the Croatian energy policy the improvement of energy efficiency and implementation of renewable energies would significantly increase opportunities for mitigating rather wide regional development disparities and high unemployment rates, at the same time reducing energy import, foreign trade deficit and foreign debt, and contributing to energy security as a part of the national security.(author)

  17. Cholinergic modulation of the hippocampal region and memory function.

    Science.gov (United States)

    Haam, Juhee; Yakel, Jerrel L

    2017-08-01

    Acetylcholine (ACh) plays an important role in memory function and has been implicated in aging-related dementia, in which the impairment of hippocampus-dependent learning strongly manifests. Cholinergic neurons densely innervate the hippocampus, mediating the formation of episodic as well as semantic memory. Here, we will review recent findings on acetylcholine's modulation of memory function, with a particular focus on hippocampus-dependent learning, and the circuits involved. In addition, we will discuss the complexity of ACh actions in memory function to better understand the physiological role of ACh in memory. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms. © 2017 International Society for Neurochemistry.

  18. An experimental framework to identify community functional components driving ecosystem processes and services delivery

    Czech Academy of Sciences Publication Activity Database

    Dias, A. T. C.; Berg, M. P.; de Bello, Francesco; Oosten, A. R. V.; Bílá, Karolína; Morreti, M.

    2013-01-01

    Roč. 101, č. 1 (2013), s. 29-37 ISSN 0022-0477 R&D Projects: GA ČR GAP505/12/1296 Institutional support: RVO:67985939 ; RVO:67179843 Keywords : CWM * ecosystem functioning * ecosystem processes * ecosystem services * functional divergence * functional diversity * functional evenness * functional richness * mass ratio hypothesis * Rao index Subject RIV: EH - Ecology, Behaviour; EF - Botanics (BU-J) Impact factor: 5.694, year: 2013

  19. Multiple sclerosis impairs regional functional connectivity in the cerebellum

    DEFF Research Database (Denmark)

    Dogonowski, Anne-Marie; Andersen, Kasper Winther; Madsen, Kristoffer Hougaard

    2013-01-01

    in the cerebellum in MS. This might be caused by a functional disruption of cortico-ponto-cerebellar and spino-cerebellar inputs, since patients with higher lesion load in the left cerebellar peduncles showed a stronger reduction in cerebellar homogeneity. In patients, two clusters in the left posterior cerebellum...

  20. Signature of Nonstationarity in Precipitation Extremes over Urbanizing Regions in India Identified through a Multivariate Frequency Analyses

    Science.gov (United States)

    Singh, Jitendra; Hari, Vittal; Sharma, Tarul; Karmakar, Subhankar; Ghosh, Subimal

    2016-04-01

    The statistical assumption of stationarity in hydrologic extreme time/event series has been relied heavily in frequency analysis. However, due to the analytically perceivable impacts of climate change, urbanization and concomitant land use pattern, assumption of stationarity in hydrologic time series will draw erroneous results, which in turn may affect the policy and decision-making. Past studies provided sufficient evidences on changes in the characteristics of Indian monsoon precipitation extremes and further it has been attributed to climate change and urbanization, which shows need of nonstationary analysis on the Indian monsoon extremes. Therefore, a comprehensive multivariate nonstationary frequency analysis has been conducted for the entire India to identify the precipitation characteristics (intensity, duration and depth) responsible for significant nonstationarity in the Indian monsoon. We use 1o resolution of precipitation data for a period of 1901-2004, in a Generalized Additive Model for Location, Scale and Shape (GAMLSS) framework. A cluster of GAMLSS models has been developed by considering nonstationarity in different combinations of distribution parameters through different regression techniques, and the best-fit model is further applied for bivariate analysis. A population density data has been utilized to identify the urban, urbanizing and rural regions. The results showed significant differences in the stationary and nonstationary bivariate return periods for the urbanizing grids, when compared to urbanized and rural grids. A comprehensive multivariate analysis has also been conducted to identify the precipitation characteristics particularly responsible for imprinting signature of nonstationarity.

  1. Functional organization of the insula and inner perisylvian regions

    Science.gov (United States)

    Jezzini, Ahmad; Caruana, Fausto; Stoianov, Ivilin; Gallese, Vittorio; Rizzolatti, Giacomo

    2012-01-01

    In the last few years, the insula has been the focus of many brain-imaging studies, mostly devoted to clarify its role in emotions and social communication. Physiological data, however, on which one may ground these correlative findings are almost totally lacking. Here, we investigated the functional properties of the insular cortex in behaving monkeys using intracortical microstimulation. Behavioral responses and heart rate changes were recorded. The results showed that the insula is functionally formed by two main subdivisions: (i) a sensorimotor field occupying the caudal–dorsal portion of the insula and appearing as an extension of the parietal lobe; and (ii) a mosaic of orofacial motor programs located in the anterior and centroventral insula sector. These programs show a progressive shift from dorsally located nonemotional motor programs (ingestive activity) to ventral ones laden with emotional and communicative content. The relationship between ingestive and other behaviors is discussed in an evolutionary perspective. PMID:22647599

  2. A novel PET imaging protocol identifies seizure-induced regional overactivity of P-glycoprotein at the blood-brain barrier

    Science.gov (United States)

    Bankstahl, Jens P.; Bankstahl, Marion; Kuntner, Claudia; Stanek, Johann; Wanek, Thomas; Meier, Martin; Ding, Xiao-Qi; Müller, Markus; Langer, Oliver; Löscher, Wolfgang

    2013-01-01

    About one third of epilepsy patients are pharmacoresistant. Overexpression of P-glycoprotein and other multidrug transporters at the blood-brain barrier is thought to play an important role in drug-refractory epilepsy. Thus, quantification of regionally different P-glycoprotein activity in the brain in vivo is essential to identify P-glycoprotein overactivity as the relevant mechanism for drug-resistance in an individual patient. Using the radiolabeled P-glycoprotein substrate (R)-[11C]verapamil and different doses of co-administered tariquidar, which is an inhibitor of P-glycoprotein, we evaluated whether small-animal positron emission tomography (PET) can quantify regional changes in transporter function in the rat brain at baseline and 48 h after a pilocarpine-induced status epilepticus. P-glycoprotein expression was additionally quantified by immunohistochemistry. To reveal putative seizure-induced changes in blood-brain barrier integrity, we performed gadolinium-enhanced magnetic resonance scans on a 7.0 Tesla small-animal scanner. Before P-glycoprotein modulation, brain uptake of (R)-[11C]verapamil was low in all regions investigated in control and post-status epilepticus rats. After administration of 3 mg/kg tariquidar, which inhibits P-glycoprotein only partially, we observed increased regional differentiation in brain activity uptake in post-status epilepticus versus control rats, which diminished after maximal P-glycoprotein inhibition. Regional increases in the efflux rate constant k2, but not in distribution volume VT or influx rate constant K1, correlated significantly with increases in P-glycoprotein expression measured by immunohistochemistry. This imaging protocol proves to be suitable to detect seizure-induced regional changes in P-glycoprotein activity and is readily applicable to humans, with the aim to detect relevant mechanisms of pharmacoresistance in epilepsy in vivo. PMID:21677164

  3. Analysis of selected reservoirs functioning in the Wielkopolska region

    Directory of Open Access Journals (Sweden)

    Mariusz Sojka

    2017-12-01

    Full Text Available The paper presents the problems related to the functioning of reservoirs in the Wielkopolska province and suggests their possible solutions. The reservoirs chosen as examples include typical dam constructions with a single water body (Jeziorsko, Rydzyna, two water body objects with separated preliminary part (Stare Miasto, Kowalskie, Radzyny and lateral constructions (Pakosław, Jutrosin. The reservoirs were built in period from 1970 to 2014. They differ in construction, functions and water management rules. Analysis of the main problems related to the reservoir functioning is aimed at finding ways of improving the construction of new reservoirs that would satisfy increasingly stringent environmental and legal restrictions and the methods of water management in the reservoirs. On the basis of a questionnaire filled in by the reservoir operators, the main problem is water quality. Especially the huge inflow of biogenic compounds causes blooms of algae and overgrowth with riparian vegetation. Some difficulties are also related to management of the reservoirs of multi-purpose operation. It is difficult to take into account the requirements of environmental flow maintenance, flood protection, water supply for agriculture and water use for tourism and recreation and hydropower generation, etc.

  4. Reconstructing Regional Ionospheric Electron Density: A Combined Spherical Slepian Function and Empirical Orthogonal Function Approach

    Science.gov (United States)

    Farzaneh, Saeed; Forootan, Ehsan

    2018-03-01

    The computerized ionospheric tomography is a method for imaging the Earth's ionosphere using a sounding technique and computing the slant total electron content (STEC) values from data of the global positioning system (GPS). The most common approach for ionospheric tomography is the voxel-based model, in which (1) the ionosphere is divided into voxels, (2) the STEC is then measured along (many) satellite signal paths, and finally (3) an inversion procedure is applied to reconstruct the electron density distribution of the ionosphere. In this study, a computationally efficient approach is introduced, which improves the inversion procedure of step 3. Our proposed method combines the empirical orthogonal function and the spherical Slepian base functions to describe the vertical and horizontal distribution of electron density, respectively. Thus, it can be applied on regional and global case studies. Numerical application is demonstrated using the ground-based GPS data over South America. Our results are validated against ionospheric tomography obtained from the constellation observing system for meteorology, ionosphere, and climate (COSMIC) observations and the global ionosphere map estimated by international centers, as well as by comparison with STEC derived from independent GPS stations. Using the proposed approach, we find that while using 30 GPS measurements in South America, one can achieve comparable accuracy with those from COSMIC data within the reported accuracy (1 × 1011 el/cm3) of the product. Comparisons with real observations of two GPS stations indicate an absolute difference is less than 2 TECU (where 1 total electron content unit, TECU, is 1016 electrons/m2).

  5. Functional and effective whole brain connectivity using magnetoencephalography to identify monozygotic twin pairs

    NARCIS (Netherlands)

    Demuru, M.; Gouw, A.; Hillebrand, A.; Stam, C J; van Dijk, B W; Scheltens, P.; Tijms, B.M.; Konijnenberg, E.; ten Kate-Booij, M.J.; den Braber, A; Smit, D J A; Boomsma, D I; Visser, P J

    2017-01-01

    Resting-state functional connectivity patterns are highly stable over time within subjects. This suggests that such 'functional fingerprints' may have strong genetic component. We investigated whether the functional (FC) or effective (EC) connectivity patterns of one monozygotic twin could be used

  6. Newly identified CYP2C93 is a functional enzyme in rhesus monkey, but not in cynomolgus monkey.

    Directory of Open Access Journals (Sweden)

    Yasuhiro Uno

    Full Text Available Cynomolgus monkey and rhesus monkey are used in drug metabolism studies due to their evolutionary closeness and physiological resemblance to human. In cynomolgus monkey, we previously identified cytochrome P450 (P450 or CYP 2C76 that does not have a human ortholog and is partly responsible for species differences in drug metabolism between cynomolgus monkey and human. In this study, we report characterization of CYP2C93 cDNA newly identified in cynomolgus monkey and rhesus monkey. The CYP2C93 cDNA contained an open reading frame of 490 amino acids approximately 84-86% identical to human CYP2Cs. CYP2C93 was located in the genomic region, which corresponded to the intergenic region in the human genome, indicating that CYP2C93 does not correspond to any human genes. CYP2C93 mRNA was expressed predominantly in the liver among 10 tissues analyzed. The CYP2C93 proteins heterologously expressed in Escherichia coli metabolized human CYP2C substrates, diclofenac, flurbiprofen, paclitaxel, S-mephenytoin, and tolbutamide. In addition to a normal transcript (SV1, an aberrantly spliced transcript (SV2 lacking exon 2 was identified, which did not give rise to a functional protein due to frameshift and a premature termination codon. Mini gene assay revealed that the genetic variant IVS2-1G>T at the splice site of intron 1, at least partly, accounted for the exon-2 skipping; therefore, this genotype would influence CYP2C93-mediated drug metabolism. SV1 was expressed in 6 of 11 rhesus monkeys and 1 of 8 cynomolgus monkeys, but the SV1 in the cynomolgus monkey was nonfunctional due to a rare null genotype (c.102T>del. These results suggest that CYP2C93 can play roles as a drug-metabolizing enzyme in rhesus monkeys (not in cynomolgus monkeys, although its relative contribution to drug metabolism has yet to be validated.

  7. Identifying the driving forces of urban expansion and its environmental impact in Jakarta-Bandung mega urban region

    Science.gov (United States)

    Pravitasari, A. E.; Rustiadi, E.; Mulya, S. P.; Setiawan, Y.; Fuadina, L. N.; Murtadho, A.

    2018-05-01

    The socio-economic development in Jakarta-Bandung Mega Urban Region (JBMUR) caused the increasing of urban expansion and led to a variety of environmental damage such as uncontrolled land use conversion and raising anthropogenic disaster. The objectives of this study are: (1) to identify the driving forces of urban expansion that occurs on JBMUR and (2) to analyze the environmental quality decline on JBMUR by producing time series spatial distribution map and spatial autocorrelation of floods and landslide as the proxy of anthropogenic disaster. The driving forces of urban expansion in this study were identified by employing Geographically Weighted Regression (GWR) model using 6 (six) independent variables, namely: population density, percentage of agricultural land, distance to the center of capital city/municipality, percentage of household who works in agricultural sector, distance to the provincial road, and distance to the local road. The GWR results showed that local demographic, social and economic factors including distance to the road spatially affect urban expansion in JBMUR. The time series spatial distribution map of floods and landslide event showed the spatial cluster of anthropogenic disaster in some areas. Through Local Moran Index, we found that environmental damage in one location has a significant impact on the condition of its surrounding area.

  8. Identifying landscape features associated with Rift Valley fever virus transmission, Ferlo region, Senegal, using very high spatial resolution satellite imagery.

    Science.gov (United States)

    Soti, Valérie; Chevalier, Véronique; Maura, Jonathan; Bégué, Agnès; Lelong, Camille; Lancelot, Renaud; Thiongane, Yaya; Tran, Annelise

    2013-03-01

    Dynamics of most of vector-borne diseases are strongly linked to global and local environmental changes. Landscape changes are indicators of human activities or natural processes that are likely to modify the ecology of the diseases. Here, a landscape approach developed at a local scale is proposed for extracting mosquito favourable biotopes, and for testing ecological parameters when identifying risk areas of Rift Valley fever (RVF) transmission. The study was carried out around Barkedji village, Ferlo region, Senegal. In order to test whether pond characteristics may influence the density and the dispersal behaviour of RVF vectors, and thus the spatial variation in RVFV transmission, we used a very high spatial resolution remote sensing image (2.4 m resolution) provided by the Quickbird sensor to produce a detailed land-cover map of the study area. Based on knowledge of vector and disease ecology, seven landscape attributes were defined at the pond level and computed from the land-cover map. Then, the relationships between landscape attributes and RVF serologic incidence rates in small ruminants were analyzed through a beta-binomial regression. Finally, the best statistical model according to the Akaike Information Criterion corrected for small samples (AICC), was used to map areas at risk for RVF. Among the derived landscape variables, the vegetation density index (VDI) computed within a 500 m buffer around ponds was positively correlated with serologic incidence (premote sensing data for identifying environmental risk factors and mapping RVF risk areas at a local scale.

  9. The ear region of Latimeria chalumnae: functional and evolutionary implications.

    Science.gov (United States)

    Bernstein, Peter

    2003-01-01

    The anatomy of Latimeria chalumnae has figured prominently in discussions about tetrapod origins. While the gross anatomy of Latimeria is well documented, relatively little is known about its otic anatomy and ontogeny. To examine the inner ear and the otoccipital part of the cranium, a serial-sectioned juvenile coelacanth was studied in detail and a three-dimensional reconstruction was made. The ear of Latimeria shows a derived condition compared to other basal sarcopterygians in having a connection between left and right labyrinths. This canalis communicans is perilymphatic in nature and originates at the transition point of the saccule and the lagena deep in the inner ear, where a peculiar sense end organ can be found. In most gnathostomes the inner ears are clearly separated from each other. A connection occurs in some fishes, e.g. within the Ostariophysi. In the sarcopterygian lineage no connections between the inner ears are known except in the Actinistia. Some fossil actinistians show a posteriorly directed duct lying between the foramen magnum and the notochordal canal, similar to the condition in the ear of Latimeria, so this derived character complex probably developed early in actinistian history. Because some features of the inner ear of Latimeria have been described as having tetrapod affinities, the problem of hearing and the anatomy of the otical complex in the living coelacanth has been closely connected to the question of early tetrapod evolution. It was assumed in the past that the structure found in Latimeria could exemplify a transitional stage in otic evolution between the fishlike sarcopterygians and the first tetrapods in a functional or even phylogenetic way. Here the possibility is considered that the canalis communicans does not possess any auditory function but rather is involved in sensing pressure changes during movements involving the intracranial joint. Earlier hypotheses of a putative tympanic ear are refuted.

  10. Functional SNP associated with birth weight in independent populations identified with a permutation step added to GBLUP-GWAS

    Science.gov (United States)

    This study was conducted as an initial assessment of a newly available genotyping assay containing about 34,000 common SNP included on previous SNP chips, and 199,000 sequence variants predicted to affect gene function. Objectives were to identify functional variants associated with birth weight in...

  11. Functional Analysis Identified Habit Reversal Components for the Treatment of Motor Tics

    Science.gov (United States)

    Dufrene, Brad A.; Harpole, Lauren Lestremau; Sterling, Heather E.; Perry, Erin J.; Burton, Britney; Zoder-Martell, Kimberly

    2013-01-01

    This study included brief functional analyses and treatment for motor tics exhibited by two children with Tourette Syndrome. Brief functional analyses were conducted in an outpatient treatment center and results were used to develop individualized habit reversal procedures. Treatment data were collected in clinic for one child and in clinic and…

  12. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function

    NARCIS (Netherlands)

    D.B. Hancock (Dana); M. Eijgelsheim (Mark); J.B. Wilk (Jemma); S.A. Gharib (Sina); L.R. Loehr (Laura); K. Marciante (Kristin); N. Franceschini (Nora); Y.M.T.A. van Durme; T.H. Chen; R.G. Barr (Graham); M.B. Schabath (Matthew); D.J. Couper (David); G.G. Brusselle (Guy); B.M. Psaty (Bruce); P. Tikka-Kleemola (Päivi); J.I. Rotter (Jerome); A.G. Uitterlinden (André); A. Hofman (Albert); N.M. Punjabi (Naresh); F. Rivadeneira Ramirez (Fernando); A.C. Morrison (Alanna); P.L. Enright (Paul); K.E. North (Kari); S.R. Heckbert (Susan); T. Lumley (Thomas); B.H.Ch. Stricker (Bruno); G.T. O'Connor (George); S.J. London (Stephanie)

    2010-01-01

    textabstractSpirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV1) and

  13. Influences of Moisture Regimes and Functional Plant Types on Nutrient Cycling in Permafrost Regions

    Science.gov (United States)

    McCaully, R. E.; Arendt, C. A.; Newman, B. D.; Heikoop, J. M.; Wilson, C. J.; Sevanto, S.; Wales, N. A.; Wullschleger, S.

    2017-12-01

    In the permafrost-dominated Arctic, climatic feedbacks exist between permafrost, soil moisture, functional plant type and presence of nutrients. Functional plant types present within the Arctic regulate and respond to changes in hydrologic regimes and nutrient cycling. Specifically, alders are a member of the birch family that use root nodules to fix nitrogen, which is a limiting nutrient strongly linked to fertilizing Arctic ecosystems. Previous investigations in the Seward Peninsula, AK show elevated presence of nitrate within and downslope of alder patches in degraded permafrost systems, with concentrations an order of magnitude greater than that of nitrate measured above these patches. Further observations within these degraded permafrost systems are crucial to assess whether alders are drivers of, or merely respond to, nitrate fluxes. In addition to vegetative feedbacks with nitrate supply, previous studies have also linked low moisture content to high nitrate production. Within discontinuous permafrost regions, the absence of permafrost creates well-drained regions with unsaturated soils whereas the presence of permafrost limits vertical drainage of soil-pore water creating elevated soil moisture content, which likely corresponds to lower nitrate concentrations. We investigate these feedbacks further in the Seward Peninsula, AK, through research supported by the United States Department of Energy Next Generation Ecosystem Experiment (NGEE) - Arctic. Using soil moisture and thaw depth as proxies to determine the extent of permafrost degradation, we identify areas of discontinuous permafrost over a heterogeneous landscape and collect co-located soilwater chemistry samples to highlight the complex relationships that exist between alder patches, soil moisture regimes, the presence of permafrost and available nitrate supply. Understanding the role of nitrogen in degrading permafrost systems, in the context of both vegetation present and soil moisture, is crucial

  14. ISOLATED WOLF-RAYET STARS AND O SUPERGIANTS IN THE GALACTIC CENTER REGION IDENTIFIED VIA PASCHEN-α EXCESS

    International Nuclear Information System (INIS)

    Mauerhan, J. C.; Stolovy, S. R.; Cotera, A.; Dong, H.; Wang, Q. D.; Morris, M. R.; Lang, C.

    2010-01-01

    We report the discovery of 19 hot, evolved, massive stars near the Galactic center region (GCR). These objects were selected for spectroscopy owing to their detection as strong sources of Paschen-α (Pα) emission-line excess, following a narrowband imaging survey of the central 0. 0 65 x 0. 0 25 (l, b) around Sgr A* with the Hubble Space Telescope. Discoveries include six carbon-type (WC) and five nitrogen-type (WN) Wolf-Rayet stars, six O supergiants, and two B supergiants. Two of the O supergiants have X-ray counterparts having properties consistent with solitary O stars and colliding-wind binaries. The infrared photometry of 17 stars is consistent with the Galactic center distance, but 2 of them are located in the foreground. Several WC stars exhibit a relatively large infrared excess, which is possibly thermal emission from hot dust. Most of the stars appear scattered throughout the GCR, with no relation to the three known massive young clusters; several others lie near the Arches and Quintuplet clusters and may have originated within one of these systems. The results of this work bring the total sample of Wolf-Rayet (WR) stars in the GCR to 88. All sources of strong Pα excess have been identified in the area surveyed with HST, which implies that the sample of WN stars in this region is near completion, and is dominated by late (WNL) types. The current WC sample, although probably not complete, is almost exclusively dominated by late (WCL) types. The observed WR subtype distribution in the GCR is a reflection of the intrinsic rarity of early subtypes (WNE and WCE) in the inner Galaxy, an effect that is driven by metallicity.

  15. New Sequence Variants in HLA Class II/III Region Associated with Susceptibility to Knee Osteoarthritis Identified by Genome-Wide Association Study

    Science.gov (United States)

    Nakajima, Masahiro; Takahashi, Atsushi; Kou, Ikuyo; Rodriguez-Fontenla, Cristina; Gomez-Reino, Juan J.; Furuichi, Tatsuya; Dai, Jin; Sudo, Akihiro; Uchida, Atsumasa; Fukui, Naoshi; Kubo, Michiaki; Kamatani, Naoyuki; Tsunoda, Tatsuhiko; Malizos, Konstantinos N.; Tsezou, Aspasia; Gonzalez, Antonio; Nakamura, Yusuke; Ikegawa, Shiro

    2010-01-01

    Osteoarthritis (OA) is a common disease that has a definite genetic component. Only a few OA susceptibility genes that have definite functional evidence and replication of association have been reported, however. Through a genome-wide association study and a replication using a total of ∼4,800 Japanese subjects, we identified two single nucleotide polymorphisms (SNPs) (rs7775228 and rs10947262) associated with susceptibility to knee OA. The two SNPs were in a region containing HLA class II/III genes and their association reached genome-wide significance (combined P = 2.43×10−8 for rs7775228 and 6.73×10−8 for rs10947262). Our results suggest that immunologic mechanism is implicated in the etiology of OA. PMID:20305777

  16. Functional connectivity mapping of regions associated with self- and other-processing.

    Science.gov (United States)

    Murray, Ryan J; Debbané, Martin; Fox, Peter T; Bzdok, Danilo; Eickhoff, Simon B

    2015-04-01

    Neuroscience literature increasingly suggests a conceptual self composed of interacting neural regions, rather than independent local activations, yet such claims have yet to be investigated. We, thus, combined task-dependent meta-analytic connectivity modeling (MACM) with task-independent resting-state (RS) connectivity analysis to delineate the neural network of the self, across both states. Given psychological evidence implicating the self's interdependence on social information, we also delineated the neural network underlying conceptual other-processing. To elucidate the relation between the self-/other-networks and their function, we mined the MACM metadata to generate a cognitive-behavioral profile for an empirically identified region specific to conceptual self, the pregenual anterior cingulate (pACC), and conceptual other, posterior cingulate/precuneus (PCC/PC). Mining of 7,200 published, task-dependent, neuroimaging studies, using healthy human subjects, yielded 193 studies activating the self-related seed and were conjoined with RS connectivity analysis to delineate a differentiated self-network composed of the pACC (seed) and anterior insula, relative to other functional connectivity. Additionally, 106 studies activating the other-related seed were conjoined with RS connectivity analysis to delineate a differentiated other-network of PCC/PC (seed) and angular gyrus/temporoparietal junction, relative to self-functional connectivity. The self-network seed related to emotional conflict resolution and motivational processing, whereas the other-network seed related to socially oriented processing and contextual information integration. Notably, our findings revealed shared RS connectivity between ensuing self-/other-networks within the ventromedial prefrontal cortex and medial orbitofrontal cortex, suggesting self-updating via integration of self-relevant social information. We, therefore, present initial neurobiological evidence corroborating the increasing

  17. Gain-of-function assays in the axolotl (Ambystoma mexicanum) to identify signaling pathways that induce and regulate limb regeneration.

    Science.gov (United States)

    Lee, Jangwoo; Aguilar, Cristian; Gardiner, David

    2013-01-01

    The adult salamander has been studied as a model for regeneration of complex tissues for many decades. Only recently with the development of gain-of-function assays for regeneration, has it been possible to screen for and assay the function of the multitude of signaling factors that have been identified in studies of embryonic development and tumorigenesis. Given the conservation of function of these regulatory pathways controlling growth and pattern formation, it is now possible to use the functional assays in the salamander to test the ability of endogenous as well as small-molecule signaling factors to induce a regenerative response.

  18. Identifying individual- and population-level characteristics that influence rates of risky alcohol consumption in regional communities.

    Science.gov (United States)

    Breen, Courtney; Shakeshaft, Anthony; Sanson-Fisher, Rob; D'Este, Catherine; Mattick, Richard P; Gilmour, Stuart

    2014-02-01

    To examine the extent to which individual- and community- level characteristics account for differences in risky alcohol consumption. A cross-sectional postal survey of 2,977 randomly selected individuals from 20 regional communities in NSW, Australia. Individuals drinking at harmful levels on the AUDIT and for risk of harm in the short term and long-term were identified. Multi-level modelling of the correlates of risky alcohol consumption at the individual and community level was conducted. There were differences between communities in alcohol consumption patterns. Being male, unmarried and reporting worse health were significant individual-level correlates for drinking at levels for risk of harm in the long term. The number of GPs (+) and police (-) were significant community characteristics. Being younger (≤25), unmarried, Australian born and with a larger income was associated with drinking at levels for risk of harm in the short term and harmful drinking on the AUDIT. The number of hotels and clubs was positively associated with drinking at levels for risk of harm in the short term. Rates of risky drinking vary significantly between communities and both individual and community characteristics are significantly associated with risky alcohol consumption. A combination of individual- and population-level interventions, tailored to the risk profile of individual communities, is most likely to be optimally effective. © 2014 The Authors. ANZJPH © 2014 Public Health Association of Australia.

  19. Comprehensive evaluation of disease- and trait-specific enrichment for eight functional elements among GWAS-identified variants.

    Science.gov (United States)

    Markunas, Christina A; Johnson, Eric O; Hancock, Dana B

    2017-07-01

    Genome-wide association study (GWAS)-identified variants are enriched for functional elements. However, we have limited knowledge of how functional enrichment may differ by disease/trait and tissue type. We tested a broad set of eight functional elements for enrichment among GWAS-identified SNPs (p Enrichment analyses were conducted using logistic regression, with Bonferroni correction. Overall, a significant enrichment was observed for all functional elements, except sequence motifs. Missense SNPs showed the strongest magnitude of enrichment. eQTLs were the only functional element significantly enriched across all diseases/traits. Magnitudes of enrichment were generally similar across diseases/traits, where enrichment was statistically significant. Blood vs. brain tissue effects on enrichment were dependent on disease/trait and functional element (e.g., cardiovascular disease: eQTLs P TissueDifference  = 1.28 × 10 -6 vs. enhancers P TissueDifference  = 0.94). Identifying disease/trait-relevant functional elements and tissue types could provide new insight into the underlying biology, by guiding a priori GWAS analyses (e.g., brain enhancer elements for psychiatric disease) or facilitating post hoc interpretation.

  20. Integrating genetic, transcriptional, and functional analyses to identify 5 novel genes for atrial fibrillation

    DEFF Research Database (Denmark)

    Sinner, Moritz F; Tucker, Nathan R; Lunetta, Kathryn L

    2014-01-01

    BACKGROUND: Atrial fibrillation (AF) affects >30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood. METHODS AND RESULTS: To identify new AF-re...

  1. Identifying the European fossil fuel plumes in the atmosphere over the Northeast Atlantic Region through isotopic observations and numerical modelling

    DEFF Research Database (Denmark)

    Geels, C.; Christensen, J.H.; Hansen, A.W.

    2006-01-01

    Atmospheric transport, C-14. fossil fuel CO_2, numerical modeling, the north East Atlantic Region Udgivelsesdato: 18 August......Atmospheric transport, C-14. fossil fuel CO_2, numerical modeling, the north East Atlantic Region Udgivelsesdato: 18 August...

  2. Functional screening identifies miRNAs influencing apoptosis and proliferation in colorectal cancer

    DEFF Research Database (Denmark)

    Christensen, Lise Lotte; Holm, Anja; Rantala, Juha

    2014-01-01

    MicroRNAs (miRNAs) play a critical role in many biological processes and are aberrantly expressed in human cancers. Particular miRNAs function either as tumor suppressors or oncogenes and appear to have diagnostic and prognostic significance. Although numerous miRNAs are dys-regulated in colorect...

  3. Identifying environmental risk to male reproductive function by occupational sperm studies: logistics and design options.

    NARCIS (Netherlands)

    Bonde, J.P.; Giwercman, A.; Ernst, E.; Joffe, M.; Bisanti, L.; Hoorne M, van M.; Thonneau, P.; Zielhuis, G.; Kiss, P.; Abell, A.; Larsen, S.B.; Danscher, G.; Kolstad, H.

    1996-01-01

    Malfunction of the male reproductive system might be a sensitive marker of environmental hazards, the effects of which may extend beyond reproductive function. The testis is more vulnerable to heat and ionising radiation than any other organ of the body and several xenobiotics are known to disrupt

  4. Family Structure and Functions Identified by Persons Living with HIV/AIDS.

    Science.gov (United States)

    Wong-Wylie, Gina; Doherty-Poirier, Maryanne; Kieren, Dianne

    1999-01-01

    A study looked at the structural and functional aspects of family from the perspective of six people living with acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV). Results showing how HIV/AIDS affects all members of the sufferer's family have implications for family practitioners. (Author/JOW)

  5. Independent component analysis of high-resolution imaging data identifies distinct functional domains

    DEFF Research Database (Denmark)

    Reidl, Juergen; Starke, Jens; Omer, David

    2007-01-01

    be automatically detected. In the visual cortex orientation columns can be extracted. In all cases artifacts due to movement, heartbeat or respiration were separated from the functional signal by sICA and could be removed from the data set. sICA is therefore a powerful technique for data compression, unbiased...

  6. The database of chromosome imbalance regions and genes resided in lung cancer from Asian and Caucasian identified by array-comparative genomic hybridization

    Directory of Open Access Journals (Sweden)

    Lo Fang-Yi

    2012-06-01

    Full Text Available Abstract Background Cancer-related genes show racial differences. Therefore, identification and characterization of DNA copy number alteration regions in different racial groups helps to dissect the mechanism of tumorigenesis. Methods Array-comparative genomic hybridization (array-CGH was analyzed for DNA copy number profile in 40 Asian and 20 Caucasian lung cancer patients. Three methods including MetaCore analysis for disease and pathway correlations, concordance analysis between array-CGH database and the expression array database, and literature search for copy number variation genes were performed to select novel lung cancer candidate genes. Four candidate oncogenes were validated for DNA copy number and mRNA and protein expression by quantitative polymerase chain reaction (qPCR, chromogenic in situ hybridization (CISH, reverse transcriptase-qPCR (RT-qPCR, and immunohistochemistry (IHC in more patients. Results We identified 20 chromosomal imbalance regions harboring 459 genes for Caucasian and 17 regions containing 476 genes for Asian lung cancer patients. Seven common chromosomal imbalance regions harboring 117 genes, included gain on 3p13-14, 6p22.1, 9q21.13, 13q14.1, and 17p13.3; and loss on 3p22.2-22.3 and 13q13.3 were found both in Asian and Caucasian patients. Gene validation for four genes including ARHGAP19 (10q24.1 functioning in Rho activity control, FRAT2 (10q24.1 involved in Wnt signaling, PAFAH1B1 (17p13.3 functioning in motility control, and ZNF322A (6p22.1 involved in MAPK signaling was performed using qPCR and RT-qPCR. Mean gene dosage and mRNA expression level of the four candidate genes in tumor tissues were significantly higher than the corresponding normal tissues (PP=0.06. In addition, CISH analysis of patients indicated that copy number amplification indeed occurred for ARHGAP19 and ZNF322A genes in lung cancer patients. IHC analysis of paraffin blocks from Asian Caucasian patients demonstrated that the frequency of

  7. The database of chromosome imbalance regions and genes resided in lung cancer from Asian and Caucasian identified by array-comparative genomic hybridization

    International Nuclear Information System (INIS)

    Lo, Fang-Yi; Nandi, Suvobroto; Salgia, Ravi; Wang, Yi-Ching; Chang, Jer-Wei; Chang, I-Shou; Chen, Yann-Jang; Hsu, Han-Shui; Huang, Shiu-Feng Kathy; Tsai, Fang-Yu; Jiang, Shih Sheng; Kanteti, Rajani

    2012-01-01

    Cancer-related genes show racial differences. Therefore, identification and characterization of DNA copy number alteration regions in different racial groups helps to dissect the mechanism of tumorigenesis. Array-comparative genomic hybridization (array-CGH) was analyzed for DNA copy number profile in 40 Asian and 20 Caucasian lung cancer patients. Three methods including MetaCore analysis for disease and pathway correlations, concordance analysis between array-CGH database and the expression array database, and literature search for copy number variation genes were performed to select novel lung cancer candidate genes. Four candidate oncogenes were validated for DNA copy number and mRNA and protein expression by quantitative polymerase chain reaction (qPCR), chromogenic in situ hybridization (CISH), reverse transcriptase-qPCR (RT-qPCR), and immunohistochemistry (IHC) in more patients. We identified 20 chromosomal imbalance regions harboring 459 genes for Caucasian and 17 regions containing 476 genes for Asian lung cancer patients. Seven common chromosomal imbalance regions harboring 117 genes, included gain on 3p13-14, 6p22.1, 9q21.13, 13q14.1, and 17p13.3; and loss on 3p22.2-22.3 and 13q13.3 were found both in Asian and Caucasian patients. Gene validation for four genes including ARHGAP19 (10q24.1) functioning in Rho activity control, FRAT2 (10q24.1) involved in Wnt signaling, PAFAH1B1 (17p13.3) functioning in motility control, and ZNF322A (6p22.1) involved in MAPK signaling was performed using qPCR and RT-qPCR. Mean gene dosage and mRNA expression level of the four candidate genes in tumor tissues were significantly higher than the corresponding normal tissues (P<0.001~P=0.06). In addition, CISH analysis of patients indicated that copy number amplification indeed occurred for ARHGAP19 and ZNF322A genes in lung cancer patients. IHC analysis of paraffin blocks from Asian Caucasian patients demonstrated that the frequency of PAFAH1B1 protein overexpression was 68

  8. Comparing rainfall patterns between regions in Peninsular Malaysia via a functional data analysis technique

    Science.gov (United States)

    Suhaila, Jamaludin; Jemain, Abdul Aziz; Hamdan, Muhammad Fauzee; Wan Zin, Wan Zawiah

    2011-12-01

    SummaryNormally, rainfall data is collected on a daily, monthly or annual basis in the form of discrete observations. The aim of this study is to convert these rainfall values into a smooth curve or function which could be used to represent the continuous rainfall process at each region via a technique known as functional data analysis. Since rainfall data shows a periodic pattern in each region, the Fourier basis is introduced to capture these variations. Eleven basis functions with five harmonics are used to describe the unimodal rainfall pattern for stations in the East while five basis functions which represent two harmonics are needed to describe the rainfall pattern in the West. Based on the fitted smooth curve, the wet and dry periods as well as the maximum and minimum rainfall values could be determined. Different rainfall patterns are observed among the studied regions based on the smooth curve. Using the functional analysis of variance, the test results indicated that there exist significant differences in the functional means between each region. The largest differences in the functional means are found between the East and Northwest regions and these differences may probably be due to the effect of topography and, geographical location and are mostly influenced by the monsoons. Therefore, the same inputs or approaches might not be useful in modeling the hydrological process for different regions.

  9. Identification by functional MRI of human cerebral region activated by taste stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Kakimoto, Naoya [Osaka Univ. (Japan). Faculty of Dentistry

    2000-09-01

    The purpose of this study was the examination of possible imaging of the primary taste region of human cerebral cortex by functional MRI (fMRI). Subjects were 19-36 years old, healthy adult male and female volunteers given information concerning the purpose, significance and method of the study. MRI equipment was 1.5 T Signa Horizon (GE) with Head Coil. Images were processed by the software FuncTool on the Advantage Windows Workstation (GE). Taste stimulation was done by swab bearing the solution of 4% quinine hydrochloride, 20% sodium chloride or distilled water (control) or by dripping from the syringe of the solutions, 8% tartaric acid or 80% sugar. Preliminary examinations with the swab suggested the possibility of the identification. Further, with use of dripping apparatus, the taste active region was shown to be identified by fMRI and of which area tended to be larger in male than in female: a significant difference was seen for the quinine hydrochloride. As above, the method was suggested to be a diagnostic mean for the taste perception. (K.H.)

  10. Identification by functional MRI of human cerebral region activated by taste stimulation

    International Nuclear Information System (INIS)

    Kakimoto, Naoya

    2000-01-01

    The purpose of this study was the examination of possible imaging of the primary taste region of human cerebral cortex by functional MRI (fMRI). Subjects were 19-36 years old, healthy adult male and female volunteers given information concerning the purpose, significance and method of the study. MRI equipment was 1.5 T Signa Horizon (GE) with Head Coil. Images were processed by the software FuncTool on the Advantage Windows Workstation (GE). Taste stimulation was done by swab bearing the solution of 4% quinine hydrochloride, 20% sodium chloride or distilled water (control) or by dripping from the syringe of the solutions, 8% tartaric acid or 80% sugar. Preliminary examinations with the swab suggested the possibility of the identification. Further, with use of dripping apparatus, the taste active region was shown to be identified by fMRI and of which area tended to be larger in male than in female: a significant difference was seen for the quinine hydrochloride. As above, the method was suggested to be a diagnostic mean for the taste perception. (K.H.)

  11. Urban agglomerations in the function of regional integration of Serbia in South-Eastern Europe

    Directory of Open Access Journals (Sweden)

    Tošić Dragutin

    2005-01-01

    Full Text Available In this article is analyzed the importance of urban agglomerations in the regional organization of Serbian space at one side, and on the other side they are taken as carriers of the future integration of the Serbian urban system into the urban of the South-Eastern Europe (SEE. In the regional configuration of Serbia, more different forms of territorial impacts of urbanization, urban areas and urban regions. High level of urban centralization is formed under the influence of the population density and functions of the metropolitan area of Belgrade. The problems of unbalanced disposition of population growth and qualitative transformation of urban centers are stressed and analyzed. Based on the role in integration process in the SEE, the metropolitan region of Belgrade is pointed out as its principal carrier and the metropolitan region of Niš as its secondary carrier, as well as the urban centers of importance for the cross-border regional cooperation. As the most suitable instrument of internal regional integration the model of Functional Urban Regions (FURs or Functional Urban Areas (FUAs is proposed, and for external regional integration is proposed the model of Metropolitan European Growth Areas (MEGAs. The coherent short-term and long-term development strategies for Serbian towns and their regions seem absent.

  12. Functional Connectome Analysis of Dopamine Neuron Glutamatergic Connections in Forebrain Regions.

    Science.gov (United States)

    Mingote, Susana; Chuhma, Nao; Kusnoor, Sheila V; Field, Bianca; Deutch, Ariel Y; Rayport, Stephen

    2015-12-09

    In the ventral tegmental area (VTA), a subpopulation of dopamine neurons express vesicular glutamate transporter 2 and make glutamatergic connections to nucleus accumbens (NAc) and olfactory tubercle (OT) neurons. However, their glutamatergic connections across the forebrain have not been explored systematically. To visualize dopamine neuron forebrain projections and to enable photostimulation of their axons independent of transmitter status, we virally transfected VTA neurons with channelrhodopsin-2 fused to enhanced yellow fluorescent protein (ChR2-EYFP) and used DAT(IREScre) mice to restrict expression to dopamine neurons. ChR2-EYFP-expressing neurons almost invariably stained for tyrosine hydroxylase, identifying them as dopaminergic. Dopamine neuron axons visualized by ChR2-EYFP fluorescence projected most densely to the striatum, moderately to the amygdala and entorhinal cortex (ERC), sparsely to prefrontal and cingulate cortices, and rarely to the hippocampus. Guided by ChR2-EYFP fluorescence, we recorded systematically from putative principal neurons in target areas and determined the incidence and strength of glutamatergic connections by activating all dopamine neuron terminals impinging on recorded neurons with wide-field photostimulation. This revealed strong glutamatergic connections in the NAc, OT, and ERC; moderate strength connections in the central amygdala; and weak connections in the cingulate cortex. No glutamatergic connections were found in the dorsal striatum, hippocampus, basolateral amygdala, or prefrontal cortex. These results indicate that VTA dopamine neurons elicit widespread, but regionally distinct, glutamatergic signals in the forebrain and begin to define the dopamine neuron excitatory functional connectome. Dopamine neurons are important for the control of motivated behavior and are involved in the pathophysiology of several major neuropsychiatric disorders. Recent studies have shown that some ventral midbrain dopamine neurons are

  13. Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci

    DEFF Research Database (Denmark)

    Glubb, Dylan M; Johnatty, Sharon E; Quinn, Michael C J

    2017-01-01

    We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D...... and ZNF100 are targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12, the chromatin interaction of a putative regulatory element with the ZNF100 promoter region correlated with candidate outcome variants. At 1q22, putative regulatory elements enhanced MEF2D promoter activity...... and haplotypes containing candidate outcome variants modulated these effects. In a public dataset, MEF2D and ZNF100 expression were both associated with ovarian cancer progression-free or overall survival time. In an extended set of 6,162 epithelial ovarian cancer patients, we found that functional candidates...

  14. Identifying high-functioning dyslexics: is self-report of early reading problems enough?

    Science.gov (United States)

    Deacon, S Hélène; Cook, Kathryn; Parrila, Rauno

    2012-07-01

    We used a questionnaire to identify university students with self-reported difficulties in reading acquisition during elementary school (self-report; n=31). The performance of the self-report group on standardized measures of word and non-word reading and fluency, passage comprehension and reading rate, and phonological awareness was compared to that of two other groups of university students: one with a recent diagnosis (diagnosed; n=20) and one with no self-reported reading acquisition problems (comparison group; n=33). The comparison group outperformed both groups with a history of reading difficulties (self-report and diagnosed) on almost all measures. The self-report and diagnosed groups performed similarly on most tasks, with the exception of untimed reading comprehension (better performance for diagnosed) and reading rate (better performance for self-report). The two recruitment methods likely sample from the same underlying population but identify individuals with different adaptive strategies.

  15. A CONCISE PANEL OF BIOMARKERS IDENTIFIES NEUROCOGNITIVE FUNCTIONING CHANGES IN HIV-INFECTED INDIVIDUALS

    Science.gov (United States)

    Marcotte, Thomas D.; Deutsch, Reena; Michael, Benedict Daniel; Franklin, Donald; Cookson, Debra Rosario; Bharti, Ajay R.; Grant, Igor; Letendre, Scott L.

    2013-01-01

    Background Neurocognitive (NC) impairment (NCI) occurs commonly in people living with HIV. Despite substantial effort, no biomarkers have been sufficiently validated for diagnosis and prognosis of NCI in the clinic. The goal of this project was to identify diagnostic or prognostic biomarkers for NCI in a comprehensively characterized HIV cohort. Methods Multidisciplinary case review selected 98 HIV-infected individuals and categorized them into four NC groups using normative data: stably normal (SN), stably impaired (SI), worsening (Wo), or improving (Im). All subjects underwent comprehensive NC testing, phlebotomy, and lumbar puncture at two timepoints separated by a median of 6.2 months. Eight biomarkers were measured in CSF and blood by immunoassay. Results were analyzed using mixed model linear regression and staged recursive partitioning. Results At the first visit, subjects were mostly middle-aged (median 45) white (58%) men (84%) who had AIDS (70%). Of the 73% who took antiretroviral therapy (ART), 54% had HIV RNA levels below 50 c/mL in plasma. Mixed model linear regression identified that only MCP-1 in CSF was associated with neurocognitive change group. Recursive partitioning models aimed at diagnosis (i.e., correctly classifying neurocognitive status at the first visit) were complex and required most biomarkers to achieve misclassification limits. In contrast, prognostic models were more efficient. A combination of three biomarkers (sCD14, MCP-1, SDF-1α) correctly classified 82% of Wo and SN subjects, including 88% of SN subjects. A combination of two biomarkers (MCP-1, TNF-α) correctly classified 81% of Im and SI subjects, including 100% of SI subjects. Conclusions This analysis of well-characterized individuals identified concise panels of biomarkers associated with NC change. Across all analyses, the two most frequently identified biomarkers were sCD14 and MCP-1, indicators of monocyte/macrophage activation. While the panels differed depending on

  16. Regional variation in the structure and function of parrotfishes on Arabian reefs

    KAUST Repository

    Hoey, Andrew; Feary, David A.; Burt, John A.; Vaughan, Grace; Pratchett, Morgan S.; Berumen, Michael L.

    2015-01-01

    the southern Arabian Gulf, and as such rates of grazing and erosion were negligible. This regional variation in abundance and functional composition of parrotfishes appears to be related to local environmental conditions.

  17. Engineering and Functional Characterization of Fusion Genes Identifies Novel Oncogenic Drivers of Cancer. | Office of Cancer Genomics

    Science.gov (United States)

    Oncogenic gene fusions drive many human cancers, but tools to more quickly unravel their functional contributions are needed. Here we describe methodology permitting fusion gene construction for functional evaluation. Using this strategy, we engineered the known fusion oncogenes, BCR-ABL1, EML4-ALK, and ETV6-NTRK3, as well as 20 previously uncharacterized fusion genes identified in TCGA datasets.

  18. Spatial and Single-Cell Transcriptional Profiling Identifies Functionally Distinct Human Dermal Fibroblast Subpopulations.

    Science.gov (United States)

    Philippeos, Christina; Telerman, Stephanie B; Oulès, Bénédicte; Pisco, Angela O; Shaw, Tanya J; Elgueta, Raul; Lombardi, Giovanna; Driskell, Ryan R; Soldin, Mark; Lynch, Magnus D; Watt, Fiona M

    2018-04-01

    Previous studies have shown that mouse dermis is composed of functionally distinct fibroblast lineages. To explore the extent of fibroblast heterogeneity in human skin, we used a combination of comparative spatial transcriptional profiling of human and mouse dermis and single-cell transcriptional profiling of human dermal fibroblasts. We show that there are at least four distinct fibroblast populations in adult human skin, not all of which are spatially segregated. We define markers permitting their isolation and show that although marker expression is lost in culture, different fibroblast subpopulations retain distinct functionality in terms of Wnt signaling, responsiveness to IFN-γ, and ability to support human epidermal reconstitution when introduced into decellularized dermis. These findings suggest that ex vivo expansion or in vivo ablation of specific fibroblast subpopulations may have therapeutic applications in wound healing and diseases characterized by excessive fibrosis. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Expansion of the Kano model to identify relevant customer segments and functional requirements

    DEFF Research Database (Denmark)

    Atlason, Reynir Smari; Stefansson, Arnaldur Smari; Wietz, Miriam

    2017-01-01

    The Kano model of customer satisfaction has been widely used to analyse perceived needs of customers. The model provides product developers valuable information about if, and then how much a given functional requirement (FR) will impact customer satisfaction if implemented within a product, system...... or a service. A current limitation of the Kano model is that it does not allow developers to visualise which combined sets of FRs would provide the highest satisfaction between different customer segments. In this paper, a stepwise method to address this particular shortcoming is presented. First......, a traditional Kano analysis is conducted for the different segments of interest. Second, for each FR, relationship functions are integrated between x=0 and x=1. Third, integrals are inserted into a combination matrix crossing segments and FRs, where FRs with the highest sum across the chosen segments...

  20. Functional MRI neurofeedback training on connectivity between two regions induces long-lasting changes in intrinsic functional network

    Directory of Open Access Journals (Sweden)

    Fukuda eMegumi

    2015-03-01

    Full Text Available Motor or perceptual learning is known to influence functional connectivity between brain regions and induce short-term changes in the intrinsic functional networks revealed as correlations in slow blood-oxygen-level dependent (BOLD signal fluctuations. However, no cause-and-effect relationship has been elucidated between a specific change in connectivity and a long-term change in global networks. Here, we examine the hypothesis that functional connectivity (i.e. temporal correlation between two regions is increased and preserved for a long time when two regions are simultaneously activated or deactivated. Using the connectivity-neurofeedback training paradigm, subjects successfully learned to increase the correlation of activity between the lateral parietal and primary motor areas, regions that belong to different intrinsic networks and negatively correlated before training under the resting conditions. Furthermore, whole-brain hypothesis-free analysis as well as functional network analyses demonstrated that the correlation in the resting state between these areas as well as the correlation between the intrinsic networks that include the areas increased for at least two months. These findings indicate that the connectivity-neurofeedback training can cause long-term changes in intrinsic connectivity and that intrinsic networks can be shaped by experience-driven modulation of regional correlation.

  1. Structural and functional analysis of APOA5 mutations identified in patients with severe hypertriglyceridemia[S

    Science.gov (United States)

    Mendoza-Barberá, Elena; Julve, Josep; Nilsson, Stefan K.; Lookene, Aivar; Martín-Campos, Jesús M.; Roig, Rosa; Lechuga-Sancho, Alfonso M.; Sloan, John H.; Fuentes-Prior, Pablo; Blanco-Vaca, Francisco

    2013-01-01

    During the diagnosis of three unrelated patients with severe hypertriglyceridemia, three APOA5 mutations [p.(Ser232_Leu235)del, p.Leu253Pro, and p.Asp332ValfsX4] were found without evidence of concomitant LPL, APOC2, or GPIHBP1 mutations. The molecular mechanisms by which APOA5 mutations result in severe hypertriglyceridemia remain poorly understood, and the functional impairment/s induced by these specific mutations was not obvious. Therefore, we performed a thorough structural and functional analysis that included follow-up of patients and their closest relatives, measurement of apoA-V serum concentrations, and sequencing of the APOA5 gene in 200 nonhyperlipidemic controls. Further, we cloned, overexpressed, and purified both wild-type and mutant apoA-V variants and characterized their capacity to activate LPL. The interactions of recombinant wild-type and mutated apoA-V variants with liposomes of different composition, heparin, LRP1, sortilin, and SorLA/LR11 were also analyzed. Finally, to explore the possible structural consequences of these mutations, we developed a three-dimensional model of full-length, lipid-free human apoA-V. A complex, wide array of impairments was found in each of the three mutants, suggesting that the specific residues affected are critical structural determinants for apoA-V function in lipoprotein metabolism and, therefore, that these APOA5 mutations are a direct cause of hypertriglyceridemia. PMID:23307945

  2. Some Risk Factors of Chronic Functional Constipation Identified in a Pediatric Population Sample from Romania

    Directory of Open Access Journals (Sweden)

    Claudia Olaru

    2016-01-01

    Full Text Available We conducted an observational study over a 1-year period, including 234 children aged 4–18 years and their caregivers and a matching control group. 60.73% of the children from the study group were males. Average age for the onset of constipation was 26.39 months. The frequency of defecation was 1/4.59 days (1/1.13 days in the control group. 38.49% of the patients in the sample group had a positive family history of functional constipation. The majority of children with functional constipation come from single-parent families, are raised by relatives, or come from orphanages. Constipated subjects had their last meal of the day at later hours and consumed fast foods more frequently than the children in the control sample. We found a statistically significant difference between groups regarding obesity/overweight and constipation (χ2=104.94,  df=2,  p<0.001 and regarding physical activity and constipation (χ2=18.419;  df=3;  p<0.001. There was a positive correlation between the number of hours spent watching television/using the computer and the occurrence of the disease (F = 92.162, p<0.001, and 95% Cl. Children from broken families, with positive family history, defective dietary habits, obesity and sedentary behavior, are at higher risk to develop chronic functional constipation.

  3. Structural equation modeling identifies markers of damage and function in the aging male Fischer 344 rat.

    Science.gov (United States)

    Grunz-Borgmann, Elizabeth A; Nichols, LaNita A; Wiedmeyer, Charles E; Spagnoli, Sean; Trzeciakowski, Jerome P; Parrish, Alan R

    2016-06-01

    The male Fischer 344 rat is an established model to study progressive renal dysfunction that is similar, but not identical, to chronic kidney disease (CKD) in humans. These studies were designed to assess age-dependent alterations in renal structure and function at late-life timepoints, 16-24 months. Elevations in BUN and plasma creatinine were not significant until 24 months, however, elevations in the more sensitive markers of function, plasma cystatin C and proteinuria, were detectable at 16 and 18 months, respectively. Interestingly, cystatin C levels were not corrected by caloric restriction. Urinary Kim-1, a marker of CKD, was elevated as early as 16 months. Klotho gene expression was significantly decreased at 24 months, but not at earlier timepoints. Alterations in renal structure, glomerulosclerosis and tubulointerstitial fibrosis, were noted at 16 months, with little change from 18 to 24 months. Tubulointerstitial inflammation was increased at 16 months, and remained similar from 18 to 24 months. A SEM (structural equation modeling) model of age-related renal dysfunction suggests that proteinuria is a marker of renal damage, while urinary Kim-1 is a marker of both damage and function. Taken together, these results demonstrate that age-dependent nephropathy begins as early as 16 months and progresses rapidly over the next 8 months. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Magnetic susceptibility to identify landscape segments on a detailed scale in the region of Jaboticabal, São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Mariana dos Reis Barrios

    2012-08-01

    Full Text Available The agricultural potential is generally assessed and managed based on a one-dimensional vision of the soil profile, however, the increased appreciation of sustainable production has stimulated studies on faster and more accurate evaluation techniques and methods of the agricultural potential on detailed scales. The objective of this study was to investigate the possibility of using soil magnetic susceptibility for the identification of landscape segments on a detailed scale in the region of Jaboticabal, São Paulo State. The studied area has two slope curvatures: linear and concave, subdivided into three landscape segments: upper slope (US, concave, middle slope (MS, linear and lower slope (LS, linear. In each of these segments, 20 points were randomly sampled from a database with 207 samples forming a regular grid installed in each landscape segment. The soil physical and chemical properties, CO2 emissions (FCO2 and magnetic susceptibility (MS of the samples were evaluated represented by: magnetic susceptibility of air-dried fine earth (MS ADFE, magnetic susceptibility of the total sand fraction (MS TS and magnetic susceptibility of the clay fraction (MS Cl in the 0.00 - 0.15 m layer. The principal component analysis showed that MS is an important property that can be used to identify landscape segments, because the correlation of this property within the first principal component was high. The hierarchical cluster analysis method identified two groups based on the variables selected by principal component analysis; of the six selected variables, three were related to magnetic susceptibility. The landscape segments were differentiated similarly by the principal component analysis and by the cluster analysis using only the properties with higher discriminatory power. The cluster analysis of MS ADFE, MS TS and MS Cl allowed the formation of three groups that agree with the segment division established in the field. The grouping by cluster

  5. Identifying environmental risk to male reproductive function by occupational sperm studies: logistics and design options.

    Science.gov (United States)

    Bonde, J P; Giwercman, A; Ernst, E

    1996-01-01

    Malfunction of the male reproductive system might be a sensitive marker of environmental hazards, the effects of which may extend beyond reproductive function. The testis is more vulnerable to heat and ionising radiation than any other organ of the body and several xenobiotics are known to disrupt spermatogenesis after low level exposure. Studies of environmental impact on human health are often most informative and accurate when carried out in the workplace where exposures can be high and easy to document. Semen analysis provides readily obtainable information on testicular function. The main advantages in comparison with functional measures such as fertility rates and time taken to conceive are the possibilities to examine men independently of marriage and pregnancy, to find changes of fecundity with different exposures within the same person and to detect adverse effects when no alteration of fertility is yet taking place. In the implementation of an occupational sperm study considerable attention must be paid to logistic issues. A mobile laboratory unit for initial semen preparation and processing may in some situations increase worker compliance and the quality of sperm cell motility. The cross sectional design which has been used in almost all male reproductive studies so far has several severe limitations including selection bias because of differential participation, difficulties in defining a suitable reference group, and lack of information about the time dimension of the cause-effect relation. The longitudinal design deals adequately with most of these constraints. Semen samples are collected before, during, and possibly after exposure to the risk factor of interest and causal inferences are based upon change of semen variables within a man over time rather than upon differences between men. The logistics of the longitudinal study may benefit from pre-employment health examinations to enrol newly hired workers and require fewer participants to obtain

  6. Budgetary Function Of Parliament In Implementing The Regional Budget Revenue And Expenditure

    Directory of Open Access Journals (Sweden)

    Idhamsyah

    2015-08-01

    Full Text Available The purpose of this research is to find and analyze the nature of budgetary functions by the House of Representatives. For find and analyze the implementation of budgetary functions by the Regional Representatives Council. The ideal model of future budgetary functions to achieve the objectives of the research methods of research conducted qualitatively analyze qualitative data were processed and analyzed with empirical normative approach regarding the existing problems of this writing. The results showed Regarding the implementation of the rights of the Budget as well as the limitation of the right budget is essentially located at the focus of the regional council to judge the legitimacy or expediency reasons of public towards the Regional Budget than technical assessment. Thus the Regional Representatives Council focusing on local budgetary strategy appropriate to peoples needs not on the technical budget figures. Implementation of budgetary function by the regional council where the implementation of the budget function must begin with the elaboration of various policies set out in the form of law in the form of work programs of government and development. As a suggestion from the author should importance of Central Sulawesi province put through coordination with regions that have implemented e-budgeting for the management of the Regional Budget of Central Sulawesi using e-budgeting system in order to manage the manufacturing budget.

  7. Regional variation in identified cancer care needs of early-career oncologists in China, India, and Pakistan.

    Science.gov (United States)

    Lyerly, H Kim; Fawzy, Maria R; Aziz, Zeba; Nair, Reena; Pramesh, C S; Parmar, Vani; Parikh, Purvish M; Jamal, Rozmin; Irumnaz, Azizunissa; Ren, Jun; Stockler, Martin R; Abernethy, Amy P

    2015-05-01

    Cancer incidence and mortality is increasing in the developing world. Inequities between low-, middle-, and high-income countries affect disease burden and the infrastructure needs in response to cancer. We surveyed early-career oncologists attending workshops in clinical research in three countries with emerging economies about their perception of the evolving cancer burden. A cross-sectional survey questionnaire was distributed at clinical trial concept development workshops held in Beijing, Lahore, Karachi, and Mumbai at major hospitals to acquire information regarding home-country health conditions and needs. A total of 100 respondents participated in the workshops held at major hospitals in the region (India = 29, China = 25, Pakistan = 42, and other = 4). Expected consensus on many issues (e.g., emergence of cancer as a significant health issue) was balanced with significant variation in priorities, opportunities, and challenges. Chinese respondents prioritized improvements in cancer-specific care and palliative care, Indian respondents favored improved cancer detection and advancing research in cancer care, and Pakistani respondents prioritized awareness of cancer and improvements in disease detection and cancer care research. For all, the most frequently cited opportunity was help in improving professional cancer education and training. Predominantly early-career oncologists attending clinical research workshops (in China, India, and Pakistan) identified needs for increasing clinical cancer research, professional education, and public awareness of cancer. Decision makers supporting efforts to reduce the burden of cancer worldwide will need to factor the specific needs and aspirations of health care providers in their country in prioritizing health policies and budgets. ©AlphaMed Press.

  8. NRC Information No. 91-29: Deficiencies identified during electrical distribution system functional inspections

    International Nuclear Information System (INIS)

    Rossi, C.E.

    1992-01-01

    During multidisciplinary inspections, the US Nuclear Regulatory Commission (NRC) has identified many deficiencies related to the electrical distribution system. To address these deficiencies, the NRC has developed an inspection to specifically evaluate the electrical distribution system. During the last year, the NRC completed eight EDSFIs, performing at least one in each of the several common deficiencies in the licensees' programs and in the electrical distribution systems as designed and configured at each plant. These deficiencies included inadequate ac voltages at the 480 Vac and 120 Vac distribution levels, inadequate procedures to test circuit breakers, and inadequate determinations and evaluations of setpoints

  9. Structural and functional characterization of Rpn12 identifies residues required for Rpn10 proteasome incorporation.

    Science.gov (United States)

    Boehringer, Jonas; Riedinger, Christiane; Paraskevopoulos, Konstantinos; Johnson, Eachan O D; Lowe, Edward D; Khoudian, Christina; Smith, Dominique; Noble, Martin E M; Gordon, Colin; Endicott, Jane A

    2012-11-15

    The ubiquitin-proteasome system targets selected proteins for degradation by the 26S proteasome. Rpn12 is an essential component of the 19S regulatory particle and plays a role in recruiting the extrinsic ubiquitin receptor Rpn10. In the present paper we report the crystal structure of Rpn12, a proteasomal PCI-domain-containing protein. The structure helps to define a core structural motif for the PCI domain and identifies potential sites through which Rpn12 might form protein-protein interactions. We demonstrate that mutating residues at one of these sites impairs Rpn12 binding to Rpn10 in vitro and reduces Rpn10 incorporation into proteasomes in vivo.

  10. Functional genomics identifies specific vulnerabilities in PTEN-deficient breast cancer.

    Science.gov (United States)

    Tang, Yew Chung; Ho, Szu-Chi; Tan, Elisabeth; Ng, Alvin Wei Tian; McPherson, John R; Goh, Germaine Yen Lin; Teh, Bin Tean; Bard, Frederic; Rozen, Steven G

    2018-03-22

    Phosphatase and tensin homolog (PTEN) is one of the most frequently inactivated tumor suppressors in breast cancer. While PTEN itself is not considered a druggable target, PTEN synthetic-sick or synthetic-lethal (PTEN-SSL) genes are potential drug targets in PTEN-deficient breast cancers. Therefore, with the aim of identifying potential targets for precision breast cancer therapy, we sought to discover PTEN-SSL genes present in a broad spectrum of breast cancers. To discover broad-spectrum PTEN-SSL genes in breast cancer, we used a multi-step approach that started with (1) a genome-wide short interfering RNA (siRNA) screen of ~ 21,000 genes in a pair of isogenic human mammary epithelial cell lines, followed by (2) a short hairpin RNA (shRNA) screen of ~ 1200 genes focused on hits from the first screen in a panel of 11 breast cancer cell lines; we then determined reproducibility of hits by (3) identification of overlaps between our results and reanalyzed data from 3 independent gene-essentiality screens, and finally, for selected candidate PTEN-SSL genes we (4) confirmed PTEN-SSL activity using either drug sensitivity experiments in a panel of 19 cell lines or mutual exclusivity analysis of publicly available pan-cancer somatic mutation data. The screens (steps 1 and 2) and the reproducibility analysis (step 3) identified six candidate broad-spectrum PTEN-SSL genes (PIK3CB, ADAMTS20, AP1M2, HMMR, STK11, and NUAK1). PIK3CB was previously identified as PTEN-SSL, while the other five genes represent novel PTEN-SSL candidates. Confirmation studies (step 4) provided additional evidence that NUAK1 and STK11 have PTEN-SSL patterns of activity. Consistent with PTEN-SSL status, inhibition of the NUAK1 protein kinase by the small molecule drug HTH-01-015 selectively impaired viability in multiple PTEN-deficient breast cancer cell lines, while mutations affecting STK11 and PTEN were largely mutually exclusive across large pan-cancer data sets. Six genes showed PTEN

  11. Evaluation of the functional activity of activated sludge from local waste water treatment plant in the Arctic region

    Directory of Open Access Journals (Sweden)

    Il'inskiy V. V.

    2017-03-01

    Full Text Available The paper considers characteristics of the activated sludge in the local wastewater treatment plant (LWTP and its ability to purify fully domestic sewage water in the Far North. Biochemical process of destruction of organic pollutants is influenced by a microbial complex functioning in aeration tanks. Taking into account climatic conditions of the region where the organic matter degradation processes are slowed, and lack of control over the operation, efficiency and occupational safety of LWTPs, it seems to be important to study the physiological characteristics of the bacteria used in bioremediation, and their ability to maximize the purifying domestic sewage in the Arctic region. Undue intervention in the biosphere systems leads to disruption of the balance of internal and external ecosystems communications. The goal of research is studying structural determination and functioning of activated sludge bacteriocenosis of LWTP TOPAS-5 (GK "Topol-ECO" in certain physical and chemical conditions of the habitat, and establishing completeness of cleaning process in this treatment plant. The paper considers the structure (quantitative and qualitative composition and function of LWTP activated sludge bacteriocenosis functioning in the Arctic region. The estimation of the activated sludge of full waste water treatment process of the LWTP has been given. The research's results have allowed to identify and determine the bacterial count of physiological groups of microorganisms purified domestic sewage; to isolate from activated sludge the bioflocculant-producing microorganisms' on the experimental medium; to evaluate efficiency of LWTP work in the Arctic region

  12. Functional characterization of MLH1 missense variants identified in Lynch Syndrome patients

    DEFF Research Database (Denmark)

    Andersen, Sofie Dabros; Liberti, Sascha Emilie; Lützen, Anne

    2012-01-01

    Germline mutations in the human DNA mismatch repair (MMR) genes MSH2 and MLH1 are associated with the inherited cancer disorder Lynch Syndrome (LS), also known as Hereditary Nonpolyposis Colorectal Cancer or HNPCC. A proportion of MSH2 and MLH1 mutations found in suspected LS patients give rise...... localization and protein-protein interaction with the dimer partner PMS2 and the MMR-associated exonuclease 1. We show that a significant proportion of examined variant proteins have functional defects in either subcellular localization or protein-protein interactions, which is suspected to lead to the cancer...

  13. Identifying an unknown function in a parabolic equation with overspecified data via He's variational iteration method

    International Nuclear Information System (INIS)

    Dehghan, Mehdi; Tatari, Mehdi

    2008-01-01

    In this research, the He's variational iteration technique is used for computing an unknown time-dependent parameter in an inverse quasilinear parabolic partial differential equation. Parabolic partial differential equations with overspecified data play a crucial role in applied mathematics and physics, as they appear in various engineering models. The He's variational iteration method is an analytical procedure for finding solutions of differential equations, is based on the use of Lagrange multipliers for identification of an optimal value of a parameter in a functional. To show the efficiency of the new approach, several test problems are presented for one-, two- and three-dimensional cases

  14. An interactive algorithm for identifying multiattribute measurable value functions based on finite-order independence of structural difference

    International Nuclear Information System (INIS)

    Tamura, Hiroyuki; Hikita, Shiro

    1985-01-01

    In this paper, we develop an interactive algorithm for identifying multiattribute measurable value functions based on the concept of finite-order independence of structural difference. This concept includes Dyer and Sarin's weak difference independence as special cases. The algorithm developed is composed of four major parts: 1) formulation of the problem 2) assessment of normalized conditional value functions and structural difference functions 3) assessment of corner values 4) assessment of the order of independence of structural difference and selection of the model. A hypothetical numerical example of a trade-off analysis for siting a nuclear power plant is included. (author)

  15. Parameterization of Cherenkov Light Lateral Distribution Function as a Function of the Zenith Angle around the Knee Region

    OpenAIRE

    Abdulsttar, Marwah M.; Al-Rubaiee, A. A.; Ali, Abdul Halim Kh.

    2016-01-01

    Cherenkov light lateral distribution function (CLLDF) simulation was fulfilled using CORSIKA code for configurations of Tunka EAS array of different zenith angles. The parameterization of the CLLDF was carried out as a function of the distance from the shower core in extensive air showers (EAS) and zenith angle on the basis of the CORSIKA simulation of primary proton around the knee region with the energy 3.10^15 eV at different zenith angles. The parameterized CLLDF is verified in comparison...

  16. Identifying arsenic trioxide (ATO) functions in leukemia cells by using time series gene expression profiles.

    Science.gov (United States)

    Yang, Hong; Lin, Shan; Cui, Jingru

    2014-02-10

    Arsenic trioxide (ATO) is presently the most active single agent in the treatment of acute promyelocytic leukemia (APL). In order to explore the molecular mechanism of ATO in leukemia cells with time series, we adopted bioinformatics strategy to analyze expression changing patterns and changes in transcription regulation modules of time series genes filtered from Gene Expression Omnibus database (GSE24946). We totally screened out 1847 time series genes for subsequent analysis. The KEGG (Kyoto encyclopedia of genes and genomes) pathways enrichment analysis of these genes showed that oxidative phosphorylation and ribosome were the top 2 significantly enriched pathways. STEM software was employed to compare changing patterns of gene expression with assigned 50 expression patterns. We screened out 7 significantly enriched patterns and 4 tendency charts of time series genes. The result of Gene Ontology showed that functions of times series genes mainly distributed in profiles 41, 40, 39 and 38. Seven genes with positive regulation of cell adhesion function were enriched in profile 40, and presented the same first increased model then decreased model as profile 40. The transcription module analysis showed that they mainly involved in oxidative phosphorylation pathway and ribosome pathway. Overall, our data summarized the gene expression changes in ATO treated K562-r cell lines with time and suggested that time series genes mainly regulated cell adhesive. Furthermore, our result may provide theoretical basis of molecular biology in treating acute promyelocytic leukemia. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. The polygenic risk for bipolar disorder influences brain regional function relating to visual and default state processing of emotional information.

    Science.gov (United States)

    Dima, Danai; de Jong, Simone; Breen, Gerome; Frangou, Sophia

    2016-01-01

    Genome-wise association studies have identified a number of common single-nucleotide polymorphisms (SNPs), each of small effect, associated with risk to bipolar disorder (BD). Several risk-conferring SNPs have been individually shown to influence regional brain activation thus linking genetic risk for BD to altered brain function. The current study examined whether the polygenic risk score method, which models the cumulative load of all known risk-conferring SNPs, may be useful in the identification of brain regions whose function may be related to the polygenic architecture of BD. We calculated the individual polygenic risk score for BD (PGR-BD) in forty-one patients with the disorder, twenty-five unaffected first-degree relatives and forty-six unrelated healthy controls using the most recent Psychiatric Genomics Consortium data. Functional magnetic resonance imaging was used to define task-related brain activation patterns in response to facial affect and working memory processing. We found significant effects of the PGR-BD score on task-related activation irrespective of diagnostic group. There was a negative association between the PGR-BD score and activation in the visual association cortex during facial affect processing. In contrast, the PGR-BD score was associated with failure to deactivate the ventromedial prefrontal region of the default mode network during working memory processing. These results are consistent with the threshold-liability model of BD, and demonstrate the usefulness of the PGR-BD score in identifying brain functional alternations associated with vulnerability to BD. Additionally, our findings suggest that the polygenic architecture of BD is not regionally confined but impacts on the task-dependent recruitment of multiple brain regions.

  18. Quantification of left ventricular regional functions using ECG-gated myocardial perfusion SPECT. Validation of left ventricular systolic functions

    International Nuclear Information System (INIS)

    Yamamoto, Akira; Takahashi, Naoto; Iwahara, Shin-ichiro; Munakata, Kazuo; Hosoya, Tetsuo

    2006-01-01

    We have developed a program to quantify regional left ventricular (LV) function and wall motion synchrony using electrocardiogram (ECG)-gated myocardial perfusion SPECT (MPS). This preliminary study was undertaken to validate the use of this program for estimating regional LV systolic function. Patients were subjected to MPS by 99m Tc-sestamibi at rest. The study included 20 patients who were confirmed to have a low probability of coronary artery disease (LPG; low probability group), 19 heart disease patients who were examined by MPS and equilibrium radionuclide angiography (ERNA) (ERG; ERNA group), and 24 patients who were examined by MPS and 2-dimensional echocardiography (2DE) (2DEG; 2DE group). The values of the ejection fraction (EF) and peak ejection rate (PER) were estimated. The global functions evaluated by this program were compared with those obtained by ERNA in the ERG. For regional assessment, the reference values of the functional indices were obtained for 17 LV segments in LPG. The Z score, (reference average value of the segment-patient's value of the segment)/reference standard deviation of the segment, was used for the evaluation of regional functions; a score equal to or greater than 2 was defined as abnormal. Semiquantitative visual interpretation of 2DE was used as the standard to assess wall motion. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of these criteria and the relationship between 2DE grading and Z scoring were validated in 2DEG. The values of the global EF and PER evaluated by this program correlated with those determined by ERNA (r=0.76 and 0.58, respectively; p -10 ). The potential of this program to quantify the regional systolic function was validated. (author)

  19. Identifiability of altimetry-based rating curve parameters in function of river morphological parameters

    Science.gov (United States)

    Paris, Adrien; André Garambois, Pierre; Calmant, Stéphane; Paiva, Rodrigo; Walter, Collischonn; Santos da Silva, Joecila; Medeiros Moreira, Daniel; Bonnet, Marie-Paule; Seyler, Frédérique; Monnier, Jérôme

    2016-04-01

    Estimating river discharge for ungauged river reaches from satellite measurements is not straightforward given the nonlinearity of flow behavior with respect to measurable and non measurable hydraulic parameters. As a matter of facts, current satellite datasets do not give access to key parameters such as river bed topography and roughness. A unique set of almost one thousand altimetry-based rating curves was built by fit of ENVISAT and Jason-2 water stages with discharges obtained from the MGB-IPH rainfall-runoff model in the Amazon basin. These rated discharges were successfully validated towards simulated discharges (Ens = 0.70) and in-situ discharges (Ens = 0.71) and are not mission-dependent. The rating curve writes Q = a(Z-Z0)b*sqrt(S), with Z the water surface elevation and S its slope gained from satellite altimetry, a and b power law coefficient and exponent and Z0 the river bed elevation such as Q(Z0) = 0. For several river reaches in the Amazon basin where ADCP measurements are available, the Z0 values are fairly well validated with a relative error lower than 10%. The present contribution aims at relating the identifiability and the physical meaning of a, b and Z0given various hydraulic and geomorphologic conditions. Synthetic river bathymetries sampling a wide range of rivers and inflow discharges are used to perform twin experiments. A shallow water model is run for generating synthetic satellite observations, and then rating curve parameters are determined for each river section thanks to a MCMC algorithm. Thanks to twin experiments, it is shown that rating curve formulation with water surface slope, i.e. closer from Manning equation form, improves parameter identifiability. The compensation between parameters is limited, especially for reaches with little water surface variability. Rating curve parameters are analyzed for riffle and pools for small to large rivers, different river slopes and cross section shapes. It is shown that the river bed

  20. Can structural and functional characteristics be used to identify riparian zone width in southern Appalachian headwater catchments?

    Science.gov (United States)

    Barton Clinton; James Vose; Jennifer Knoepp; Katherine Elliott; Barbara Reynolds; Stanley Zarnock

    2010-01-01

    We characterized structural and functional attributes along hillslope gradients in headwater catchments. We endeavored to identify parameters that described significant transitions along the hillslope. On each of four catchments, we installed eight 50 m transects perpendicular to the stream. Structural attributes included woody and herbaceous vegetation; woody debris...

  1. An AICD-based functional screen to identify APP metabolism regulators

    Directory of Open Access Journals (Sweden)

    Lee Jeremy C

    2007-08-01

    Full Text Available Abstract Background A central event in Alzheimer's disease (AD is the regulated intramembraneous proteolysis of the β-amyloid precursor protein (APP, to generate the β-amyloid (Aβ peptide and the APP intracellular domain (AICD. Aβ is the major component of amyloid plaques and AICD displays transcriptional activation properties. We have taken advantage of AICD transactivation properties to develop a genetic screen to identify regulators of APP metabolism. This screen relies on an APP-Gal4 fusion protein, which upon normal proteolysis, produces AICD-Gal4. Production of AICD-Gal4 induces Gal4-UAS driven luciferase expression. Therefore, when regulators of APP metabolism are modulated, luciferase expression is altered. Results To validate this experimental approach we modulated α-, β-, and γ-secretase levels and activities. Changes in AICD-Gal4 levels as measured by Western blot analysis were strongly and significantly correlated to the observed changes in AICD-Gal4 mediated luciferase activity. To determine if a known regulator of APP trafficking/maturation and Presenilin1 endoproteolysis could be detected using the AICD-Gal4 mediated luciferase assay, we knocked-down Ubiquilin 1 and observed decreased luciferase activity. We confirmed that Ubiquilin 1 modulated AICD-Gal4 levels by Western blot analysis and also observed that Ubiquilin 1 modulated total APP levels, the ratio of mature to immature APP, as well as PS1 endoproteolysis. Conclusion Taken together, we have shown that this screen can identify known APP metabolism regulators that control proteolysis, intracellular trafficking, maturation and levels of APP and its proteolytic products. We demonstrate for the first time that Ubiquilin 1 regulates APP metabolism in the human neuroblastoma cell line, SH-SY5Y.

  2. Dietary Patterns Associated with Cognitive Function among the Older People in Underdeveloped Regions: Finding from the NCDFaC Study.

    Science.gov (United States)

    Yin, Zhaoxue; Chen, Jing; Zhang, Jian; Ren, Zeping; Dong, Kui; Kraus, Virginia B; Wang, Zhuoqun; Zhang, Mei; Zhai, Yi; Song, Pengkun; Zhao, Yanfang; Pang, Shaojie; Mi, Shengquan; Zhao, Wenhua

    2018-04-09

    Although dietary patterns are crucial to cognitive function, associations of dietary patterns with cognitive function have not yet been fully understood. This cross-sectional study explored dietary patterns associated with cognitive function among the older adults in underdeveloped regions, using 1504 community-dwelling older adults aged 60 and over. Diet was assessed using a food frequency questionnaire and 24-h dietary recall. Factor analysis was used to extract dietary patterns. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE). Two dietary patterns, a "mushroom, vegetable, and fruits" (MVF) pattern and a "meat and soybean products" (MS) pattern, were identified. The MVF pattern, characterized by high consumption of mushrooms, vegetables, and fruits was significantly positively associated with cognitive function ( p cognitive impairment and β (95% CIs) 0.15 (0.02, 0.29) for -log (31-MMSE score). The MS pattern, characterized by high consumption of soybean products and meat, was also associated with better cognitive function, with an odds ratio of 0.47 (95% CIs 0.30, 0.74) for cognitive impairment and β (95% CIs) 0.34 (0.21, 0.47) for -log (31-MMSE score). Our results suggested that both the MVF and MS patterns were positively associated with better cognitive function among older adults in underdeveloped regions.

  3. Functional characterization of a CRH missense mutation identified in an ADNFLE family.

    Directory of Open Access Journals (Sweden)

    Veronica Sansoni

    Full Text Available Nocturnal frontal lobe epilepsy has been historically considered a channelopathy caused by mutations in subunits of the neuronal nicotinic acetylcholine receptor or in a recently reported potassium channel. However, these mutations account for only a minority of patients, and the existence of at least a new locus for the disease has been demonstrated. In 2005, we detected two nucleotide variations in the promoter of the CRH gene coding for the corticotropin releasing hormone in 7 patients. These variations cosegregated with the disease and were demonstrated to alter the cellular levels of this hormone. Here, we report the identification in an Italian affected family of a novel missense mutation (hpreproCRH p.Pro30Arg located in the region of the CRH coding for the protein pro-sequence. The mutation was detected in heterozygosity in the two affected individuals. In vitro assays demonstrated that this mutation results in reduced levels of protein secretion in the short time thus suggesting that mutated people could present an altered capability to respond immediately to stress agents.

  4. Impaired insula functional connectivity associated with persistent pain perception in patients with complex regional pain syndrome

    Science.gov (United States)

    Jang, Joon Hwan; Lee, Do-Hyeong; Lee, Kyung-Jun; Lee, Won Joon; Moon, Jee Youn; Kim, Yong Chul

    2017-01-01

    Given that the insula plays a contributory role in the perception of chronic pain, we examined the resting-state functional connectivity between the insular cortex and other brain regions to investigate neural underpinnings of persisting perception of background pain in patients with complex regional pain syndrome (CRPS). A total of 25 patients with CRPS and 25 matched healthy controls underwent functional magnetic resonance imaging at rest. With the anterior and posterior insular cortices as seed regions, we compared the strength of the resting-state functional connectivity between the two groups. Functional connectivity between the anterior and posterior insular cortices and the postcentral and inferior frontal gyri, cingulate cortices was reduced in patients with CRPS compared with controls. Additionally, greater reductions in functional connectivity between the anterior insula and right postcentral gyrus were associated with more severe sensory pain in patients with CRPS (short-form McGill Pain Questionnaire sensory subscores, r = -.517, P = .023). The present results imply a possible role of the insula in aberrant processing of pain information in patients with CRPS. The findings suggest that a functional derangement of the connection between one of the somatosensory cortical functions of perception and one of the insular functions of awareness can play a significant role in the persistent experience of regional pain that is not confined to a specific nerve territory. PMID:28692702

  5. Functional MRI approach for assessing hemispheric predominance of regions activated by a phonological and a semantic task

    Energy Technology Data Exchange (ETDEWEB)

    Cousin, Emilie; Peyrin, Carole; Pichat, Cedric [Laboratoire de Psychologie et Neurocognition, UMR CNRS 5105, Universite Pierre Mendes-France, BP 47, 38040 Grenoble Cedex 09 (France); Lamalle, Laurent; Le Bas, Jean-Francois [Unite IRM, IFR1, CHU Grenoble (France); Baciu, Monica [Laboratoire de Psychologie et Neurocognition, UMR CNRS 5105, Universite Pierre Mendes-France, BP 47, 38040 Grenoble Cedex 09 (France)], E-mail: mbaciu@upmf-grenoble.fr

    2007-08-15

    This fMRI study performed in healthy subjects aimed at using a statistical approach in order to determine significant functional differences between hemispheres and to assess specialized regions activated during a phonological and during a semantic task. This approach ('flip' method and subsequent statistical analyses of the parameter estimates extracted from regions of interest) allows identifying: (a) hemispheric specialized regions for each language task [semantic (living categorization) and phonological (rhyme detection)] and (b) condition-specific regions with respect to paradigm conditions (task and control). Our results showed that the rhyme-specific task regions were the inferior frontal (sub-region of BA 44, 45) and left inferior parietal (BA 40, 39) lobules. Furthermore, within the inferior parietal lobule, the angular gyrus was specific to target (rhyming) items (related to successfully grapho-phonemic processing). The categorization-specific task regions were the left inferior frontal (sub-region of BA 44, 45) and superior temporal (BA 22) cortices. Furthermore, the superior temporal gyrus was related to non-target (non-living) items (correlated to task difficulty). The relatively new approach used in this study has the advantage of providing: (a) statistical significance of the hemispheric specialized regions for a given language task and (b) supplementary information in terms of paradigm condition-specificity of the activated regions. The results (standard hemispheric specialized regions for a semantic and for a phonological task) obtained in healthy subjects may constitute a basement for mapping language and assessing hemispheric predominance in epileptic patients before surgery and avoiding post-surgical impairments of language.

  6. Functional MRI approach for assessing hemispheric predominance of regions activated by a phonological and a semantic task

    International Nuclear Information System (INIS)

    Cousin, Emilie; Peyrin, Carole; Pichat, Cedric; Lamalle, Laurent; Le Bas, Jean-Francois; Baciu, Monica

    2007-01-01

    This fMRI study performed in healthy subjects aimed at using a statistical approach in order to determine significant functional differences between hemispheres and to assess specialized regions activated during a phonological and during a semantic task. This approach ('flip' method and subsequent statistical analyses of the parameter estimates extracted from regions of interest) allows identifying: (a) hemispheric specialized regions for each language task [semantic (living categorization) and phonological (rhyme detection)] and (b) condition-specific regions with respect to paradigm conditions (task and control). Our results showed that the rhyme-specific task regions were the inferior frontal (sub-region of BA 44, 45) and left inferior parietal (BA 40, 39) lobules. Furthermore, within the inferior parietal lobule, the angular gyrus was specific to target (rhyming) items (related to successfully grapho-phonemic processing). The categorization-specific task regions were the left inferior frontal (sub-region of BA 44, 45) and superior temporal (BA 22) cortices. Furthermore, the superior temporal gyrus was related to non-target (non-living) items (correlated to task difficulty). The relatively new approach used in this study has the advantage of providing: (a) statistical significance of the hemispheric specialized regions for a given language task and (b) supplementary information in terms of paradigm condition-specificity of the activated regions. The results (standard hemispheric specialized regions for a semantic and for a phonological task) obtained in healthy subjects may constitute a basement for mapping language and assessing hemispheric predominance in epileptic patients before surgery and avoiding post-surgical impairments of language

  7. Structural and functional insights of β-glucosidases identified from the genome of Aspergillus fumigatus

    Science.gov (United States)

    Dodda, Subba Reddy; Aich, Aparajita; Sarkar, Nibedita; Jain, Piyush; Jain, Sneha; Mondal, Sudipa; Aikat, Kaustav; Mukhopadhyay, Sudit S.

    2018-03-01

    Thermostable glucose tolerant β-glucosidase from Aspergillus species has attracted worldwide interest for their potentiality in industrial applications and bioethanol production. A strain of Aspergillus fumigatus (AfNITDGPKA3) identified by our laboratory from straw retting ground showed higher cellulase activity, specifically the β-glucosidase activity, compared to other contemporary strains. Though A. fumigatus has been known for high cellulase activity, detailed identification and characterization of the cellulase genes from their genome is yet to be done. In this work we have been analyzed the cellulase genes from the genome sequence database of Aspergillus fumigatus (Af293). Genome analysis suggests two cellobiohydrolase, eleven endoglucanase and seventeen β-glucosidase genes present. β-Glucosidase genes belong to either Glycohydro1 (GH1 or Bgl1) or Glycohydro3 (GH3 or Bgl3) family. The sequence similarity suggests that Bgl1 and Bgl3 of A. fumagatus are phylogenetically close to those of A. fisheri and A. oryzae. The modelled structure of the Bgl1 predicts the (β/α)8 barrel type structure with deep and narrow active site, whereas, Bgl3 shows the (α/β)8 barrel and (α/β)6 sandwich structure with shallow and open active site. Docking results suggest that amino acids Glu544, Glu466, Trp408,Trp567,Tyr44,Tyr222,Tyr770,Asp844,Asp537,Asn212,Asn217 of Bgl3 and Asp224,Asn242,Glu440, Glu445, Tyr367, Tyr365,Thr994,Trp435,Trp446 of Bgl1 are involved in the hydrolysis. Binding affinity analyses suggest that Bgl3 and Bgl1 enzymes are more active on the substrates like 4-methylumbelliferyl glycoside (MUG) and p-nitrophenyl-β-D-1, 4-glucopyranoside (pNPG) than on cellobiose. Further docking with glucose suggests that Bgl1 is more glucose tolerant than Bgl3. Analysis of the Aspergillus fumigatus genome may help to identify a β-glucosidase enzyme with better property and the structural information may help to develop an engineered recombinant enzyme.

  8. Regional Lung Function Profiles of Stage I and III Lung Cancer Patients: An Evaluation for Functional Avoidance Radiation Therapy

    International Nuclear Information System (INIS)

    Vinogradskiy, Yevgeniy; Schubert, Leah; Diot, Quentin; Waxweiller, Timothy; Koo, Phillip; Castillo, Richard; Castillo, Edward; Guerrero, Thomas; Rusthoven, Chad; Gaspar, Laurie; Kavanagh, Brian; Miften, Moyed

    2016-01-01

    Purpose: The development of clinical trials is underway to use 4-dimensional computed tomography (4DCT) ventilation imaging to preferentially spare functional lung in patients undergoing radiation therapy. The purpose of this work was to generate data to aide with clinical trial design by retrospectively characterizing dosimetric and functional profiles for patients with different stages of lung cancer. Methods and Materials: A total of 118 lung cancer patients (36% stage I and 64% stage III) from 2 institutions were used for the study. A 4DCT-ventilation map was calculated using the patient's 4DCT imaging, deformable image registration, and a density-change–based algorithm. To assess each patient's spatial ventilation profile both quantitative and qualitative metrics were developed, including an observer-based defect observation and metrics based on the ventilation in each lung third. For each patient we used the clinical doses to calculate functionally weighted mean lung doses and metrics that assessed the interplay between the spatial location of the dose and high-functioning lung. Results: Both qualitative and quantitative metrics revealed a significant difference in functional profiles between the 2 stage groups (P<.01). We determined that 65% of stage III and 28% of stage I patients had ventilation defects. Average functionally weighted mean lung dose was 19.6 Gy and 5.4 Gy for stage III and I patients, respectively, with both groups containing patients with large spatial overlap between dose and high-function regions. Conclusion: Our 118-patient retrospective study found that 65% of stage III patients have regionally variant ventilation profiles that are suitable for functional avoidance. Our results suggest that regardless of disease stage, it is possible to have unique spatial interplay between dose and high-functional lung, highlighting the importance of evaluating the function of each patient and developing a personalized functional avoidance

  9. Regional Lung Function Profiles of Stage I and III Lung Cancer Patients: An Evaluation for Functional Avoidance Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Vinogradskiy, Yevgeniy, E-mail: yevgeniy.vinogradskiy@ucdenver.edu [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Schubert, Leah; Diot, Quentin; Waxweiller, Timothy [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Koo, Phillip [Department of Radiology, University of Colorado School of Medicine, Aurora, Colorado (United States); Castillo, Richard [Department of Radiation Oncology, University of Texas Medical Branch, Galveston, Texas (United States); Castillo, Edward; Guerrero, Thomas [Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan (United States); Rusthoven, Chad; Gaspar, Laurie; Kavanagh, Brian; Miften, Moyed [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States)

    2016-07-15

    Purpose: The development of clinical trials is underway to use 4-dimensional computed tomography (4DCT) ventilation imaging to preferentially spare functional lung in patients undergoing radiation therapy. The purpose of this work was to generate data to aide with clinical trial design by retrospectively characterizing dosimetric and functional profiles for patients with different stages of lung cancer. Methods and Materials: A total of 118 lung cancer patients (36% stage I and 64% stage III) from 2 institutions were used for the study. A 4DCT-ventilation map was calculated using the patient's 4DCT imaging, deformable image registration, and a density-change–based algorithm. To assess each patient's spatial ventilation profile both quantitative and qualitative metrics were developed, including an observer-based defect observation and metrics based on the ventilation in each lung third. For each patient we used the clinical doses to calculate functionally weighted mean lung doses and metrics that assessed the interplay between the spatial location of the dose and high-functioning lung. Results: Both qualitative and quantitative metrics revealed a significant difference in functional profiles between the 2 stage groups (P<.01). We determined that 65% of stage III and 28% of stage I patients had ventilation defects. Average functionally weighted mean lung dose was 19.6 Gy and 5.4 Gy for stage III and I patients, respectively, with both groups containing patients with large spatial overlap between dose and high-function regions. Conclusion: Our 118-patient retrospective study found that 65% of stage III patients have regionally variant ventilation profiles that are suitable for functional avoidance. Our results suggest that regardless of disease stage, it is possible to have unique spatial interplay between dose and high-functional lung, highlighting the importance of evaluating the function of each patient and developing a personalized functional

  10. Using Functional or Structural Magnetic Resonance Images and Personal Characteristic Data to Identify ADHD and Autism.

    Directory of Open Access Journals (Sweden)

    Sina Ghiassian

    Full Text Available A clinical tool that can diagnose psychiatric illness using functional or structural magnetic resonance (MR brain images has the potential to greatly assist physicians and improve treatment efficacy. Working toward the goal of automated diagnosis, we propose an approach for automated classification of ADHD and autism based on histogram of oriented gradients (HOG features extracted from MR brain images, as well as personal characteristic data features. We describe a learning algorithm that can produce effective classifiers for ADHD and autism when run on two large public datasets. The algorithm is able to distinguish ADHD from control with hold-out accuracy of 69.6% (over baseline 55.0% using personal characteristics and structural brain scan features when trained on the ADHD-200 dataset (769 participants in training set, 171 in test set. It is able to distinguish autism from control with hold-out accuracy of 65.0% (over baseline 51.6% using functional images with personal characteristic data when trained on the Autism Brain Imaging Data Exchange (ABIDE dataset (889 participants in training set, 222 in test set. These results outperform all previously presented methods on both datasets. To our knowledge, this is the first demonstration of a single automated learning process that can produce classifiers for distinguishing patients vs. controls from brain imaging data with above-chance accuracy on large datasets for two different psychiatric illnesses (ADHD and autism. Working toward clinical applications requires robustness against real-world conditions, including the substantial variability that often exists among data collected at different institutions. It is therefore important that our algorithm was successful with the large ADHD-200 and ABIDE datasets, which include data from hundreds of participants collected at multiple institutions. While the resulting classifiers are not yet clinically relevant, this work shows that there is a signal in

  11. Covariance Association Test (CVAT) Identifies Genetic Markers Associated with Schizophrenia in Functionally Associated Biological Processes.

    Science.gov (United States)

    Rohde, Palle Duun; Demontis, Ditte; Cuyabano, Beatriz Castro Dias; Børglum, Anders D; Sørensen, Peter

    2016-08-01

    Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited power to detect genetic markers with small effects. Instead, aggregating genetic markers based on biological information might increase the power to identify sets of genetic markers of etiological significance. Several set test methods have been proposed: Here we propose a new set test derived from genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT was among the top performers. When extending CVAT to utilize a mixture of SNP effects, we found an increase in power to detect the causal sets. Applying the methods to a Danish schizophrenia case-control data set, we found genomic evidence for association of schizophrenia with vitamin A metabolism and immunological responses, which previously have been implicated with schizophrenia based on experimental and observational studies. Copyright © 2016 by the Genetics Society of America.

  12. Strain-encoding cardiovascular magnetic resonance for assessment of right-ventricular regional function

    Directory of Open Access Journals (Sweden)

    Abraham M Roselle

    2008-07-01

    Full Text Available Abstract Background Tissue tagging by cardiovascular magnetic resonance (CMR is a comprehensive method for the assessment of cardiac regional function. However, imaging the right ventricle (RV using this technique is problematic due to the thin wall of the RV relative to tag spacing which limits assessment of regional function using conventional in-plane tagging. Hypothesis We hypothesize that the use of through-plane tags in the strain-encoding (SENC CMR technique would result in reproducible measurements of the RV regional function due to the high image quality and spatial resolution possible with SENC. Aim To test the intra- and inter-observer variabilities of RV peak systolic strain measurements with SENC CMR for assessment of RV regional function (systolic strain in healthy volunteers. Methods Healthy volunteers (n = 21 were imaged using SENC. A four-chamber view was acquired in a single breath-hold. Circumferential strain was measured during systole at six equidistant points along the RV free wall. Peak contraction is defined as the maximum value of circumferential strain averaged from the six points, and regional function is defined as the strain value at each point at the time of peak contraction. Results Mean values for peak circumferential strain (± standard deviation of the basal, mid, and apical regions of the RV free wall were -20.4 ± 2.9%, -18.8 ± 3.9%, and -16.5 ± 5.7%, Altman plots showed good intra- and inter-observer agreements with mean difference of 0.11% and 0.32% and limits of agreement of -4.038 to 4.174 and -4.903 to 5.836, respectively. Conclusion SENC CMR allows for rapid quantification of RV regional function with low intra- and inter-observer variabilities, which could permit accurate quantification of regional strain in patients with RV dysfunction.

  13. Functional mechanisms of drought tolerance in subtropical maize (Zea mays L.) identified using genome-wide association mapping.

    Science.gov (United States)

    Thirunavukkarasu, Nepolean; Hossain, Firoz; Arora, Kanika; Sharma, Rinku; Shiriga, Kaliyugam; Mittal, Swati; Mohan, Sweta; Namratha, Pottekatt Mohanlal; Dogga, Sreelatha; Rani, Tikka Shobha; Katragadda, Sumalini; Rathore, Abhishek; Shah, Trushar; Mohapatra, Trilochan; Gupta, Hari Shankar

    2014-12-24

    Earlier studies were focused on the genetics of temperate and tropical maize under drought. We identified genetic loci and their association with functional mechanisms in 240 accessions of subtropical maize using a high-density marker set under water stress. Out of 61 significant SNPs (11 were false-discovery-rate-corrected associations), identified across agronomic traits, models, and locations by subjecting the accessions to water stress at flowering stage, 48% were associated with drought-tolerant genes. Maize gene models revealed that SNPs mapped for agronomic traits were in fact associated with number of functional traits as follows: stomatal closure, 28; flowering, 15; root development, 5; detoxification, 4; and reduced water potential, 2. Interactions of these SNPS through the functional traits could lead to drought tolerance. The SNPs associated with ABA-dependent signalling pathways played a major role in the plant's response to stress by regulating a series of functions including flowering, root development, auxin metabolism, guard cell functions, and scavenging reactive oxygen species (ROS). ABA signalling genes regulate flowering through epigenetic changes in stress-responsive genes. ROS generated by ABA signalling are reduced by the interplay between ethylene, ABA, and detoxification signalling transductions. Integration of ABA-signalling genes with auxin-inducible genes regulates root development which in turn, maintains the water balance by regulating electrochemical gradient in plant. Several genes are directly or indirectly involved in the functioning of agronomic traits related to water stress. Genes involved in these crucial biological functions interacted significantly in order to maintain the primary as well as exclusive functions related to coping with water stress. SNPs associated with drought-tolerant genes involved in strategic biological functions will be useful to understand the mechanisms of drought tolerance in subtropical maize.

  14. Meta-genome-wide association studies identify a locus on chromosome 1 and multiple variants in the MHC region for serum C-peptide in type 1 diabetes.

    Science.gov (United States)

    Roshandel, Delnaz; Gubitosi-Klug, Rose; Bull, Shelley B; Canty, Angelo J; Pezzolesi, Marcus G; King, George L; Keenan, Hillary A; Snell-Bergeon, Janet K; Maahs, David M; Klein, Ronald; Klein, Barbara E K; Orchard, Trevor J; Costacou, Tina; Weedon, Michael N; Oram, Richard A; Paterson, Andrew D

    2018-05-01

    The aim of this study was to identify genetic variants associated with beta cell function in type 1 diabetes, as measured by serum C-peptide levels, through meta-genome-wide association studies (meta-GWAS). We performed a meta-GWAS to combine the results from five studies in type 1 diabetes with cross-sectionally measured stimulated, fasting or random C-peptide levels, including 3479 European participants. The p values across studies were combined, taking into account sample size and direction of effect. We also performed separate meta-GWAS for stimulated (n = 1303), fasting (n = 2019) and random (n = 1497) C-peptide levels. In the meta-GWAS for stimulated/fasting/random C-peptide levels, a SNP on chromosome 1, rs559047 (Chr1:238753916, T>A, minor allele frequency [MAF] 0.24-0.26), was associated with C-peptide (p = 4.13 × 10 -8 ), meeting the genome-wide significance threshold (p C>T, MAF 0.07-0.10, p = 8.43 × 10 -8 ). In the stimulated C-peptide meta-GWAS, rs61211515 (Chr6:30100975, T/-, MAF 0.17-0.19) in the MHC region was associated with stimulated C-peptide (β [SE] = - 0.39 [0.07], p = 9.72 × 10 -8 ). rs61211515 was also associated with the rate of stimulated C-peptide decline over time in a subset of individuals (n = 258) with annual repeated measures for up to 6 years (p = 0.02). In the meta-GWAS of random C-peptide, another MHC region, SNP rs3135002 (Chr6:32668439, C>A, MAF 0.02-0.06), was associated with C-peptide (p = 3.49 × 10 -8 ). Conditional analyses suggested that the three identified variants in the MHC region were independent of each other. rs9260151 and rs3135002 have been associated with type 1 diabetes, whereas rs559047 and rs61211515 have not been associated with a risk of developing type 1 diabetes. We identified a locus on chromosome 1 and multiple variants in the MHC region, at least some of which were distinct from type 1 diabetes risk loci, that were associated with C

  15. Identifying selected regions from heterozygosity and divergence using a light-coverage genomic dataset from two human populations.

    Directory of Open Access Journals (Sweden)

    Taras K Oleksyk

    2008-03-01

    Full Text Available When a selective sweep occurs in the chromosomal region around a target gene in two populations that have recently separated, it produces three dramatic genomic consequences: 1 decreased multi-locus heterozygosity in the region; 2 elevated or diminished genetic divergence (F(ST of multiple polymorphic variants adjacent to the selected locus between the divergent populations, due to the alternative fixation of alleles; and 3 a consequent regional increase in the variance of F(ST (S(2F(ST for the same clustered variants, due to the increased alternative fixation of alleles in the loci surrounding the selection target. In the first part of our study, to search for potential targets of directional selection, we developed and validated a resampling-based computational approach; we then scanned an array of 31 different-sized moving windows of SNP variants (5-65 SNPs across the human genome in a set of European and African American population samples with 183,997 SNP loci after correcting for the recombination rate variation. The analysis revealed 180 regions of recent selection with very strong evidence in either population or both. In the second part of our study, we compared the newly discovered putative regions to those sites previously postulated in the literature, using methods based on inspecting patterns of linkage disequilibrium, population divergence and other methodologies. The newly found regions were cross-validated with those found in nine other studies that have searched for selection signals. Our study was replicated especially well in those regions confirmed by three or more studies. These validated regions were independently verified, using a combination of different methods and different databases in other studies, and should include fewer false positives. The main strength of our analysis method compared to others is that it does not require dense genotyping and therefore can be used with data from population-based genome SNP scans

  16. Cross-cultural consistency and diversity in intrinsic functional organization of Broca's Region.

    Science.gov (United States)

    Zhang, Yu; Fan, Lingzhong; Caspers, Svenja; Heim, Stefan; Song, Ming; Liu, Cirong; Mo, Yin; Eickhoff, Simon B; Amunts, Katrin; Jiang, Tianzi

    2017-04-15

    As a core language area, Broca's region was consistently activated in a variety of language studies even across different language systems. Moreover, a high degree of structural and functional heterogeneity in Broca's region has been reported in many studies. This raised the issue of how the intrinsic organization of Broca's region effects by different language experiences in light of its subdivisions. To address this question, we used multi-center resting-state fMRI data to explore the cross-cultural consistency and diversity of Broca's region in terms of its subdivisions, connectivity patterns and modularity organization in Chinese and German speakers. A consistent topological organization of the 13 subdivisions within the extended Broca's region was revealed on the basis of a new in-vivo parcellation map, which corresponded well to the previously reported receptorarchitectonic map. Based on this parcellation map, consistent functional connectivity patterns and modularity organization of these subdivisions were found. Some cultural difference in the functional connectivity patterns was also found, for instance stronger connectivity in Chinese subjects between area 6v2 and the motor hand area, as well as higher correlations between area 45p and middle frontal gyrus. Our study suggests that a generally invariant organization of Broca's region, together with certain regulations of different language experiences on functional connectivity, might exists to support language processing in human brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. A functional interaction approach to the definition of meso regions: The case of the Czech Republic

    Directory of Open Access Journals (Sweden)

    Erlebach Martin

    2016-06-01

    Full Text Available The definition of functional meso regions for the territory of the Czech Republic is articulated in this article. Functional regions reflect horizontal interactions in space and are presented as a useful tool for various types of geographical analyses, and also for spatial planning, economic policy designs, etc. This paper attempts to add to the discussion on the need to delineate areal units at different hierarchical levels, and to understand the functional flows and spatial behaviours of the population in a given space. Three agglomerative methods are applied in the paper (the CURDS regionalisation algorithm, Intramax, and cluster analysis, and they have not been used previously in Czech geography for the delineation of functional meso regions. Existing functional regions at the micro-level, based on daily travel-to-work flows from the 2001 census, have served as the building blocks. The analyses have produced five regional systems at the meso level, based on daily labour commuting movements of the population. Basic statistics and a characterisation of these systems are provided in this paper.

  18. In Silico Functional Networks Identified in Fish Nucleated Red Blood Cells by Means of Transcriptomic and Proteomic Profiling.

    Science.gov (United States)

    Puente-Marin, Sara; Nombela, Iván; Ciordia, Sergio; Mena, María Carmen; Chico, Verónica; Coll, Julio; Ortega-Villaizan, María Del Mar

    2018-04-09

    Nucleated red blood cells (RBCs) of fish have, in the last decade, been implicated in several immune-related functions, such as antiviral response, phagocytosis or cytokine-mediated signaling. RNA-sequencing (RNA-seq) and label-free shotgun proteomic analyses were carried out for in silico functional pathway profiling of rainbow trout RBCs. For RNA-seq, a de novo assembly was conducted, in order to create a transcriptome database for RBCs. For proteome profiling, we developed a proteomic method that combined: (a) fractionation into cytosolic and membrane fractions, (b) hemoglobin removal of the cytosolic fraction, (c) protein digestion, and (d) a novel step with pH reversed-phase peptide fractionation and final Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometric (LC ESI-MS/MS) analysis of each fraction. Combined transcriptome- and proteome- sequencing data identified, in silico, novel and striking immune functional networks for rainbow trout nucleated RBCs, which are mainly linked to innate and adaptive immunity. Functional pathways related to regulation of hematopoietic cell differentiation, antigen presentation via major histocompatibility complex class II (MHCII), leukocyte differentiation and regulation of leukocyte activation were identified. These preliminary findings further implicate nucleated RBCs in immune function, such as antigen presentation and leukocyte activation.

  19. In Silico Functional Networks Identified in Fish Nucleated Red Blood Cells by Means of Transcriptomic and Proteomic Profiling

    Directory of Open Access Journals (Sweden)

    Sara Puente-Marin

    2018-04-01

    Full Text Available Nucleated red blood cells (RBCs of fish have, in the last decade, been implicated in several immune-related functions, such as antiviral response, phagocytosis or cytokine-mediated signaling. RNA-sequencing (RNA-seq and label-free shotgun proteomic analyses were carried out for in silico functional pathway profiling of rainbow trout RBCs. For RNA-seq, a de novo assembly was conducted, in order to create a transcriptome database for RBCs. For proteome profiling, we developed a proteomic method that combined: (a fractionation into cytosolic and membrane fractions, (b hemoglobin removal of the cytosolic fraction, (c protein digestion, and (d a novel step with pH reversed-phase peptide fractionation and final Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometric (LC ESI-MS/MS analysis of each fraction. Combined transcriptome- and proteome- sequencing data identified, in silico, novel and striking immune functional networks for rainbow trout nucleated RBCs, which are mainly linked to innate and adaptive immunity. Functional pathways related to regulation of hematopoietic cell differentiation, antigen presentation via major histocompatibility complex class II (MHCII, leukocyte differentiation and regulation of leukocyte activation were identified. These preliminary findings further implicate nucleated RBCs in immune function, such as antigen presentation and leukocyte activation.

  20. SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function

    OpenAIRE

    Li, Man; Li, Yong; Weeks, Olivia; Mijatovic, Vladan; Teumer, Alexander; Huffman, Jennifer E; Tromp, Gerard; Fuchsberger, Christian; Gorski, Mathias; Lyytikäinen, Leo-Pekka; Nutile, Teresa; Sedaghat, Sanaz; Sorice, Rossella; Tin, Adrienne; Yang, Qiong

    2017-01-01

    Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (nStage1: 111,666; nStage2: 48,343). In single-variant analyses, we identified single nucleotide polymorphi...

  1. Gross–Tulub polaron functional in the region of intermediate and strong coupling

    Directory of Open Access Journals (Sweden)

    N.I. Kashirina

    2017-10-01

    Full Text Available Properties of the polaron functional obtained as a result of averaging the Fröhlich Hamiltonian on the translation-invariant function have been investigated. The polaron functional can be represented in two different forms. It has been shown that the functional of translationally invariant Gross–Tulub polaron cannot be applied in the strong coupling region, where the real part of the complex quantity takes negative values. The function coincides in its structure with the dynamic susceptibility of degenerate electron gas. The necessary condition for obtaining correct results is investigation of the region of admissible values of the Gross–Tulub functional depending on properties of the function , variational parameters, and the electron-phonon interaction parameter α (Fröhlich coupling constant. A simple and exact formula for the recoil energy of the translationally invariant polaron has been derived, which makes it possible to extend the range of admissible values of the parameters of the electron-phonon interaction to the region of extremely strong coupling (α > 10, where . Numerical investigation of different forms of polaron functionals obtained using the field theory methods has been carried out.

  2. Resistance exercise induces region-specific adaptations in anterior pituitary gland structure and function in rats.

    Science.gov (United States)

    Kraemer, William J; Flanagan, Shawn D; Volek, Jeff S; Nindl, Bradley C; Vingren, Jakob L; Dunn-Lewis, Courtenay; Comstock, Brett A; Hooper, David R; Szivak, Tunde K; Looney, David P; Maresh, Carl M; Hymer, Wesley C

    2013-12-01

    The anterior pituitary gland (AP) increases growth hormone (GH) secretion in response to resistance exercise (RE), but the nature of AP adaptations to RE is unknown. To that end, we examined the effects of RE on regional AP somatotroph GH release, structure, and relative quantity. Thirty-six Sprague-Dawley rats were assigned to one of four groups: 1) no training or acute exercise (NT-NEX); 2) no training with acute exercise (NT-EX); 3) resistance training without acute exercise (RT-NEX); 4) resistance training with acute exercise (RT-EX). RE incorporated 10, 1 m-weighted ladder climbs at an 85° angle. RT groups trained 3 days/wk for 7 wk, progressively. After death, trunk blood was collected, and each AP was divided into quadrants (ventral-dorsal and left-right). We measured: 1) trunk plasma GH; 2) somatotroph GH release; 3) somatotroph size; 4) somatotroph secretory content; and 5) percent of AP cells identified as somatotrophs. Trunk GH differed by group (NT-NEX, 8.9 ± 2.4 μg/l; RT-NEX, 9.2 ± 3.5 μg/l; NT-EX, 15.6 ± 3.4 μg/l; RT-EX, 23.4 ± 4.6 μg/l). RT-EX demonstrated greater somatotroph GH release than all other groups, predominantly in ventral regions (P pituitary gland. RE training appears to induce dynamic adaptations in somatotroph structure and function.

  3. Identification of functional DNA variants in the constitutive promoter region of MDM2

    Directory of Open Access Journals (Sweden)

    Lalonde Marie-Eve

    2012-09-01

    Full Text Available Abstract Although mutations in the oncoprotein murine double minute 2 (MDM2 are rare, MDM2 gene overexpression has been observed in several human tumors. Given that even modest changes in MDM2 levels might influence the p53 tumor suppressor signaling pathway, we postulated that sequence variation in the promoter region of MDM2 could lead to disregulated expression and variation in gene dosage. Two promoters have been reported for MDM2; an internal promoter (P2, which is located near the end of intron 1 and is p53-responsive, and an upstream constitutive promoter (P1, which is p53-independent. Both promoter regions contain DNA variants that could influence the expression levels of MDM2, including the well-studied single nucleotide polymorphism (SNP SNP309, which is located in the promoter P2; i.e., upstream of exon 2. In this report, we screened the promoter P1 for DNA variants and assessed the functional impact of the corresponding SNPs. Using the dbSNP database and genotyping validation in individuals of European descent, we identified three common SNPs (−1494 G > A; indel 40 bp; and −182 C > G. Three major promoter haplotypes were inferred by using these three promoter SNPs together with rs2279744 (SNP309. Following subcloning into a gene reporter system, we found that two of the haplotypes significantly influenced MDM2 promoter activity in a haplotype-specific manner. Site-directed mutagenesis experiments indicated that the 40 bp insertion/deletion variation is causing the observed allelic promoter activity. This study suggests that part of the variability in the MDM2 expression levels could be explained by allelic p53-independent P1 promoter activity.

  4. Functional connections between activated and deactivated brain regions mediate emotional interference during externally directed cognition.

    Science.gov (United States)

    Di Plinio, Simone; Ferri, Francesca; Marzetti, Laura; Romani, Gian Luca; Northoff, Georg; Pizzella, Vittorio

    2018-04-24

    Recent evidence shows that task-deactivations are functionally relevant for cognitive performance. Indeed, higher cognitive engagement has been associated with higher suppression of activity in task-deactivated brain regions - usually ascribed to the Default Mode Network (DMN). Moreover, a negative correlation between these regions and areas actively engaged by the task is associated with better performance. DMN regions show positive modulation during autobiographical, social, and emotional tasks. However, it is not clear how processing of emotional stimuli affects the interplay between the DMN and executive brain regions. We studied this interplay in an fMRI experiment using emotional negative stimuli as distractors. Activity modulations induced by the emotional interference of negative stimuli were found in frontal, parietal, and visual areas, and were associated with modulations of functional connectivity between these task-activated areas and DMN regions. A worse performance was predicted both by lower activity in the superior parietal cortex and higher connectivity between visual areas and frontal DMN regions. Connectivity between right inferior frontal gyrus and several DMN regions in the left hemisphere was related to the behavioral performance. This relation was weaker in the negative than in the neutral condition, likely suggesting less functional inhibitions of DMN regions during emotional processing. These results show that both executive and DMN regions are crucial for the emotional interference process and suggest that DMN connections are related to the interplay between externally-directed and internally-focused processes. Among DMN regions, superior frontal gyrus may be a key node in regulating the interference triggered by emotional stimuli. © 2018 Wiley Periodicals, Inc.

  5. Improved diagnostic accuracy of Alzheimer's disease by combining regional cortical thickness and default mode network functional connectivity: Validated in the Alzheimer's disease neuroimaging initiative set

    International Nuclear Information System (INIS)

    Park, Ji Eun; Park, Bum Woo; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Jung; Oh, Joo Young; Shim, Woo Hyun; Lee, Jae Hong; Roh, Jee Hoon

    2017-01-01

    To identify potential imaging biomarkers of Alzheimer's disease by combining brain cortical thickness (CThk) and functional connectivity and to validate this model's diagnostic accuracy in a validation set. Data from 98 subjects was retrospectively reviewed, including a study set (n = 63) and a validation set from the Alzheimer's Disease Neuroimaging Initiative (n = 35). From each subject, data for CThk and functional connectivity of the default mode network was extracted from structural T1-weighted and resting-state functional magnetic resonance imaging. Cortical regions with significant differences between patients and healthy controls in the correlation of CThk and functional connectivity were identified in the study set. The diagnostic accuracy of functional connectivity measures combined with CThk in the identified regions was evaluated against that in the medial temporal lobes using the validation set and application of a support vector machine. Group-wise differences in the correlation of CThk and default mode network functional connectivity were identified in the superior temporal (p < 0.001) and supramarginal gyrus (p = 0.007) of the left cerebral hemisphere. Default mode network functional connectivity combined with the CThk of those two regions were more accurate than that combined with the CThk of both medial temporal lobes (91.7% vs. 75%). Combining functional information with CThk of the superior temporal and supramarginal gyri in the left cerebral hemisphere improves diagnostic accuracy, making it a potential imaging biomarker for Alzheimer's disease

  6. Identifying Regulatory Patterns at the 3'end Regions of Over-expressed and Under-expressed Genes

    KAUST Repository

    Othoum, Ghofran K

    2013-05-01

    Promoters, neighboring regulatory regions and those extending further upstream of the 5’end of genes, are considered one of the main components affecting the expression status of genes in a specific phenotype. More recently research by Chen et al. (2006, 2012) and Mapendano et al. (2010) demonstrated that the 3’end regulatory regions of genes also influence gene expression. However, the association between the regulatory regions surrounding 3’end of genes and their over- or under-expression status in a particular phenotype has not been systematically studied. The aim of this study is to ascertain if regulatory regions surrounding the 3’end of genes contain sufficient regulatory information to correlate genes with their expression status in a particular phenotype. Over- and under-expressed ovarian cancer (OC) genes were used as a model. Exploratory analysis of the 3’end regions were performed by transforming the annotated regions using principal component analysis (PCA), followed by clustering the transformed data thereby achieving a clear separation of genes with different expression status. Additionally, several classification algorithms such as Naïve Bayes, Random Forest and Support Vector Machine (SVM) were tested with different parameter settings to analyze the discriminatory capacity of the 3’end regions of genes related to their gene expression status. The best performance was achieved using the SVM classification model with 10-fold cross-validation that yielded an accuracy of 98.4%, sensitivity of 99.5% and specificity of 92.5%. For gene expression status for newly available instances, based on information derived from the 3’end regions, an SVM predictive model was developed with 10-fold cross-validation that yielded an accuracy of 67.0%, sensitivity of 73.2% and specificity of 61.0%. Moreover, building an SVM with polynomial kernel model to PCA transformed data yielded an accuracy of 83.1%, sensitivity of 92.5% and specificity of 74.8% using

  7. Identifying Regulatory Patterns at the 3'end Regions of Over-expressed and Under-expressed Genes

    KAUST Repository

    Othoum, Ghofran K

    2013-01-01

    Promoters, neighboring regulatory regions and those extending further upstream of the 5’end of genes, are considered one of the main components affecting the expression status of genes in a specific phenotype. More recently research by Chen et al. (2006, 2012) and Mapendano et al. (2010) demonstrated that the 3’end regulatory regions of genes also influence gene expression. However, the association between the regulatory regions surrounding 3’end of genes and their over- or under-expression status in a particular phenotype has not been systematically studied. The aim of this study is to ascertain if regulatory regions surrounding the 3’end of genes contain sufficient regulatory information to correlate genes with their expression status in a particular phenotype. Over- and under-expressed ovarian cancer (OC) genes were used as a model. Exploratory analysis of the 3’end regions were performed by transforming the annotated regions using principal component analysis (PCA), followed by clustering the transformed data thereby achieving a clear separation of genes with different expression status. Additionally, several classification algorithms such as Naïve Bayes, Random Forest and Support Vector Machine (SVM) were tested with different parameter settings to analyze the discriminatory capacity of the 3’end regions of genes related to their gene expression status. The best performance was achieved using the SVM classification model with 10-fold cross-validation that yielded an accuracy of 98.4%, sensitivity of 99.5% and specificity of 92.5%. For gene expression status for newly available instances, based on information derived from the 3’end regions, an SVM predictive model was developed with 10-fold cross-validation that yielded an accuracy of 67.0%, sensitivity of 73.2% and specificity of 61.0%. Moreover, building an SVM with polynomial kernel model to PCA transformed data yielded an accuracy of 83.1%, sensitivity of 92.5% and specificity of 74.8% using

  8. Overweight consumers' salient beliefs on omega-3-enriched functional foods in Australia's Illawarra region.

    Science.gov (United States)

    Patch, Craig S; Tapsell, Linda C; Williams, Peter G

    2005-01-01

    To determine consumer salient beliefs toward functional foods enriched with omega-3 fatty acids. Focus group interviews with adult consumers using the Theory of Planned Behavior (TPB) as a theoretical framework. Community-based residents living in the Illawarra region of New South Wales, Australia. Forty-two overweight participants (29 female, 13 male) aged 30 to 80 years recruited by advertisement and attending 1 of 6 focus groups, which were recorded and transcribed verbatim. Content analysis was carried out, and subcategories were developed to capture the emerging themes according to the TPB model. Most participants were aware of a range of potential benefits of omega-3 fatty acids, but they had reservations about the ability of omega-3-enriched foods to deliver a health benefit. They were concerned about whether these foods were labeled clearly and about the possibility of overdosing. Family and friends were viewed as important in introducing participants to novel foods on the market. Participants regarded dietitians as a credible source and were least trusting of food companies and scientists. Overall, participants reported that cost was a major barrier, and that they would not necessarily trade taste for health benefits. Adding omega-3 fatty acids to foods regarded as less healthful was viewed more as a gimmick rather than a real health benefit. The consumer attitudes and purchase intentions identified in this study will be helpful to educators as they plan messages and strategies to guide dietary choices related to products enriched with omega-3 fatty acids.

  9. SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function

    DEFF Research Database (Denmark)

    Li, Man; Li, Yong; Weeks, Olivia

    2017-01-01

    Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum...... creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (nStage1: 111,666; nStage2: 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (PPM1J, EDEM3, ACP1, SPEG, EYA4, CYP1A1, and ATXN2L; PStage1......associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 (P=5.4×10(-8) by sequence kernel...

  10. Integrative analysis of functional genomic annotations and sequencing data to identify rare causal variants via hierarchical modeling

    Directory of Open Access Journals (Sweden)

    Marinela eCapanu

    2015-05-01

    Full Text Available Identifying the small number of rare causal variants contributing to disease has beena major focus of investigation in recent years, but represents a formidable statisticalchallenge due to the rare frequencies with which these variants are observed. In thiscommentary we draw attention to a formal statistical framework, namely hierarchicalmodeling, to combine functional genomic annotations with sequencing data with theobjective of enhancing our ability to identify rare causal variants. Using simulations weshow that in all configurations studied, the hierarchical modeling approach has superiordiscriminatory ability compared to a recently proposed aggregate measure of deleteriousness,the Combined Annotation-Dependent Depletion (CADD score, supportingour premise that aggregate functional genomic measures can more accurately identifycausal variants when used in conjunction with sequencing data through a hierarchicalmodeling approach

  11. Nonlinear H∞ Optimal Control Scheme for an Underwater Vehicle with Regional Function Formulation

    Directory of Open Access Journals (Sweden)

    Zool H. Ismail

    2013-01-01

    Full Text Available A conventional region control technique cannot meet the demands for an accurate tracking performance in view of its inability to accommodate highly nonlinear system dynamics, imprecise hydrodynamic coefficients, and external disturbances. In this paper, a robust technique is presented for an Autonomous Underwater Vehicle (AUV with region tracking function. Within this control scheme, nonlinear H∞ and region based control schemes are used. A Lyapunov-like function is presented for stability analysis of the proposed control law. Numerical simulations are presented to demonstrate the performance of the proposed tracking control of the AUV. It is shown that the proposed control law is robust against parameter uncertainties, external disturbances, and nonlinearities and it leads to uniform ultimate boundedness of the region tracking error.

  12. Combining functional weed ecology and crop stable isotope ratios to identify cultivation intensity: a comparison of cereal production regimes in Haute Provence, France and Asturias, Spain.

    Science.gov (United States)

    Bogaard, Amy; Hodgson, John; Nitsch, Erika; Jones, Glynis; Styring, Amy; Diffey, Charlotte; Pouncett, John; Herbig, Christoph; Charles, Michael; Ertuğ, Füsun; Tugay, Osman; Filipovic, Dragana; Fraser, Rebecca

    This investigation combines two independent methods of identifying crop growing conditions and husbandry practices-functional weed ecology and crop stable carbon and nitrogen isotope analysis-in order to assess their potential for inferring the intensity of past cereal production systems using archaeobotanical assemblages. Present-day organic cereal farming in Haute Provence, France features crop varieties adapted to low-nutrient soils managed through crop rotation, with little to no manuring. Weed quadrat survey of 60 crop field transects in this region revealed that floristic variation primarily reflects geographical differences. Functional ecological weed data clearly distinguish the Provence fields from those surveyed in a previous study of intensively managed spelt wheat in Asturias, north-western Spain: as expected, weed ecological data reflect higher soil fertility and disturbance in Asturias. Similarly, crop stable nitrogen isotope values distinguish between intensive manuring in Asturias and long-term cultivation with minimal manuring in Haute Provence. The new model of cereal cultivation intensity based on weed ecology and crop isotope values in Haute Provence and Asturias was tested through application to two other present-day regimes, successfully identifying a high-intensity regime in the Sighisoara region, Romania, and low-intensity production in Kastamonu, Turkey. Application of this new model to Neolithic archaeobotanical assemblages in central Europe suggests that early farming tended to be intensive, and likely incorporated manuring, but also exhibited considerable variation, providing a finer grained understanding of cultivation intensity than previously available.

  13. Deep UV Luminosity Functions at the Infall Region of the Coma Cluster

    Science.gov (United States)

    Hammer, D. M.; Hornschemeier, A. E.; Salim, S.; Smith, R.; Jenkins, L.; Mobasher, B.; Miller, N.; Ferguson, H.

    2011-01-01

    We have used deep GALEX observations at the infall region of the Coma cluster to measure the faintest UV luminosity functions (LFs) presented for a rich galaxy cluster thus far. The Coma UV LFs are measured to M(sub uv) = -10.5 in the GALEX FUV and NUV bands, or 3.5 mag fainter than previous studies, and reach the dwarf early-type galaxy population in Coma for the first time. The Schechter faint-end slopes (alpha approximately equal to -1.39 in both GALEX bands) are shallower than reported in previous Coma UV LF studies owing to a flatter LF at faint magnitudes. A Gaussian-plus-Schechter model provides a slightly better parametrization of the UV LFs resulting in a faint-end slope of alpha approximately equal to -1.15 in both GALEX bands. The two-component model gives faint-end slopes shallower than alpha = -1 (a turnover) for the LFs constructed separately for passive and star forming galaxies. The UV LFs for star forming galaxies show a turnover at M(sub UV) approximately equal to -14 owing to a deficit of dwarf star forming galaxies in Coma with stellar masses below M(sub *) = 10(sup 8) solar mass. A similar turnover is identified in recent UV LFs measured for the Virgo cluster suggesting this may be a common feature of local galaxy clusters, whereas the field UV LFs continue to rise at faint magnitudes. We did not identify an excess of passive galaxies as would be expected if the missing dwarf star forming galaxies were quenched inside the cluster. In fact, the LFs for both dwarf passive and star forming galaxies show the same turnover at faint magnitudes. We discuss the possible origin of the missing dwarf star forming galaxies in Coma and their expected properties based on comparisons to local field galaxies.

  14. DEEP ULTRAVIOLET LUMINOSITY FUNCTIONS AT THE INFALL REGION OF THE COMA CLUSTER

    International Nuclear Information System (INIS)

    Hammer, D. M.; Hornschemeier, A. E.; Jenkins, L.; Salim, S.; Smith, R.; Mobasher, B.; Miller, N.; Ferguson, H.

    2012-01-01

    We have used deep GALEX observations at the infall region of the Coma cluster to measure the faintest ultraviolet (UV) luminosity functions (LFs) presented for a rich galaxy cluster thus far. The Coma UV LFs are measured to M UV = –10.5 in the GALEX FUV and NUV bands, or 3.5 mag fainter than previous studies, and reach the dwarf early-type galaxy population in Coma for the first time. The Schechter faint-end slopes (α ≈ –1.39 in both GALEX bands) are shallower than reported in previous Coma UV LF studies owing to a flatter LF at faint magnitudes. A Gaussian-plus-Schechter model provides a slightly better parameterization of the UV LFs resulting in a faint-end slope of α ≈ –1.15 in both GALEX bands. The two-component model gives faint-end slopes shallower than α = –1 (a turnover) for the LFs constructed separately for passive and star-forming galaxies. The UV LFs for star-forming galaxies show a turnover at M UV ≈ –14 owing to a deficit of dwarf star-forming galaxies in Coma with stellar masses below M * = 10 8 M ☉ . A similar turnover is identified in recent UV LFs measured for the Virgo cluster suggesting this may be a common feature of local galaxy clusters, whereas the field UV LFs continue to rise at faint magnitudes. We did not identify an excess of passive galaxies as would be expected if the missing dwarf star-forming galaxies were quenched inside the cluster. In fact, the LFs for both dwarf passive and star-forming galaxies show the same turnover at faint magnitudes. We discuss the possible origin of the missing dwarf star-forming galaxies in Coma and their expected properties based on comparisons to local field galaxies.

  15. Genome Regions Associated with Functional Performance of Soybean Stem Fibers in Polypropylene Thermoplastic Composites.

    Directory of Open Access Journals (Sweden)

    Yarmilla Reinprecht

    Full Text Available Plant fibers can be used to produce composite materials for automobile parts, thus reducing plastic used in their manufacture, overall vehicle weight and fuel consumption when they replace mineral fillers and glass fibers. Soybean stem residues are, potentially, significant sources of inexpensive, renewable and biodegradable natural fibers, but are not curretly used for biocomposite production due to the functional properties of their fibers in composites being unknown. The current study was initiated to investigate the effects of plant genotype on the performance characteristics of soybean stem fibers when incorporated into a polypropylene (PP matrix using a selective phenotyping approach. Fibers from 50 lines of a recombinant inbred line population (169 RILs grown in different environments were incorporated into PP at 20% (wt/wt by extrusion. Test samples were injection molded and characterized for their mechanical properties. The performance of stem fibers in the composites was significantly affected by genotype and environment. Fibers from different genotypes had significantly different chemical compositions, thus composites prepared with these fibers displayed different physical properties. This study demonstrates that thermoplastic composites with soybean stem-derived fibers have mechanical properties that are equivalent or better than wheat straw fiber composites currently being used for manufacturing interior automotive parts. The addition of soybean stem residues improved flexural, tensile and impact properties of the composites. Furthermore, by linkage and in silico mapping we identified genomic regions to which quantitative trait loci (QTL for compositional and functional properties of soybean stem fibers in thermoplastic composites, as well as genes for cell wall synthesis, were co-localized. These results may lead to the development of high value uses for soybean stem residue.

  16. Molecular and Functional Properties of Regional Astrocytes in the Adult Brain.

    Science.gov (United States)

    Morel, Lydie; Chiang, Ming Sum R; Higashimori, Haruki; Shoneye, Temitope; Iyer, Lakshmanan K; Yelick, Julia; Tai, Albert; Yang, Yongjie

    2017-09-06

    The molecular signature and functional properties of astroglial subtypes in the adult CNS remain largely undefined. By using translational ribosome affinity purification followed by RNA-Seq, we profiled astroglial ribosome-associated (presumably translating) mRNAs in major cortical and subcortical brain regions (cortex, hippocampus, caudate-putamen, nucleus accumbens, thalamus, and hypothalamus) of BAC aldh1l1 -translational ribosome affinity purification (TRAP) mice (both sexes). We found that the expression of astroglial translating mRNAs closely follows the dorsoventral axis, especially from cortex/hippocampus to thalamus/hypothalamus posteriorly. This region-specific expression pattern of genes, such as synaptogenic modulator sparc and transcriptional factors ( emx2 , lhx2 , and hopx ), was validated by qRT-PCR and immunostaining in brain sections. Interestingly, cortical or subcortical astrocytes selectively promote neurite growth and synaptic activity of neurons only from the same region in mismatched cocultures, exhibiting region-matched astrocyte to neuron communication. Overall, these results generated new molecular signature of astrocyte types in the adult CNS, providing insights into their origin and functional diversity. SIGNIFICANCE STATEMENT We investigated the in vivo molecular and functional heterogeneity of astrocytes inter-regionally from adult brain. Our results showed that the expression pattern of ribosome-associated mRNA profiles in astrocytes closely follows the dorsoventral axis, especially posteriorly from cortex/hippocampus to thalamus/hypothalamus. In line with this, our functional results further demonstrated region-selective roles of cortical and subcortical astrocytes in regulating cortical or subcortical neuronal synaptogenesis and maturation. These in vivo studies provide a previously uncharacterized and important molecular atlas for exploring region-specific astroglial functions. Copyright © 2017 the authors 0270-6474/17/378706-12$15.00/0.

  17. Evaluation of the optimum region for mammographic system using computer simulation to study modulation transfer functions

    International Nuclear Information System (INIS)

    Oliveira, Isaura N. Sombra; Schiable, Homero; Porcel, Naider T.; Frere, Annie F.; Marques, Paulo M.A.

    1996-01-01

    An investigation of the 'optimum region' of the radiation field considering mammographic systems is studied. Such a region was defined in previous works as the field range where the system has its best performance and sharpest images. This study is based on a correlation of two methods for evaluating radiologic imaging systems, both using computer simulation in order to determine modulation transfer functions (MTFs) due to the X-ray tube focal spot in several field orientation and locations

  18. Identification of putative regulatory motifs in the upstream regions of co-expressed functional groups of genes in Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Joshi NV

    2009-01-01

    Full Text Available Abstract Background Regulation of gene expression in Plasmodium falciparum (Pf remains poorly understood. While over half the genes are estimated to be regulated at the transcriptional level, few regulatory motifs and transcription regulators have been found. Results The study seeks to identify putative regulatory motifs in the upstream regions of 13 functional groups of genes expressed in the intraerythrocytic developmental cycle of Pf. Three motif-discovery programs were used for the purpose, and motifs were searched for only on the gene coding strand. Four motifs – the 'G-rich', the 'C-rich', the 'TGTG' and the 'CACA' motifs – were identified, and zero to all four of these occur in the 13 sets of upstream regions. The 'CACA motif' was absent in functional groups expressed during the ring to early trophozoite transition. For functional groups expressed in each transition, the motifs tended to be similar. Upstream motifs in some functional groups showed 'positional conservation' by occurring at similar positions relative to the translational start site (TLS; this increases their significance as regulatory motifs. In the ribonucleotide synthesis, mitochondrial, proteasome and organellar translation machinery genes, G-rich, C-rich, CACA and TGTG motifs, respectively, occur with striking positional conservation. In the organellar translation machinery group, G-rich motifs occur close to the TLS. The same motifs were sometimes identified for multiple functional groups; differences in location and abundance of the motifs appear to ensure different modes of action. Conclusion The identification of positionally conserved over-represented upstream motifs throws light on putative regulatory elements for transcription in Pf.

  19. The Responsive Amygdala: Treatment-induced Alterations in Functional Connectivity in Pediatric Complex Regional Pain Syndrome

    Science.gov (United States)

    Simons, LE; Pielech, M; Erpelding, N; Linnman, C; Moulton, E; Sava, S; Lebel, A; Serrano, P; Sethna, N; Berde, C; Becerra, L; Borsook, D

    2014-01-01

    The amygdala is a key brain region with efferent and afferent neural connections that involve complex behaviors such as pain, reward, fear and anxiety. This study evaluated resting state functional connectivity of the amygdala with cortical and subcortical regions in a group of chronic pain patients (pediatric complex regional pain syndrome) with age-gender matched controls before and after intensive physical-biobehavioral pain treatment. Our main findings include (1) enhanced functional connectivity from the amygdala to multiple cortical, subcortical, and cerebellar regions in patients compared to controls, with differences predominantly in the left amygdala in the pre-treated condition (disease state); (2) dampened hyperconnectivity from the left amygdala to the motor cortex, parietal lobe, and cingulate cortex after intensive pain rehabilitation treatment within patients with nominal differences observed among healthy controls from Time 1 to Time 2 (treatment effects); (3) functional connectivity to several regions key to fear circuitry (prefrontal cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus) correlated with higher pain-related fear scores and (4) decreases in pain-related fear associated with decreased connectivity between the amygdala and the motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest that there are rapid changes in amygdala connectivity following an aggressive treatment program in children with chronic pain and intrinsic amygdala functional connectivity activity serving as a potential indicator of treatment response. PMID:24861582

  20. Functional requirements for the man-vehicle systems research facility. [identifying and correcting human errors during flight simulation

    Science.gov (United States)

    Clement, W. F.; Allen, R. W.; Heffley, R. K.; Jewell, W. F.; Jex, H. R.; Mcruer, D. T.; Schulman, T. M.; Stapleford, R. L.

    1980-01-01

    The NASA Ames Research Center proposed a man-vehicle systems research facility to support flight simulation studies which are needed for identifying and correcting the sources of human error associated with current and future air carrier operations. The organization of research facility is reviewed and functional requirements and related priorities for the facility are recommended based on a review of potentially critical operational scenarios. Requirements are included for the experimenter's simulation control and data acquisition functions, as well as for the visual field, motion, sound, computation, crew station, and intercommunications subsystems. The related issues of functional fidelity and level of simulation are addressed, and specific criteria for quantitative assessment of various aspects of fidelity are offered. Recommendations for facility integration, checkout, and staffing are included.

  1. A bridge with a view, a view with a bridge : Identifying design considerations for bridges to strengthen regional identity

    NARCIS (Netherlands)

    Smits, J.E.P.; van der Hoeven, F.D.

    2015-01-01

    This paper discusses design considerations for creating high quality infrastructural artefacts with an emphasis on bridges. The authors pursue a design study and analysis approach to highlight the specifics of infrastructure design for regional identity, based on their own work on a bridge

  2. Aberrant brain regional homogeneity and functional connectivity in middle-aged T2DM patients: a resting-state functional MRI study

    Directory of Open Access Journals (Sweden)

    Daihong Liu

    2016-09-01

    Full Text Available Type 2 diabetes mellitus (T2DM has been associated with cognitive impairment. However, its neurological mechanism remains elusive. Combining regional homogeneity (ReHo and functional connectivity (FC analyses, the present study aimed to investigate brain functional alterations in middle-aged T2DM patients, which could provide complementary information for the neural substrates underlying T2DM-associated brain dysfunction. Twenty-five T2DM patients and 25 healthy controls were involved in neuropsychological testing and structural and resting-state functional magnetic resonance imaging data acquisition. ReHo analysis was conducted to determine the peak coordinates of brain regions with abnormal local brain activity synchronization. Then, the identified brain regions were considered as seeds, and FC between these brain regions and global voxels was computed. Finally, the potential correlations between the imaging indices and neuropsychological data were also explored. Compared with healthy controls, T2DM patients exhibited higher ReHo values in the anterior cingulate gyrus and lower ReHo in right fusiform gyrus, right precentral gyrus and right medial orbit of the superior frontal gyrus. Considering these areas as seed regions, T2DM patients displayed aberrant FC, mainly in the frontal and parietal lobes. The pattern of FC alterations in T2DM patients was characterized by decreased connectivity and positive to negative or negative to positive converted connectivity. Digital Span Test forward scores revealed significant correlations with the ReHo values of the right precentral gyrus (ρ = 0.527, p = 0.014 and FC between the right fusiform gyrus and middle temporal gyrus (ρ = -0.437, p = 0.048. Our findings suggest that T2DM patients suffer from cognitive dysfunction related to spatially local and remote brain activity synchronization impairment. The patterns of ReHo and FC alterations shed light on the mechanisms underlying T2DM-associated brain

  3. Rampant adaptive evolution in regions of proteins with unknown function in Drosophila simulans.

    Directory of Open Access Journals (Sweden)

    Alisha K Holloway

    2007-10-01

    Full Text Available Adaptive protein evolution is pervasive in Drosophila. Genomic studies, thus far, have analyzed each protein as a single entity. However, the targets of adaptive events may be localized to particular parts of proteins, such as protein domains or regions involved in protein folding. We compared the population genetic mechanisms driving sequence polymorphism and divergence in defined protein domains and non-domain regions. Interestingly, we find that non-domain regions of proteins are more frequent targets of directional selection. Protein domains are also evolving under directional selection, but appear to be under stronger purifying selection than non-domain regions. Non-domain regions of proteins clearly play a major role in adaptive protein evolution on a genomic scale and merit future investigations of their functional properties.

  4. Investigations of the regional pulmonary function by means of 133Xe and a multichannel set

    International Nuclear Information System (INIS)

    Tarkowska, A.; Woytowicz, A.; Zaorska-Rajca, J.

    1978-01-01

    The technique of radiospirometric investigation based on a modification of the method described by Ball et al. is reported. The measurements were carried out in sitting position of the patients after intravenous and inhalatory administration of 133 Xe with a four-channel radiological unit for functional investigations. The results of the measurements were recorded in linear scale with a four-channel writer. Frequency of beats was read from these curves and following indices were calculated for each of four tested regions of the lungs: ventilation index, perfusion index, ventilation-perfusion quotient, total pulmonary capacity in a given region in percent of the total capacity of both lungs, residual volume in a given region in percent of the total residual volume of both lungs, vital capacity in a given region in percent of the total vital capacity of both lungs, residual volume in a given region in percent of the total pulmonary capacity in this region, percent one-minute expiration. Variability coefficients of different indices calculated from two determinations in a group of 10 patients with pulmonary diseases were from 2.05 to 5.9%. For illustration of the effectiveness of the method the results of determinations of regional pulmonary function in 10 healthy subjects, a patient with chronic bronchitis and a patient with upper right lobe cirrhosis are presented. (author)

  5. Functional and structural balances of homologous sensorimotor regions in multiple sclerosis fatigue

    DEFF Research Database (Denmark)

    Cogliati Dezza, I; Zito, G; Tomasevic, L

    2015-01-01

    regions-known to be crucial for sensorimotor networks effectiveness-decrease with MS fatigue increase. Functional connectivity measures at rest and during a simple motor task (weak handgrip of either the right or left hand) were derived from primary sensorimotor areas electroencephalographic recordings......Fatigue in multiple sclerosis (MS) is a highly disabling symptom. Among the central mechanisms behind it, an involvement of sensorimotor networks is clearly evident from structural and functional studies. We aimed at assessing whether functional/structural balances of homologous sensorimotor...... in 27 mildly disabled MS patients. Structural MRI-derived inter-hemispheric asymmetries included the cortical thickness of Rolandic regions and the volume of thalami. Fatigue symptoms increased together with the functional inter-hemispheric imbalance of sensorimotor homologous areas activities at rest...

  6. DNA fingerprinting tags novel altered chromosomal regions and identifies the involvement of SOX5 in the progression of prostate cancer.

    Science.gov (United States)

    Ma, Stephanie; Chan, Yuen Piu; Woolcock, Bruce; Hu, Liang; Wong, Kai Yau; Ling, Ming Tat; Bainbridge, Terry; Webber, Douglas; Chan, Tim Hon Man; Guan, Xin-Yuan; Lam, Wan; Vielkind, Juergen; Chan, Kwok Wah

    2009-05-15

    Identification of genomic alterations associated with the progression of prostate cancer may facilitate the better understanding of the development of this highly variable disease. Matched normal, premalignant high-grade prostatic intraepithelial neoplasia and invasive prostate carcinoma cells were procured by laser capture microdissection (LCM) from human radical prostatectomy specimens. From these cells, comparative DNA fingerprints were generated by a modified PCR-based technique called scanning of microdissected archival lesion (SMAL)-PCR. Recurrent polymorphic fingerprint fragments were used in tagging altered chromosomal regions. Altered regions were found at cytobands 1p31.3, 1q44, 2p23.1, 3p26.3, 3q22.3, 4q22.3, 4q35.2, 5q23.2, 8q22.3, 8q24.13, 9q21.3, 9q22.32, 10q11.21, 11p13, 12p12.1, 13q12.1, 16q12.2 and 18q21.31. Candidate genes in the surrounding area that may possibly harbor mutations that change normal prostatic cells to progress into their tumor stages were proposed. Of these fragments, a 420 bp alteration, absent in all 26 normal samples screened, was observed in 2 tumors. This fragment was cloned, sequenced and localized to chromosome 12p12.1. Within this region, candidate gene sex determining region Y-box 5 (SOX5) was proposed. Further studies of SOX5 in cell lines, xenografts and human prostate specimens, at both the RNA and protein levels, found overexpression of the gene in tumors. This overexpression was then subsequently found by fluorescent in situ hybridization to be caused by amplification of the region. In conclusion, our results suggest LCM coupled with SMAL-PCR DNA fingerprinting is a useful method for the screening and identification of chromosomal regions and genes associated with cancer development. Further, overexpression of SOX5 is associated with prostate tumor progression and early development of distant metastasis. (c) 2008 Wiley-Liss, Inc.

  7. Identifying Watershed Regions Sensitive to Soil Erosion and Contributing to Lake Eutrophication—A Case Study in the Taihu Lake Basin (China)

    Science.gov (United States)

    Lin, Chen; Ma, Ronghua; He, Bin

    2015-01-01

    Taihu Lake in China is suffering from severe eutrophication partly due to non-point pollution from the watershed. There is an increasing need to identify the regions within the watershed that most contribute to lake water degradation. The selection of appropriate temporal scales and lake indicators is important to identify sensitive watershed regions. This study selected three eutrophic lake areas, including Meiliang Bay (ML), Zhushan Bay (ZS), and the Western Coastal region (WC), as well as multiple buffer zones next to the lake boundary as the study sites. Soil erosion intensity was designated as a watershed indicator, and the lake algae area was designated as a lake quality indicator. The sensitive watershed region was identified based on the relationship between these two indicators among different lake divisions for a temporal sequence from 2000 to 2012. The results show that the relationship between soil erosion modulus and lake quality varied among different lake areas. Soil erosion from the two bay areas was more closely correlated with water quality than soil erosion from the WC region. This was most apparent at distances of 5 km to 10 km from the lake, where the r2 was as high as 0.764. Results indicate that soil erosion could be used as an indicator for identifying key watershed protection areas. Different lake areas need to be considered separately due to differences in geographical features, land use, and the corresponding effects on lake water quality. PMID:26712772

  8. Identifying Watershed Regions Sensitive to Soil Erosion and Contributing to Lake Eutrophication--A Case Study in the Taihu Lake Basin (China).

    Science.gov (United States)

    Lin, Chen; Ma, Ronghua; He, Bin

    2015-12-24

    Taihu Lake in China is suffering from severe eutrophication partly due to non-point pollution from the watershed. There is an increasing need to identify the regions within the watershed that most contribute to lake water degradation. The selection of appropriate temporal scales and lake indicators is important to identify sensitive watershed regions. This study selected three eutrophic lake areas, including Meiliang Bay (ML), Zhushan Bay (ZS), and the Western Coastal region (WC), as well as multiple buffer zones next to the lake boundary as the study sites. Soil erosion intensity was designated as a watershed indicator, and the lake algae area was designated as a lake quality indicator. The sensitive watershed region was identified based on the relationship between these two indicators among different lake divisions for a temporal sequence from 2000 to 2012. The results show that the relationship between soil erosion modulus and lake quality varied among different lake areas. Soil erosion from the two bay areas was more closely correlated with water quality than soil erosion from the WC region. This was most apparent at distances of 5 km to 10 km from the lake, where the r² was as high as 0.764. Results indicate that soil erosion could be used as an indicator for identifying key watershed protection areas. Different lake areas need to be considered separately due to differences in geographical features, land use, and the corresponding effects on lake water quality.

  9. Summary Report of the Consultants' Meeting on EXFOR Data in Resonance Region and Spectrometer Response Function

    International Nuclear Information System (INIS)

    Gunsing, F.; Schillebeeckx, P.; Semkova, V.

    2013-12-01

    The Consultants' Meeting 'EXFOR Data in Resonance Region and Spectrometer Response Function' was held at the IAEA Headquarters in Vienna from 8 to 10 October 2013. A summary of the presentations and discussions that took place during the meeting is reported here. The participants have agreed on recommendations on data reporting for EXFOR and on the need of documenting spectrometer response functions. Recommendations are given for experimentalists, for compilers, and for evaluators. (author)

  10. Expression and functional assessment of candidate type 2 diabetes susceptibility genes identify four new genes contributing to human insulin secretion

    Directory of Open Access Journals (Sweden)

    Fatou K. Ndiaye

    2017-06-01

    Full Text Available Objectives: Genome-wide association studies (GWAS have identified >100 loci independently contributing to type 2 diabetes (T2D risk. However, translational implications for precision medicine and for the development of novel treatments have been disappointing, due to poor knowledge of how these loci impact T2D pathophysiology. Here, we aimed to measure the expression of genes located nearby T2D associated signals and to assess their effect on insulin secretion from pancreatic beta cells. Methods: The expression of 104 candidate T2D susceptibility genes was measured in a human multi-tissue panel, through PCR-free expression assay. The effects of the knockdown of beta-cell enriched genes were next investigated on insulin secretion from the human EndoC-βH1 beta-cell line. Finally, we performed RNA-sequencing (RNA-seq so as to assess the pathways affected by the knockdown of the new genes impacting insulin secretion from EndoC-βH1, and we analyzed the expression of the new genes in mouse models with altered pancreatic beta-cell function. Results: We found that the candidate T2D susceptibility genes' expression is significantly enriched in pancreatic beta cells obtained by laser capture microdissection or sorted by flow cytometry and in EndoC-βH1 cells, but not in insulin sensitive tissues. Furthermore, the knockdown of seven T2D-susceptibility genes (CDKN2A, GCK, HNF4A, KCNK16, SLC30A8, TBC1D4, and TCF19 with already known expression and/or function in beta cells changed insulin secretion, supporting our functional approach. We showed first evidence for a role in insulin secretion of four candidate T2D-susceptibility genes (PRC1, SRR, ZFAND3, and ZFAND6 with no previous knowledge of presence and function in beta cells. RNA-seq in EndoC-βH1 cells with decreased expression of PRC1, SRR, ZFAND6, or ZFAND3 identified specific gene networks related to T2D pathophysiology. Finally, a positive correlation between the expression of Ins2 and the

  11. Development and Application of a Planning Support System for Regional Spatial Functional Zoning Based on GIS

    Directory of Open Access Journals (Sweden)

    Xiaorui Zhang

    2016-09-01

    Full Text Available Regional spatial functional zoning in China is a large-scale strategic planning and requires very advanced planning decision support technology. With respect to spatial functional zoning, the planning support system (PSS is introduced as one of the most popular computer aided planning systems at the present time in this paper, and is further explained with the example of the latest regional main functional area (RMFA planning in China. On the Visual Studio.NET visualization development platform, the planning decision model, planning decision method, and GIS are organically integrated and customized by using the component-type secondary development technology of the ArcGIS Engine with the development language VB.NET. Hence, a highly efficient and flexible planning support system of regional main functional areas (RMFA-PSS is established. It was adopted in the research of the Beijing–Tianjin area in China and accordingly two types of main functional area planning are acquired. The RMFA-PSS offers an efficient and flexible decision support with regard to RMFA planning. The research can provide a reference for further PSS development and applications related to other types of spatial functional zoning.

  12. ChIPnorm: a statistical method for normalizing and identifying differential regions in histone modification ChIP-seq libraries.

    Science.gov (United States)

    Nair, Nishanth Ulhas; Sahu, Avinash Das; Bucher, Philipp; Moret, Bernard M E

    2012-01-01

    The advent of high-throughput technologies such as ChIP-seq has made possible the study of histone modifications. A problem of particular interest is the identification of regions of the genome where different cell types from the same organism exhibit different patterns of histone enrichment. This problem turns out to be surprisingly difficult, even in simple pairwise comparisons, because of the significant level of noise in ChIP-seq data. In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods. We correlate the histone marks with gene expression data and confirm that histone modifications H3K27me3 and H3K4me3 act as respectively a repressor and an activator of genes. Compared to what was previously reported in the literature, we find that a substantially higher fraction of bivalent marks in ES cells for H3K27me3 and H3K4me3 move into a K27-only state. We find that most of the promoter regions in protein-coding genes have differential histone-modification sites. The software for this work can be downloaded from http://lcbb.epfl.ch/software.html.

  13. Functional network-based statistics in depression: Theory of mind subnetwork and importance of parietal region.

    Science.gov (United States)

    Lai, Chien-Han; Wu, Yu-Te; Hou, Yuh-Ming

    2017-08-01

    The functional network analysis of whole brain is an emerging field for research in depression. We initiated this study to investigate which subnetwork is significantly altered within the functional connectome in major depressive disorder (MDD). The study enrolled 52 first-episode medication-naïve patients with MDD and 40 controls for functional network analysis. All participants received the resting-state functional imaging using a 3-Tesla magnetic resonance scanner. After preprocessing, we calculated the connectivity matrix of functional connectivity in whole brain for each subject. The network-based statistics of connectome was used to perform group comparisons between patients and controls. The correlations between functional connectivity and clinical parameters were also performed. MDD patients had significant alterations in the network involving "theory of mind" regions, such as the left precentral gyrus, left angular gyrus, bilateral rolandic operculums and left inferior frontal gyrus. The center node of significant network was the left angular gyrus. No significant correlations of functional connectivity within the subnetwork and clinical parameters were noted. Functional connectivity of "theory of mind" subnetwork may be the core issue for pathophysiology in MDD. In addition, the center role of parietal region should be emphasized in future study. Copyright © 2017. Published by Elsevier B.V.

  14. Retelling Basic Writing at a Regional Campus: Iconic Discourse and Selective Function Meet Social Class

    Science.gov (United States)

    Tassoni, John Paul

    2005-01-01

    This article relates case histories of basic writing programs at regional campuses in Florida, and the perceived need to incorporate concerns of social class into basic writing curriculum. Attention to class helps scholars identify institutional patterns that distance basic writing from the university's mainstream business. This author describes a…

  15. Profiling of the Tox21 Chemical Collection for Mitochondrial Function to Identify Compounds that Acutely Decrease Mitochondrial Membrane Potential

    Science.gov (United States)

    Attene-Ramos, Matias S.; Huang, Ruili; Michael, Sam; Witt, Kristine L.; Richard, Ann; Tice, Raymond R.; Simeonov, Anton; Austin, Christopher P.

    2014-01-01

    Background: Mitochondrial dysfunction has been implicated in the pathogenesis of a variety of disorders including cancer, diabetes, and neurodegenerative and cardiovascular diseases. Understanding whether different environmental chemicals and druglike molecules impact mitochondrial function represents an initial step in predicting exposure-related toxicity and defining a possible role for such compounds in the onset of various diseases. Objectives: We sought to identify individual chemicals and general structural features associated with changes in mitochondrial membrane potential (MMP). Methods: We used a multiplexed [two end points in one screen; MMP and adenosine triphosphate (ATP) content] quantitative high throughput screening (qHTS) approach combined with informatics tools to screen the Tox21 library of 10,000 compounds (~ 8,300 unique chemicals) at 15 concentrations each in triplicate to identify chemicals and structural features that are associated with changes in MMP in HepG2 cells. Results: Approximately 11% of the compounds (913 unique compounds) decreased MMP after 1 hr of treatment without affecting cell viability (ATP content). In addition, 309 compounds decreased MMP over a concentration range that also produced measurable cytotoxicity [half maximal inhibitory concentration (IC50) in MMP assay/IC50 in viability assay ≤ 3; p Tice RR, Simeonov A, Austin CP, Xia M. 2015. Profiling of the Tox21 chemical collection for mitochondrial function to identify compounds that acutely decrease mitochondrial membrane potential. Environ Health Perspect 123:49–56; http://dx.doi.org/10.1289/ehp.1408642 PMID:25302578

  16. Distinct Molecular Signature of Murine Fetal Liver and Adult Hematopoietic Stem Cells Identify Novel Regulators of Hematopoietic Stem Cell Function.

    Science.gov (United States)

    Manesia, Javed K; Franch, Monica; Tabas-Madrid, Daniel; Nogales-Cadenas, Ruben; Vanwelden, Thomas; Van Den Bosch, Elisa; Xu, Zhuofei; Pascual-Montano, Alberto; Khurana, Satish; Verfaillie, Catherine M

    2017-04-15

    During ontogeny, fetal liver (FL) acts as a major site for hematopoietic stem cell (HSC) maturation and expansion, whereas HSCs in the adult bone marrow (ABM) are largely quiescent. HSCs in the FL possess faster repopulation capacity as compared with ABM HSCs. However, the molecular mechanism regulating the greater self-renewal potential of FL HSCs has not yet extensively been assessed. Recently, we published RNA sequencing-based gene expression analysis on FL HSCs from 14.5-day mouse embryo (E14.5) in comparison to the ABM HSCs. We reanalyzed these data to identify key transcriptional regulators that play important roles in the expansion of HSCs during development. The comparison of FL E14.5 with ABM HSCs identified more than 1,400 differentially expressed genes. More than 200 genes were shortlisted based on the gene ontology (GO) annotation term "transcription." By morpholino-based knockdown studies in zebrafish, we assessed the function of 18 of these regulators, previously not associated with HSC proliferation. Our studies identified a previously unknown role for tdg, uhrf1, uchl5, and ncoa1 in the emergence of definitive hematopoiesis in zebrafish. In conclusion, we demonstrate that identification of genes involved in transcriptional regulation differentially expressed between expanding FL HSCs and quiescent ABM HSCs, uncovers novel regulators of HSC function.

  17. Leveraging Comparative Genomics to Identify and Functionally Characterize Genes Associated with Sperm Phenotypes in Python bivittatus (Burmese Python

    Directory of Open Access Journals (Sweden)

    Kristopher J. L. Irizarry

    2016-01-01

    Full Text Available Comparative genomics approaches provide a means of leveraging functional genomics information from a highly annotated model organism’s genome (such as the mouse genome in order to make physiological inferences about the role of genes and proteins in a less characterized organism’s genome (such as the Burmese python. We employed a comparative genomics approach to produce the functional annotation of Python bivittatus genes encoding proteins associated with sperm phenotypes. We identify 129 gene-phenotype relationships in the python which are implicated in 10 specific sperm phenotypes. Results obtained through our systematic analysis identified subsets of python genes exhibiting associations with gene ontology annotation terms. Functional annotation data was represented in a semantic scatter plot. Together, these newly annotated Python bivittatus genome resources provide a high resolution framework from which the biology relating to reptile spermatogenesis, fertility, and reproduction can be further investigated. Applications of our research include (1 production of genetic diagnostics for assessing fertility in domestic and wild reptiles; (2 enhanced assisted reproduction technology for endangered and captive reptiles; and (3 novel molecular targets for biotechnology-based approaches aimed at reducing fertility and reproduction of invasive reptiles. Additional enhancements to reptile genomic resources will further enhance their value.

  18. Individual Differences in Neural Regions Functionally Related to Real and Imagined Stuttering

    Science.gov (United States)

    Wymbs, Nicholas F.; Ingham, Roger J.; Ingham, Janis C.; Paolini, Katherine E.; Grafton, Scott T.

    2013-01-01

    Recent brain imaging investigations of developmental stuttering show considerable disagreement regarding which regions are related to stuttering. These divergent findings have been mainly derived from group studies. To investigate functional neurophysiology with improved precision, an individual-participant approach (N = 4) using event-related…

  19. Modeling of the Gross Regional Product on the Basis of Production Functions

    Science.gov (United States)

    Sadovin, Nikolay S.; Kokotkina, Tatiana N.; Barkalova, Tatiana G.; Tsaregorodsev, Evgeny I.

    2016-01-01

    The article is devoted to elaboration and construction of a static model of macroeconomics in which economics is considered as an unstructured holistic unit, the input of which receives the resources, and the output is the result of the functioning of economics in the form of gross domestic product or gross regional product. Resources are…

  20. Muscle Hyperalgesia Correlates With Motor Function in Complex Regional Pain Syndrome Type 1

    NARCIS (Netherlands)

    van Rooijen, Diana E.; Marinus, Johan; Schouten, Alfred Christiaan; Noldus, Lucas P.J.J.; van Hilten, Jacobus J.

    2013-01-01

    At present it is unclear if disturbed sensory processing plays a role in the development of the commonly observed motor impairments in patients with complex regional pain syndrome (CRPS). This study aims to investigate the relation between sensory and motor functioning in CRPS patients with and

  1. Regional differences of physiological functions and cancer susceptibility in the human large intestine

    NARCIS (Netherlands)

    Cats, A; DeVries, EGE; Mulder, NH; Kleibeuker, JH

    1996-01-01

    Regional differences in function, metabolism and morphology between proximal colon, distal colon and rectum may be important in the pathogenesis and biologic behaviour of tumours originating from these segments. Thus, the effect of primary prevention of colorectal cancer may also differ from one

  2. On the absolute stability regions corresponding to partial sums of the exponential function

    KAUST Repository

    Ketcheson, David I.

    2013-12-03

    Certain numerical methods for initial value problems have as stability function the nth partial sum of the exponential function. We study the stability region, i.e., the set in the complex plane over which the nth partial sum has at most unit modulus. It is known that the asymptotic shape of the part of the stability region in the left half-plane is a semi-disk. We quantify this by providing disks that enclose or are enclosed by the stability region or its left half-plane part. The radius of the smallest disk centered at the origin that contains the stability region (or its portion in the left half-plane) is determined for 1 n 20. Bounds on such radii are proved for n 2; these bounds are shown to be optimal in the limit n ! +1. We prove that the stability region and its complement, restricted to the imaginary axis, consist of alternating intervals of length tending to , as n ! 1. Finally, we prove that a semi-disk in the left half-plane with vertical boundary being the imaginary axis and centered at the origin is included in the stability region if and only if n 0 mod 4 or n 3 mod 4. The maximal radii of such semi-disks are exactly determined for 1 n 20.

  3. Genome-wide association study of intraocular pressure identifies the GLCCI1/ICA1 region as a glaucoma susceptibility locus

    OpenAIRE

    Strange, Amy; Bellenguez, Céline; Sim, Xueling; Luben, Robert; Hysi, Pirro G.; Ramdas, Wishal D.; van Koolwijk, Leonieke M.E.; Freeman, Colin; Pirinen, Matti; Su, Zhan; Band, Gavin; Pearson, Richard; Vukcevic, Damjan; Langford, Cordelia; Deloukas, Panos

    2013-01-01

    To discover quantitative trait loci for intraocular pressure, a major risk factor for glaucoma and the only modifiable one, we performed a genome-wide association study on a discovery cohort of 2175 individuals from Sydney, Australia. We found a novel association between intraocular pressure and a common variant at 7p21 near to GLCCI1 and ICA1. The findings in this region were confirmed through two UK replication cohorts totalling 4866 individuals (rs59072263, P(combined) = 1.10 × 10(-8)). A ...

  4. Distinguishing patients with Parkinson's disease subtypes from normal controls based on functional network regional efficiencies.

    Directory of Open Access Journals (Sweden)

    Delong Zhang

    Full Text Available Many studies have demonstrated that the pathophysiology and clinical symptoms of Parkinson's disease (PD are inhomogeneous. However, the symptom-specific intrinsic neural activities underlying the PD subtypes are still not well understood. Here, 15 tremor-dominant PD patients, 10 non-tremor-dominant PD patients, and 20 matched normal controls (NCs were recruited and underwent resting-state functional magnetic resonance imaging (fMRI. Functional brain networks were constructed based on randomly generated anatomical templates with and without the cerebellum. The regional network efficiencies (i.e., the local and global efficiencies were further measured and used to distinguish subgroups of PD patients (i.e., with tremor-dominant PD and non-tremor-dominant PD from the NCs using linear discriminant analysis. The results demonstrate that the subtype-specific functional networks were small-world-organized and that the network regional efficiency could discriminate among the individual PD subgroups and the NCs. Brain regions involved in distinguishing between the study groups included the basal ganglia (i.e., the caudate and putamen, limbic regions (i.e., the hippocampus and thalamus, the cerebellum, and other cerebral regions (e.g., the insula, cingulum, and calcarine sulcus. In particular, the performances of the regional local efficiency in the functional network were better than those of the global efficiency, and the performances of global efficiency were dependent on the inclusion of the cerebellum in the analysis. These findings provide new evidence for the neurological basis of differences between PD subtypes and suggest that the cerebellum may play different roles in the pathologies of different PD subtypes. The present study demonstrated the power of the combination of graph-based network analysis and discrimination analysis in elucidating the neural basis of different PD subtypes.

  5. Novel subgroups of attention-deficit/hyperactivity disorder identified by topological data analysis and their functional network modular organizations.

    Science.gov (United States)

    Kyeong, Sunghyon; Kim, Jae-Jin; Kim, Eunjoo

    2017-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a clinically heterogeneous condition and identification of clinically meaningful subgroups would open up a new window for personalized medicine. Thus, we aimed to identify new clinical phenotypes in children and adolescents with ADHD and to investigate whether neuroimaging findings validate the identified phenotypes. Neuroimaging and clinical data from 67 children with ADHD and 62 typically developing controls (TDCs) from the ADHD-200 database were selected. Clinical measures of ADHD symptoms and intelligence quotient (IQ) were used as input features into a topological data analysis (TDA) to identify ADHD subgroups within our sample. As external validators, graph theoretical measures obtained from the functional connectome were compared to address the biological meaningfulness of the identified subtypes. The TDA identified two unique subgroups of ADHD, labelled as mild symptom ADHD (mADHD) and severe symptom ADHD (sADHD). The output topology shape was repeatedly observed in the independent validation dataset. The graph theoretical analysis showed a decrease in the degree centrality and PageRank in the bilateral posterior cingulate cortex in the sADHD group compared with the TDC group. The mADHD group showed similar patterns of intra- and inter-module connectivity to the sADHD group. Relative to the TDC group, the inter-module connectivity between the default mode network and executive control network were significantly increased in the sADHD group but not in the mADHD group. Taken together, our results show that the data-driven TDA is potentially useful in identifying objective and biologically relevant disease phenotypes in children and adolescents with ADHD.

  6. Novel subgroups of attention-deficit/hyperactivity disorder identified by topological data analysis and their functional network modular organizations.

    Directory of Open Access Journals (Sweden)

    Sunghyon Kyeong

    Full Text Available Attention-deficit/hyperactivity disorder (ADHD is a clinically heterogeneous condition and identification of clinically meaningful subgroups would open up a new window for personalized medicine. Thus, we aimed to identify new clinical phenotypes in children and adolescents with ADHD and to investigate whether neuroimaging findings validate the identified phenotypes. Neuroimaging and clinical data from 67 children with ADHD and 62 typically developing controls (TDCs from the ADHD-200 database were selected. Clinical measures of ADHD symptoms and intelligence quotient (IQ were used as input features into a topological data analysis (TDA to identify ADHD subgroups within our sample. As external validators, graph theoretical measures obtained from the functional connectome were compared to address the biological meaningfulness of the identified subtypes. The TDA identified two unique subgroups of ADHD, labelled as mild symptom ADHD (mADHD and severe symptom ADHD (sADHD. The output topology shape was repeatedly observed in the independent validation dataset. The graph theoretical analysis showed a decrease in the degree centrality and PageRank in the bilateral posterior cingulate cortex in the sADHD group compared with the TDC group. The mADHD group showed similar patterns of intra- and inter-module connectivity to the sADHD group. Relative to the TDC group, the inter-module connectivity between the default mode network and executive control network were significantly increased in the sADHD group but not in the mADHD group. Taken together, our results show that the data-driven TDA is potentially useful in identifying objective and biologically relevant disease phenotypes in children and adolescents with ADHD.

  7. Disease-associated mutations identify a novel region in human STING necessary for the control of type I interferon signaling

    OpenAIRE

    Melki, Isabelle; Rose, Yoann; Uggenti, Carolina; Van Eyck, Lien; Frémond, Marie-Louise; Kitabayashi, Naoki; Rice, Gillian I; Jenkinson, Emma M; Boulai, Anaïs; Jeremiah, Nadia; Gattorno, Marco; Volpi, Sefano; Sacco, Olivero; Terheggen-Lagro, Suzanne W J; Tiddens, Harm A W M

    2017-01-01

    BACKGROUND: Gain-of-function mutations in transmembrane protein 173 (TMEM173) encoding stimulator of interferon genes (STING) underlie a recently described type I interferonopathy called STING-associated vasculopathy with onset in infancy (SAVI).OBJECTIVES: We sought to define the molecular and cellular pathology relating to 3 individuals variably exhibiting the core features of the SAVI phenotype including systemic inflammation, destructive skin lesions, and interstitial lung disease.METHODS...

  8. SVD identifies transcript length distribution functions from DNA microarray data and reveals evolutionary forces globally affecting GBM metabolism.

    Directory of Open Access Journals (Sweden)

    Nicolas M Bertagnolli

    Full Text Available To search for evolutionary forces that might act upon transcript length, we use the singular value decomposition (SVD to identify the length distribution functions of sets and subsets of human and yeast transcripts from profiles of mRNA abundance levels across gel electrophoresis migration distances that were previously measured by DNA microarrays. We show that the SVD identifies the transcript length distribution functions as "asymmetric generalized coherent states" from the DNA microarray data and with no a-priori assumptions. Comparing subsets of human and yeast transcripts of the same gene ontology annotations, we find that in both disparate eukaryotes, transcripts involved in protein synthesis or mitochondrial metabolism are significantly shorter than typical, and in particular, significantly shorter than those involved in glucose metabolism. Comparing the subsets of human transcripts that are overexpressed in glioblastoma multiforme (GBM or normal brain tissue samples from The Cancer Genome Atlas, we find that GBM maintains normal brain overexpression of significantly short transcripts, enriched in transcripts that are involved in protein synthesis or mitochondrial metabolism, but suppresses normal overexpression of significantly longer transcripts, enriched in transcripts that are involved in glucose metabolism and brain activity. These global relations among transcript length, cellular metabolism and tumor development suggest a previously unrecognized physical mode for tumor and normal cells to differentially regulate metabolism in a transcript length-dependent manner. The identified distribution functions support a previous hypothesis from mathematical modeling of evolutionary forces that act upon transcript length in the manner of the restoring force of the harmonic oscillator.

  9. Evaluation of regional pulmonary function using short-lived radioactive gases

    Energy Technology Data Exchange (ETDEWEB)

    Ashitaka, Tsuyoshi [Toho Univ., Tokyo (Japan). School of Medicine

    1993-05-01

    We investigated the application of short-lived radioactive gases for the assessment of regional pulmonary function, particularly diffusing capacity, in patients with chronic obstructive lung disease and interstitial lung disease. Short-lived radioactive gases including C[sup 15]O-O, [sup 11]CO[sub 2], and [sup 11]CO were produced using a baby cyclotron for medical care. Using a [gamma] camera, breath-holding images were taken serially after inhalation of the radioactive gases. The first exponential component of time-activity curve was analyzed to obtain clearance rate, which was expressed as exponential coefficient ([lambda]). Moreover, we created a functional map which was calculated by the clearance rate of [sup 11]CO[sub 2] as a percentage. Regional clearance rates of each gas in normal volunteers revealed higher values in the lower lung field than in the upper lung field. Whole lung clearance rates ([lambda]) of each gas in patients correlated well with D[sub LCO]/V[sub A], which indicates diffusing capacity. The functional map showed decreased regional diffusion closely matched to the perfusion defects seen by [sup 99m]Tc-MAA perfusion images. However, in certain interstitial lung diseases decreased clearance of [sup 11]CO[sub 2] was observed in regions having no evidence of perfusion defects. We concluded the functional map display of [sup 11]CO[sub 2] is useful indicator of the regional diffusing capacity of both the normal and diseased lung, and that it is beneficial to analyze the pathogenic physiology of diseased lungs by making a comparison between the functional map of [sup 11]CO[sub 2] and [sup 99m]Tc-MAA perfusion images. (author).

  10. The cross-functional role of frontoparietal regions in cognition: internal attention as the overarching mechanism.

    Science.gov (United States)

    Lückmann, Helen C; Jacobs, Heidi I L; Sack, Alexander T

    2014-05-01

    Neuroimaging studies have repeatedly reported findings of activation in frontoparietal regions that largely overlap across various cognitive functions. Part of this frontoparietal activation has been interpreted as reflecting attentional mechanisms that can adaptively be directed towards external stimulation as well as internal representations (internal attention), thereby generating the experience of distinct cognitive functions. Nevertheless, findings of material- and task-specific activation in frontal and parietal regions challenge this internal attention hypothesis and have been used to support more modular hypotheses of cognitive function. The aim of this review is twofold: First, it discusses evidence in support of the concept of internal attention and the so-called dorsal attention network (DAN) as its neural source with respect to three cognitive functions (working memory, episodic retrieval, and mental imagery). While DAN activation in all three functions has been separately linked to internal attention, a comprehensive and integrative review has so far been lacking. Second, the review examines findings of material- and process-specific activation within frontoparietal regions, arguing that these results are well compatible with the internal attention account of frontoparietal activation. A new model of cognition is presented, proposing that supposedly different cognitive concepts actually rely on similar attentional network dynamics to maintain, reactivate and newly create internal representations of stimuli in various modalities. Attentional as well as representational mechanisms are assigned to frontal and parietal regions, positing that some regions are implicated in the allocation of attentional resources to perceptual or internal representations, but others are involved in the representational processes themselves. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Relating genes to function: identifying enriched transcription factors using the ENCODE ChIP-Seq significance tool.

    Science.gov (United States)

    Auerbach, Raymond K; Chen, Bin; Butte, Atul J

    2013-08-01

    Biological analysis has shifted from identifying genes and transcripts to mapping these genes and transcripts to biological functions. The ENCODE Project has generated hundreds of ChIP-Seq experiments spanning multiple transcription factors and cell lines for public use, but tools for a biomedical scientist to analyze these data are either non-existent or tailored to narrow biological questions. We present the ENCODE ChIP-Seq Significance Tool, a flexible web application leveraging public ENCODE data to identify enriched transcription factors in a gene or transcript list for comparative analyses. The ENCODE ChIP-Seq Significance Tool is written in JavaScript on the client side and has been tested on Google Chrome, Apple Safari and Mozilla Firefox browsers. Server-side scripts are written in PHP and leverage R and a MySQL database. The tool is available at http://encodeqt.stanford.edu. abutte@stanford.edu Supplementary material is available at Bioinformatics online.

  12. Financial literacy is associated with medial brain region functional connectivity in old age.

    Science.gov (United States)

    Han, S Duke; Boyle, Patricia A; Yu, Lei; Fleischman, Debra A; Arfanakis, Konstantinos; Leurgans, Sue; Bennett, David A

    2014-01-01

    Financial literacy refers to the ability to access and utilize financial information in ways that promote better outcomes. In old age, financial literacy has been associated with a wide range of positive characteristics; however, the neural correlates remain unclear. Recent work has suggested greater co-activity between anterior-posterior medial brain regions is associated with better brain functioning. We hypothesized financial literacy would be associated with this pattern. We assessed whole-brain functional connectivity to a posterior cingulate cortex (PCC) seed region of interest (ROI) in 138 participants of the Rush Memory and Aging Project. Results revealed financial literacy was associated with greater functional connectivity between the PCC and three regions: the right ventromedial prefrontal cortex (vmPFC), the left postcentral gyrus, and the right precuneus. Results also revealed financial literacy was associated negatively with functional connectivity between the PCC and left caudate. Post hoc analyses showed the PCC-vmPFC relationship accounted for the most variance in a regression model adjusted for all four significant functional connectivity relationships, demographic factors, and global cognition. These findings provide information on the neural mechanisms associated with financial literacy in old age. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. FishVis, A regional decision support tool for identifying vulnerabilities of riverine habitat and fishes to climate change in the Great Lakes Region

    Science.gov (United States)

    Stewart, Jana S.; Covert, S. Alex; Estes, Nick J.; Westenbroek, Stephen M.; Krueger, Damon; Wieferich, Daniel J.; Slattery, Michael T.; Lyons, John D.; McKenna, James E.; Infante, Dana M.; Bruce, Jennifer L.

    2016-10-13

    Climate change is expected to alter the distributions and community composition of stream fishes in the Great Lakes region in the 21st century, in part as a result of altered hydrological systems (stream temperature, streamflow, and habitat). Resource managers need information and tools to understand where fish species and stream habitats are expected to change under future conditions. Fish sample collections and environmental variables from multiple sources across the United States Great Lakes Basin were integrated and used to develop empirical models to predict fish species occurrence under present-day climate conditions. Random Forests models were used to predict the probability of occurrence of 13 lotic fish species within each stream reach in the study area. Downscaled climate data from general circulation models were integrated with the fish species occurrence models to project fish species occurrence under future climate conditions. The 13 fish species represented three ecological guilds associated with water temperature (cold, cool, and warm), and the species were distributed in streams across the Great Lakes region. Vulnerability (loss of species) and opportunity (gain of species) scores were calculated for all stream reaches by evaluating changes in fish species occurrence from present-day to future climate conditions. The 13 fish species included 4 cold-water species, 5 cool-water species, and 4 warm-water species. Presently, the 4 cold-water species occupy from 15 percent (55,000 kilometers [km]) to 35 percent (130,000 km) of the total stream length (369,215 km) across the study area; the 5 cool-water species, from 9 percent (33,000 km) to 58 percent (215,000 km); and the 4 warm-water species, from 9 percent (33,000 km) to 38 percent (141,000 km).Fish models linked to projections from 13 downscaled climate models projected that in the mid to late 21st century (2046–65 and 2081–2100, respectively) habitats suitable for all 4 cold-water species and 4

  14. Regional variation in the structure and function of parrotfishes on Arabian reefs

    KAUST Repository

    Hoey, Andrew

    2015-11-20

    Parrotfishes (f. Labridae) are a unique and ubiquitous group of herbivorous reef fishes. We compared the distribution and ecosystem function (grazing and erosion) of parrotfishes across 75 reefs in Arabia. Our results revealed marked regional differences in the abundance, and taxonomic and functional composition of parrotfishes between the Red Sea, Arabian Sea, and Arabian Gulf. High densities and diversity of parrotfishes, and high rates of grazing (210% year) and erosion (1.57 kg m year) characterised Red Sea reefs. Despite Arabian Sea and Red Sea reefs having broadly comparable abundances of parrotfishes, estimates of grazing (150% year) and erosion (0.43 kg m year) were markedly lower in the Arabian Sea. Parrotfishes were extremely rare within the southern Arabian Gulf, and as such rates of grazing and erosion were negligible. This regional variation in abundance and functional composition of parrotfishes appears to be related to local environmental conditions.

  15. Mining the Human Complexome Database Identifies RBM14 as an XPO1-Associated Protein Involved in HIV-1 Rev Function

    OpenAIRE

    Budhiraja, Sona; Liu, Hongbing; Couturier, Jacob; Malovannaya, Anna; Qin, Jun; Lewis, Dorothy E.; Rice, Andrew P.

    2015-01-01

    By recruiting the host protein XPO1 (CRM1), the HIV-1 Rev protein mediates the nuclear export of incompletely spliced viral transcripts. We mined data from the recently described human nuclear complexome to identify a host protein, RBM14, which associates with XPO1 and Rev and is involved in Rev function. Using a Rev-dependent p24 reporter plasmid, we found that RBM14 depletion decreased Rev activity and Rev-mediated enhancement of the cytoplasmic levels of unspliced viral transcripts. RBM14 ...

  16. Regional specific groundwater arsenic levels and neuropsychological functioning: a cross-sectional study.

    Science.gov (United States)

    Edwards, Melissa; Johnson, Leigh; Mauer, Cortney; Barber, Robert; Hall, James; O'Bryant, Sid

    2014-01-01

    The purpose of the study was to examine the link between geographic information system (GIS)-estimated regional specific groundwater levels and neuropsychological functioning in a sample of individuals with and without cognitive impairment. This cross-sectional study design analyzed data from 1390 participants (733 Alzheimer's disease, 127 Mild Cognitive Impairment, and 530 with normal cognition) enrolled in the Texas Alzheimer's Research and Care Consortium. GISs analyses were used to estimate regional specific groundwater arsenic concentrations using the Environmental Systems Research Institute and arsenic concentrations from the Texas Water Development Board. In the full cohort, regional specific arsenic concentrations were positively associated with language abilities (p = 0.008), but associated with poorer verbal memory, immediate (p = 0.008), and delayed (p arsenic being related with cognition most prominently among mild cognitive impairment cases. Overall, estimated regional specific groundwater arsenic levels were negatively associated with neuropsychological performance.

  17. Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors.

    Science.gov (United States)

    Olson, William; Abdus-Saboor, Ishmail; Cui, Lian; Burdge, Justin; Raabe, Tobias; Ma, Minghong; Luo, Wenqin

    2017-10-12

    The human distal limbs have a high spatial acuity for noxious stimuli but a low density of pain-sensing neurites. To elucidate mechanisms underlying regional differences in processing nociception, we sparsely traced non-peptidergic nociceptors across the body using a newly generated Mrgprd CreERT2 mouse line. We found that mouse plantar paw skin is also innervated by a low density of Mrgprd + nociceptors, while individual arbors in different locations are comparable in size. Surprisingly, the central arbors of plantar paw and trunk innervating nociceptors have distinct morphologies in the spinal cord. This regional difference is well correlated with a heightened signal transmission for plantar paw circuits, as revealed by both spinal cord slice recordings and behavior assays. Taken together, our results elucidate a novel somatotopic functional organization of the mammalian pain system and suggest that regional central arbor structure could facilitate the "enlarged representation" of plantar paw regions in the CNS.

  18. Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies

    Science.gov (United States)

    Zhang, Shujun

    2018-01-01

    Genome-wide association studies (GWASs) have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART). With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study. PMID:29377896

  19. Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Xingjie Hao

    2018-01-01

    Full Text Available Genome-wide association studies (GWASs have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART. With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study.

  20. Cross-Modal Functional Reorganization of Visual and Auditory Cortex in Adult Cochlear Implant Users Identified with fNIRS.

    Science.gov (United States)

    Chen, Ling-Chia; Sandmann, Pascale; Thorne, Jeremy D; Bleichner, Martin G; Debener, Stefan

    2016-01-01

    Cochlear implant (CI) users show higher auditory-evoked activations in visual cortex and higher visual-evoked activation in auditory cortex compared to normal hearing (NH) controls, reflecting functional reorganization of both visual and auditory modalities. Visual-evoked activation in auditory cortex is a maladaptive functional reorganization whereas auditory-evoked activation in visual cortex is beneficial for speech recognition in CI users. We investigated their joint influence on CI users' speech recognition, by testing 20 postlingually deafened CI users and 20 NH controls with functional near-infrared spectroscopy (fNIRS). Optodes were placed over occipital and temporal areas to measure visual and auditory responses when presenting visual checkerboard and auditory word stimuli. Higher cross-modal activations were confirmed in both auditory and visual cortex for CI users compared to NH controls, demonstrating that functional reorganization of both auditory and visual cortex can be identified with fNIRS. Additionally, the combined reorganization of auditory and visual cortex was found to be associated with speech recognition performance. Speech performance was good as long as the beneficial auditory-evoked activation in visual cortex was higher than the visual-evoked activation in the auditory cortex. These results indicate the importance of considering cross-modal activations in both visual and auditory cortex for potential clinical outcome estimation.

  1. Cross-Modal Functional Reorganization of Visual and Auditory Cortex in Adult Cochlear Implant Users Identified with fNIRS

    Directory of Open Access Journals (Sweden)

    Ling-Chia Chen

    2016-01-01

    Full Text Available Cochlear implant (CI users show higher auditory-evoked activations in visual cortex and higher visual-evoked activation in auditory cortex compared to normal hearing (NH controls, reflecting functional reorganization of both visual and auditory modalities. Visual-evoked activation in auditory cortex is a maladaptive functional reorganization whereas auditory-evoked activation in visual cortex is beneficial for speech recognition in CI users. We investigated their joint influence on CI users’ speech recognition, by testing 20 postlingually deafened CI users and 20 NH controls with functional near-infrared spectroscopy (fNIRS. Optodes were placed over occipital and temporal areas to measure visual and auditory responses when presenting visual checkerboard and auditory word stimuli. Higher cross-modal activations were confirmed in both auditory and visual cortex for CI users compared to NH controls, demonstrating that functional reorganization of both auditory and visual cortex can be identified with fNIRS. Additionally, the combined reorganization of auditory and visual cortex was found to be associated with speech recognition performance. Speech performance was good as long as the beneficial auditory-evoked activation in visual cortex was higher than the visual-evoked activation in the auditory cortex. These results indicate the importance of considering cross-modal activations in both visual and auditory cortex for potential clinical outcome estimation.

  2. Novel immune-modulator identified by a rapid, functional screen of the parapoxvirus ovis (Orf virus genome

    Directory of Open Access Journals (Sweden)

    McGuire Michael J

    2012-01-01

    Full Text Available Abstract Background The success of new sequencing technologies and informatic methods for identifying genes has made establishing gene product function a critical rate limiting step in progressing the molecular sciences. We present a method to functionally mine genomes for useful activities in vivo, using an unusual property of a member of the poxvirus family to demonstrate this screening approach. Results The genome of Parapoxvirus ovis (Orf virus was sequenced, annotated, and then used to PCR-amplify its open-reading-frames. Employing a cloning-independent protocol, a viral expression-library was rapidly built and arrayed into sub-library pools. These were directly delivered into mice as expressible cassettes and assayed for an immune-modulating activity associated with parapoxvirus infection. The product of the B2L gene, a homolog of vaccinia F13L, was identified as the factor eliciting immune cell accumulation at sites of skin inoculation. Administration of purified B2 protein also elicited immune cell accumulation activity, and additionally was found to serve as an adjuvant for antigen-specific responses. Co-delivery of the B2L gene with an influenza gene-vaccine significantly improved protection in mice. Furthermore, delivery of the B2L expression construct, without antigen, non-specifically reduced tumor growth in murine models of cancer. Conclusion A streamlined, functional approach to genome-wide screening of a biological activity in vivo is presented. Its application to screening in mice for an immune activity elicited by the pathogen genome of Parapoxvirus ovis yielded a novel immunomodulator. In this inverted discovery method, it was possible to identify the adjuvant responsible for a function of interest prior to a mechanistic study of the adjuvant. The non-specific immune activity of this modulator, B2, is similar to that associated with administration of inactivated particles to a host or to a live viral infection. Administration

  3. Use of DNA sequences to identify forensically important fly species and their distribution in the coastal region of Central California.

    Science.gov (United States)

    Nakano, Angie; Honda, Jeff

    2015-08-01

    Forensic entomology has gained prominence in recent years, as improvements in DNA technology and molecular methods have allowed insect and other arthropod evidence to become increasingly useful in criminal and civil investigations. However, comprehensive faunal inventories are still needed, including cataloging local DNA sequences for forensically significant Diptera. This multi-year fly-trapping study was built upon and expanded a previous survey of these flies in Santa Clara County, including the addition of genetic barcoding data from collected species of flies. Flies from the families Calliphoridae, Sarcophagidae, and Muscidae were trapped in meat-baited traps set in a variety of locations throughout the county. Flies were identified using morphological features and confirmed by molecular analysis. A total of 16 calliphorid species, 11 sarcophagid species, and four muscid species were collected and differentiated. This study found more species of flies than previous area surveys and established new county records for two calliphorid species: Cynomya cadaverina and Chrysomya rufifacies. Differences were found in fly fauna in different areas of the county, indicating the importance of microclimates in the distribution of these flies. Molecular analysis supported the use of DNA barcoding as an effective method of identifying cryptic fly species. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Serum glycine is associated with regional body fat and insulin resistance in functionally-limited older adults.

    Directory of Open Access Journals (Sweden)

    Michael S Lustgarten

    Full Text Available Metabolic profiling may provide insight into biologic mechanisms related to age-related increases in regional adiposity and insulin resistance.The objectives of the current study were to characterize the association between mid-thigh intermuscular and subcutaneous adipose tissue (IMAT, SCAT, respectively and, abdominal adiposity with the serum metabolite profile, to identify significant metabolites as further associated with the homeostasis model assessment of insulin resistance (HOMA-IR, and, to develop a HOMA-IR associated metabolite predictor set representative of regional adiposity, in 73 functionally-limited (short physical performance battery ≤10; SPPB older adults (age range, 70-85 y.Fasting levels of 181 total metabolites, including amino acids, fatty acids and acylcarnitines were measured with use of an untargeted mass spectrometry-based metabolomic approach. Multivariable-adjusted linear regression was used in all analyses.Thirty-two, seven and one metabolite(s were found to be associated with IMAT, abdominal adiposity and, SCAT, respectively, including the amino acid glycine, which was positively associated with SCAT and, negatively associated with both IMAT and abdominal adiposity. Glycine and four metabolites found to be significantly associated with regional adiposity were additionally associated with HOMA-IR. Separate stepwise regression models identified glycine as a HOMA-IR associated marker of both IMAT (model R(2 = 0.51, p<0.0001 and abdominal adiposity (model R(2 = 0.41, p<0.0001.Our findings for a positive association between glycine with SCAT but, a negative association between glycine with IMAT and abdominal adiposity supports the hypothesis that SCAT metabolic processes are different from that found in other fat depots. In addition, because of the significant associations found between glycine with HOMA-IR, IMAT, SCAT and abdominal adiposity, our results suggest glycine as a serum biomarker of both insulin sensitivity

  5. Disease-associated mutations identify a novel region in human STING necessary for the control of type I interferon signaling.

    Science.gov (United States)

    Melki, Isabelle; Rose, Yoann; Uggenti, Carolina; Van Eyck, Lien; Frémond, Marie-Louise; Kitabayashi, Naoki; Rice, Gillian I; Jenkinson, Emma M; Boulai, Anaïs; Jeremiah, Nadia; Gattorno, Marco; Volpi, Sefano; Sacco, Olivero; Terheggen-Lagro, Suzanne W J; Tiddens, Harm A W M; Meyts, Isabelle; Morren, Marie-Anne; De Haes, Petra; Wouters, Carine; Legius, Eric; Corveleyn, Anniek; Rieux-Laucat, Frederic; Bodemer, Christine; Callebaut, Isabelle; Rodero, Mathieu P; Crow, Yanick J

    2017-08-01

    Gain-of-function mutations in transmembrane protein 173 (TMEM173) encoding stimulator of interferon genes (STING) underlie a recently described type I interferonopathy called STING-associated vasculopathy with onset in infancy (SAVI). We sought to define the molecular and cellular pathology relating to 3 individuals variably exhibiting the core features of the SAVI phenotype including systemic inflammation, destructive skin lesions, and interstitial lung disease. Genetic analysis, conformational studies, in vitro assays and ex vivo flow-cytometry were performed. Molecular and in vitro data demonstrate that the pathology in these patients is due to amino acid substitutions at positions 206, 281, and 284 of the human STING protein. These mutations confer cGAMP-independent constitutive activation of type I interferon signaling through TBK1 (TANK-binding kinase), independent from the alternative STING pathway triggered by membrane fusion of enveloped RNA viruses. This constitutive activation was abrogated by ex vivo treatment with the janus kinase 1/2 inhibitor ruxolitinib. Structural analysis indicates that the 3 disease-associated mutations at positions 206, 281, and 284 of the STING protein define a novel cluster of amino acids with functional importance in the regulation of type I interferon signaling. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Identifying optimal regional solid waste management strategies through an inexact integer programming model containing infinite objectives and constraints.

    Science.gov (United States)

    He, Li; Huang, Guo-He; Zeng, Guang-Ming; Lu, Hong-Wei

    2009-01-01

    The previous inexact mixed-integer linear programming (IMILP) method can only tackle problems with coefficients of the objective function and constraints being crisp intervals, while the existing inexact mixed-integer semi-infinite programming (IMISIP) method can only deal with single-objective programming problems as it merely allows the number of constraints to be infinite. This study proposes, an inexact mixed-integer bi-infinite programming (IMIBIP) method by incorporating the concept of functional intervals into the programming framework. Different from the existing methods, the IMIBIP can tackle the inexact programming problems that contain both infinite objectives and constraints. The developed method is applied to capacity planning of waste management systems under a variety of uncertainties. Four scenarios are considered for comparing the solutions of IMIBIP with those of IMILP. The results indicate that reasonable solutions can be generated by the IMIBIP method. Compared with IMILP, the system cost from IMIBIP would be relatively high since the fluctuating market factors are considered; however, the IMILP solutions are associated with a raised system reliability level and a reduced constraint violation risk level.

  7. Properties of Gribov region and horizon function in the SU(N) Maximal Abelian Gauge

    International Nuclear Information System (INIS)

    Capri, Marcio Andre Lopes; Gomez, A.J.; Guimaraes, M.S.; Lemes, Vitor Emanuel Rodino; Sorella, Silvio Paolo

    2011-01-01

    Full text: The problem of the Gribov copies deals with the impossibility of to choose a unique gauge condition in the quantization process in the Yang Mills theories. In the Landau gauge, several properties of the Gribov region are established, the implementation of the Gribov copies in the path integral is taking account by the introduction of the horizon function directly in the action giving rise to modifications in the ghost and gluon propagator in the infrared regime. However, is interesting to looking at other gauge choices for obtain additional information of the phenomena, and compare our results in the landau gauge. In this work we address the issue of the Gribov copies in SU(N),N ¿ 2, Euclidean Yang-Mills theories quantized in the maximal Abelian gauge. A few properties of the Gribov region in this gauge are established. Similarly to the case of SU(2), the Gribov region turns out to be convex, bounded along the off-diagonals directions in field space, and unbounded along the diagonal ones. The implementation of the restriction to the Gribov region in the functional integral is discussed through the introduction of the horizon function, whose construction will be outlined in detail. The influence of this restriction on the behavior of the gluon and ghost propagators of the theory is also investigated together with a set of dimension two condensates. (author)

  8. Testing peat humification analysis in an Australian context: identifying wet shifts in regional climate over the past 4000 years

    Directory of Open Access Journals (Sweden)

    M.A. Burrows

    2014-08-01

    Full Text Available Peat humification analysis is presented as a robust palaeoclimatic proxy, suitable for use on mid–late Holocene peat sequences situated in the Southern Hemisphere. The proxy is shown to permit the identification of wet and dry shifts in a peat sequence from the humid tropics of north-eastern Australia. A significant correlation is found between the humification record and other proxies indicative of past climate conditions such as pollen, δ13C, C/N and macrocharcoal. Sixteen wet shifts detected in the humification record for Bromfield Swamp occur at the following dates (with 2σ range: 3830 (3920–3740, 3560 (3640–3480, 3490 (3560–3420, 3380 (3450–3300, 3120 (3250–2970, 2950 (3100–2790, 2560 (2710–2450, 2430 (2600–2260, 2120 (2330–1910, 1750 (1980–1520, 1430 (1660–1200, 1170 (1390–960, 1010 (1220–820, 620 (770–500, 300 (400–200 and 100 (200–10 cal. yr BP. Eleven dry shifts are also identified in the record at 4220 (4330–4110, 3670 (3750–3590, 3330 (3420–3220, 3020 (3170–2870, 2350 (2530–2160, 2020 (2230–1800, 1730 (1980–1510, 1290 (1510–1070, 700 (870–560, 400 (470–300 and 260 (360–150 cal yr BP. Blechnum and Poaceae are identified by pollen analysis to be the dominant plants of the swamp surface over the past 4000 years. The ratio of these two plant taxa in the pollen record correlates well with identified wet and dry shifts. It is suggested that a ratio ≤1 possibly indicates dry conditions, a ratio of >1–3 indicates wet or dry conditions, and a ratio >3 implies wet conditions. Large macrocharcoal peaks are recorded during the initiation phase of the peat sequence at approximately 4090 cal. yr BP, and at 3700–3620 cal. yr BP, both of these time periods being coincident with dry phases. Isolated minor macrocharcoal peaks at ca. 2860, 2820, 2620, 2560, 2130, 1930, 1740 and 200 cal. yr BP are found to coincide with periods of average effective precipitation (based on the humification

  9. A regional chemical transport modeling to identify the influences of biomass burning during 2006 BASE-ASIA

    Science.gov (United States)

    Fu, J. S.; Hsu, N. C.; Gao, Y.; Huang, K.; Li, C.; Lin, N.-H.; Tsay, S.-C.

    2011-01-01

    To evaluate the impact of biomass burning from Southeast Asia to East Asia, this study conducted numerical simulations during NASA's 2006 Biomass-burning Aerosols in South-East Asia: Smoke Impact Assessment (BASE-ASIA). Two typical episode periods (27-28 March and 13-14 April) were examined. Two emission inventories, FLAMBE and GFED, were used in the simulations. The influences during two episodes in the source region (Southeast Asia) contributed to CO, O3 and PM2.5 concentrations as high as 400 ppbv, 20 ppbv and 80 μg/m3, respectively. The perturbations with and without biomass burning of the above three species were in the range of 10 to 60%, 10 to 20% and 30 to 70%, respectively. The impact due to long-range transport could spread over the southeastern parts of East Asia and could reach about 160 to 360 ppbv, 8 to 18 ppbv and 8 to 64 μg/m3 on CO, O3 and PM2.5, respectively; the percentage impact could reach 20 to 50% on CO, 10 to 30% on O3, and as high as 70% on PM2.5. An impact pattern can be found in April, while the impact becomes slightly broader and goes up to Yangtze River Delta. Two cross-sections at 15° N and 20° N were used to compare the vertical flux of biomass burning. In the source region (Southeast Asia), CO, O3 and PM2.5 concentrations had a strong upward tendency from surface to high altitudes. The eastward transport becomes strong from 2 to 8 km in the free troposphere. The subsidence contributed 60 to 70%, 20 to 50%, and 80% on CO, O3 and PM2.5, respectively to surface in the downwind area. The study reveals the significant impact of Southeastern Asia biomass burning on the air quality in both local and downwind areas, particularly during biomass burning episodes. This modeling study might provide constraints of lower limit. An additional study is underway for an active biomass burning year to obtain an upper limit and climate effects.

  10. Regional cerebellar volume and cognitive function from adolescence to late middle age.

    Science.gov (United States)

    Bernard, Jessica A; Leopold, Daniel R; Calhoun, Vince D; Mittal, Vijay A

    2015-03-01

    Cerebellar morphology and function have been implicated in a variety of developmental disorders, and in healthy aging. Although recent work has sought to characterize the relationships between volume and age in this structure during adolescence, young, and older adulthood, there have been no investigations of regional cerebellar volume from adolescence through late middle age. Middle age in particular has been largely understudied, and investigating this period of the lifespan may be especially important for our understanding of senescence. Understanding regional patterns of cerebellar volume with respect to age during this portion of the lifespan may provide important insight into healthy aging and cognitive function as well as pathology from adolescence into later life. We investigated regional cerebellar volume using a highly novel lobular segmentation approach in conjunction with a battery of cognitive tasks in a cross-sectional sample of 123 individuals from 12 to 65 years old. Our results indicated that regional cerebellar volumes show different patterns with respect to age. In particular, the more posterior aspect of the neocerebellum follows a quadratic "inverse-U" pattern while the vermis and anterior cerebellum follow logarithmic patterns. In addition, we quantified the relationships between age and a variety of cognitive assessments and found relationships between regional cerebellar volumes and performance. Finally, exploratory analyses of sex differences in the relationships between regional cerebellar volume, age, and cognition were investigated. Taken together, these results provide key insights into the development and aging of the human cerebellum, and its role in cognitive function across the lifespan. © 2014 Wiley Periodicals, Inc.

  11. Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.

    Directory of Open Access Journals (Sweden)

    Dana B Hancock

    Full Text Available Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1, and its ratio to forced vital capacity (FEV(1/FVC. Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA of single nucleotide polymorphism (SNP and SNP-by-smoking (ever-smoking or pack-years associations on FEV(1 and FEV(1/FVC across 19 studies (total N = 50,047. We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = 5.00×10(-11, HLA-DQB1 and HLA-DQA2 (smallest P(JMA = 4.35×10(-9, and KCNJ2 and SOX9 (smallest P(JMA = 1.28×10(-8 were associated with FEV(1/FVC or FEV(1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.

  12. Identifying functional network changing patterns in individuals at clinical high-risk for psychosis and patients with early illness schizophrenia: A group ICA study

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    Yuhui Du

    2018-01-01

    Full Text Available Although individuals at clinical high risk (CHR for psychosis exhibit a psychosis-risk syndrome involving attenuated forms of the positive symptoms typical of schizophrenia (SZ, it remains unclear whether their resting-state brain intrinsic functional networks (INs show attenuated or qualitatively distinct patterns of functional dysconnectivity relative to SZ patients. Based on resting-state functional magnetic imaging data from 70 healthy controls (HCs, 53 CHR individuals (among which 41 subjects were antipsychotic medication-naive, and 58 early illness SZ (ESZ patients (among which 53 patients took antipsychotic medication within five years of illness onset, we estimated subject-specific INs using a novel group information guided independent component analysis (GIG-ICA and investigated group differences in INs. We found that when compared to HCs, both CHR and ESZ groups showed significant differences, primarily in default mode, salience, auditory-related, visuospatial, sensory-motor, and parietal INs. Our findings suggest that widespread INs were diversely impacted. More than 25% of voxels in the identified significant discriminative regions (obtained using all 19 possible changing patterns excepting the no-difference pattern from six of the 15 interrogated INs exhibited monotonically decreasing Z-scores (in INs from the HC to CHR to ESZ, and the related regions included the left lingual gyrus of two vision-related networks, the right postcentral cortex of the visuospatial network, the left thalamus region of the salience network, the left calcarine region of the fronto-occipital network and fronto-parieto-occipital network. Compared to HCs and CHR individuals, ESZ patients showed both increasing and decreasing connectivity, mainly hypo-connectivity involving 15% of the altered voxels from four INs. The left supplementary motor area from the sensory-motor network and the right inferior occipital gyrus in the vision-related network showed a

  13. Quantitative trait loci (QTL study identifies novel genomic regions associated to Chiari-like malformation in Griffon Bruxellois dogs.

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    Philippe Lemay

    Full Text Available Chiari-like malformation (CM is a developmental abnormality of the craniocervical junction that is common in the Griffon Bruxellois (GB breed with an estimated prevalence of 65%. This disease is characterized by overcrowding of the neural parenchyma at the craniocervical junction and disturbance of cerebrospinal fluid (CSF flow. The most common clinical sign is pain either as a direct consequence of CM or neuropathic pain as a consequence of secondary syringomyelia. The etiology of CM remains unknown but genetic factors play an important role. To investigate the genetic complexity of the disease, a quantitative trait locus (QTL approach was adopted. A total of 14 quantitative skull and atlas measurements were taken and were tested for association to CM. Six traits were found to be associated to CM and were subjected to a whole-genome association study using the Illumina canine high density bead chip in 74 GB dogs (50 affected and 24 controls. Linear and mixed regression analyses identified associated single nucleotide polymorphisms (SNPs on 5 Canis Familiaris Autosomes (CFAs: CFA2, CFA9, CFA12, CFA14 and CFA24. A reconstructed haplotype of 0.53 Mb on CFA2 strongly associated to the height of the cranial fossa (diameter F and an haplotype of 2.5 Mb on CFA14 associated to both the height of the rostral part of the caudal cranial fossa (AE and the height of the brain (FG were significantly associated to CM after 10 000 permutations strengthening their candidacy for this disease (P = 0.0421, P = 0.0094 respectively. The CFA2 QTL harbours the Sall-1 gene which is an excellent candidate since its orthologue in humans is mutated in Townes-Brocks syndrome which has previously been associated to Chiari malformation I. Our study demonstrates the implication of multiple traits in the etiology of CM and has successfully identified two new QTL associated to CM and a potential candidate gene.

  14. Structural characterization of POM6 Fab and mouse prion protein complex identifies key regions for prions conformational conversion.

    Science.gov (United States)

    Baral, Pravas Kumar; Swayampakula, Mridula; Aguzzi, Adriano; James, Michael N G

    2018-05-01

    Conversion of the cellular prion protein PrP C into its pathogenic isoform PrP S c is the hallmark of prion diseases, fatal neurodegenerative diseases affecting many mammalian species including humans. Anti-prion monoclonal antibodies can arrest the progression of prion diseases by stabilizing the cellular form of the prion protein. Here, we present the crystal structure of the POM6 Fab fragment, in complex with the mouse prion protein (moPrP). The prion epitope of POM6 is in close proximity to the epitope recognized by the purportedly toxic antibody fragment, POM1 Fab also complexed with moPrP. The POM6 Fab recognizes a larger binding interface indicating a likely stronger binding compared to POM1. POM6 and POM1 exhibit distinct biological responses. Structural comparisons of the bound mouse prion proteins from the POM6 Fab:moPrP and POM1 Fab:moPrP complexes reveal several key regions of the prion protein that might be involved in initiating mis-folding events. The structural data of moPrP:POM6 Fab complex are available in the PDB under the accession number www.rcsb.org/pdb/search/structidSearch.do?structureId=6AQ7. © 2018 Federation of European Biochemical Societies.

  15. The REgolith X-Ray Imaging Spectrometer (REXIS) for OSIRIS-REx: identifying regional elemental enrichment on asteroids

    Science.gov (United States)

    Allen, Branden; Grindlay, Jonathan; Hong, Jaesub; Binzel, Richard P.; Masterson, Rebecca; Inamdar, Niraj K.; Chodas, Mark; Smith, Matthew W.; Bautz, Marshall W.; Kissel, Steven E.; Villasenor, Joel; Oprescu, Miruna; Induni, Nicholas

    2013-09-01

    The OSIRIS-REx Mission was selected under the NASA New Frontiers program and is scheduled for launch in September of 2016 for a rendezvous with, and collection of a sample from the surface of asteroid Bennu in 2019. 101955 Bennu (previously 1999 RQ36) is an Apollo (near-Earth) asteroid originally discovered by the LINEAR project in 1999 which has since been classified as a potentially hazardous near-Earth object. The REgolith X-Ray Imaging Spectrometer (REXIS) was proposed jointly by MIT and Harvard and was subsequently accepted as a student led instrument for the determination of the elemental composition of the asteroid's surface as well as the surface distribution of select elements through solar induced X-ray fluorescence. REXIS consists of a detector plane that contains 4 X-ray CCDs integrated into a wide field coded aperture telescope with a focal length of 20 em for the detection of regions with enhanced abundance in key elements at 50 m scales. Elemental surface distributions of approximately 50-200 m scales can be detected using the instrument as a simple collimator. An overview of the observation strategy of the REXIS instrument and expected performance are presented here.

  16. NMR imaging of the head-neck region. Topography of function - clinical findings - imaging and spectroscopy

    International Nuclear Information System (INIS)

    Vogl, T.J.

    1991-01-01

    The book on nmr imaging in the head-neck region offers, on a total of 221 pages, 344 detailed representations with 141 figures and 44 tables. It provides information as to the relevant topography of function, presents clinical findings, explains imaging characteristics and also takes account of spectroscopic procedures. The multifarious methods of investigation are described and discussed in connection with the differential diagnoses. A score of suitable diagnostic measures is assigned to each region of examination. The method's value is assessed against that of other imaging techniques. (orig.) [de

  17. Electron energy distribution function in a cathode fall region of DC-glow discharge

    International Nuclear Information System (INIS)

    Elakshar, F.F.; Garamoon, A.A.; Hassouba, M.A.

    1997-01-01

    Recently a substantial effort has been devoted towards the development of a quantitative microscopic measurements in the cathode fall region of the DC-glow discharge magnetron sputtering unit. The electron energy distribution function (EEDF) has been measured using a single Langmuir probe at the edge of the cathode fall. Two groups of electrons are observed in helium and argon gas discharges. The two groups have no chance to be thermalized since they leave the cathode fall region fast. The electron temperature measurements have been compared with spectroscopic determination. Plasma density has been computed and compared with probe measurements. Sources of the two groups of electrons are also discussed. (author)

  18. Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function.

    Science.gov (United States)

    Chasman, Daniel I; Fuchsberger, Christian; Pattaro, Cristian; Teumer, Alexander; Böger, Carsten A; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; O'Seaghdha, Conall M; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D; Gierman, Hinco J; Feitosa, Mary F; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Lambert, Jean-Charles; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Coassin, Stefan; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; de Andrade, Mariza; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Meisinger, Christa; Gieger, Christian; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S; van Duijn, Cornelia M; Borecki, Ingrid B; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Parsa, Afshin; Bochud, Murielle; Heid, Iris M; Kao, W H Linda; Fox, Caroline S; Köttgen, Anna

    2012-12-15

    In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10(-9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10(-4)-2.2 × 10(-7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.

  19. Identifying Potential Conservation Corridors Along the Mongolia-Russia Border Using Resource Selection Functions: A Case Study on Argali Sheep

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    Buyanaa Chimeddorj

    2013-12-01

    Full Text Available The disruption of animal movements is known to affect wildlife populations, particularly large bodied, free-ranging mammals that require large geographic ranges to survive. Corridors commonly connect fragmented wildlife populations and their habitats, yet identifying corridors rarely uses data on habitat selection and movements of target species. New technologies and analytical tools make it possible to better integrate landscape patterns with spatial behavioral data. We show how resource selection functions can describe habitat suitability using continuous and multivariate metrics to determine potential wildlife movement corridors. During 2005–2010, we studied movements of argali sheep ( Ovis ammon near the Mongolia-Russia border using radio-telemetry and modeled their spatial distribution in relation to landscape features to create a spatially explicit habitat suitability surface to identify potential transboundary conservation corridors. Argali sheep habitat selection in western Mongolia positively correlated with elevation, ruggedness index, and distance to border. In other words, argali were tended use areas with higher elevation, rugged topography, and distances farther from the international border. We suggest that these spatial modeling approaches offer ways to design and identify wildlife corridors more objectively and holistically, and can be applied to many other target species.

  20. Large-scale functional RNAi screen in C. elegans identifies genes that regulate the dysfunction of mutant polyglutamine neurons.

    Science.gov (United States)

    Lejeune, François-Xavier; Mesrob, Lilia; Parmentier, Frédéric; Bicep, Cedric; Vazquez-Manrique, Rafael P; Parker, J Alex; Vert, Jean-Philippe; Tourette, Cendrine; Neri, Christian

    2012-03-13

    A central goal in Huntington's disease (HD) research is to identify and prioritize candidate targets for neuroprotective intervention, which requires genome-scale information on the modifiers of early-stage neuron injury in HD. Here, we performed a large-scale RNA interference screen in C. elegans strains that express N-terminal huntingtin (htt) in touch receptor neurons. These neurons control the response to light touch. Their function is strongly impaired by expanded polyglutamines (128Q) as shown by the nearly complete loss of touch response in adult animals, providing an in vivo model in which to manipulate the early phases of expanded-polyQ neurotoxicity. In total, 6034 genes were examined, revealing 662 gene inactivations that either reduce or aggravate defective touch response in 128Q animals. Several genes were previously implicated in HD or neurodegenerative disease, suggesting that this screen has effectively identified candidate targets for HD. Network-based analysis emphasized a subset of high-confidence modifier genes in pathways of interest in HD including metabolic, neurodevelopmental and pro-survival pathways. Finally, 49 modifiers of 128Q-neuron dysfunction that are dysregulated in the striatum of either R/2 or CHL2 HD mice, or both, were identified. Collectively, these results highlight the relevance to HD pathogenesis, providing novel information on the potential therapeutic targets for neuroprotection in HD. © 2012 Lejeune et al; licensee BioMed Central Ltd.

  1. Identifying HIV associated neurocognitive disorder using large-scale Granger causality analysis on resting-state functional MRI

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    DSouza, Adora M.; Abidin, Anas Z.; Leistritz, Lutz; Wismüller, Axel

    2017-02-01

    We investigate the applicability of large-scale Granger Causality (lsGC) for extracting a measure of multivariate information flow between pairs of regional brain activities from resting-state functional MRI (fMRI) and test the effectiveness of these measures for predicting a disease state. Such pairwise multivariate measures of interaction provide high-dimensional representations of connectivity profiles for each subject and are used in a machine learning task to distinguish between healthy controls and individuals presenting with symptoms of HIV Associated Neurocognitive Disorder (HAND). Cognitive impairment in several domains can occur as a result of HIV infection of the central nervous system. The current paradigm for assessing such impairment is through neuropsychological testing. With fMRI data analysis, we aim at non-invasively capturing differences in brain connectivity patterns between healthy subjects and subjects presenting with symptoms of HAND. To classify the extracted interaction patterns among brain regions, we use a prototype-based learning algorithm called Generalized Matrix Learning Vector Quantization (GMLVQ). Our approach to characterize connectivity using lsGC followed by GMLVQ for subsequent classification yields good prediction results with an accuracy of 87% and an area under the ROC curve (AUC) of up to 0.90. We obtain a statistically significant improvement (p<0.01) over a conventional Granger causality approach (accuracy = 0.76, AUC = 0.74). High accuracy and AUC values using our multivariate method to connectivity analysis suggests that our approach is able to better capture changes in interaction patterns between different brain regions when compared to conventional Granger causality analysis known from the literature.

  2. Functional Investigations of HNF1A Identify Rare Variants as Risk Factors for Type 2 Diabetes in the General Population

    Science.gov (United States)

    Najmi, Laeya Abdoli; Aukrust, Ingvild; Flannick, Jason; Molnes, Janne; Burtt, Noel; Molven, Anders; Groop, Leif; Altshuler, David; Johansson, Stefan; Njølstad, Pål Rasmus

    2017-01-01

    Variants in HNF1A encoding hepatocyte nuclear factor 1α (HNF-1A) are associated with maturity-onset diabetes of the young form 3 (MODY 3) and type 2 diabetes. We investigated whether functional classification of HNF1A rare coding variants can inform models of diabetes risk prediction in the general population by analyzing the effect of 27 HNF1A variants identified in well-phenotyped populations (n = 4,115). Bioinformatics tools classified 11 variants as likely pathogenic and showed no association with diabetes risk (combined minor allele frequency [MAF] 0.22%; odds ratio [OR] 2.02; 95% CI 0.73–5.60; P = 0.18). However, a different set of 11 variants that reduced HNF-1A transcriptional activity to diabetes in the general population (combined MAF 0.22%; OR 5.04; 95% CI 1.99–12.80; P = 0.0007). Our functional investigations indicate that 0.44% of the population carry HNF1A variants that result in a substantially increased risk for developing diabetes. These results suggest that functional characterization of variants within MODY genes may overcome the limitations of bioinformatics tools for the purposes of presymptomatic diabetes risk prediction in the general population. PMID:27899486

  3. Comparative and functional genomics of Legionella identified eukaryotic like proteins as key players in host-pathogen interactions

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    Laura eGomez-Valero

    2011-10-01

    Full Text Available Although best known for its ability to cause severe pneumonia in people whose immune defenses are weakened, Legionella pneumophila and Legionella longbeachae are two species of a large genus of bacteria that are ubiquitous in nature, where they parasitize protozoa. Adaptation to the host environment and exploitation of host cell functions are critical for the success of these intracellular pathogens. The establishment and publication of the complete genome sequences of L. pneumophila and L. longbeachae isolates paved the way for major breakthroughs in understanding the biology of these organisms. In this review we present the knowledge gained from the analyses and comparison of the complete genome sequences of different L. pneumophila and L. longbeachae strains. Emphasis is given on putative virulence and Legionella life cycle related functions, such as the identification of an extended array of eukaryotic-like proteins, many of which have been shown to modulate host cell functions to the pathogen's advantage. Surprisingly, many of the eukaryotic domain proteins identified in L. pneumophila as well as many substrates of the Dot/Icm type IV secretion system essential for intracellular replication are different between these two species, although they cause the same disease. Finally, evolutionary aspects regarding the eukaryotic like proteins in Legionella are discussed.

  4. Elements in the transcriptional regulatory region flanking herpes simplex virus type 1 oriS stimulate origin function.

    Science.gov (United States)

    Wong, S W; Schaffer, P A

    1991-05-01

    Like other DNA-containing viruses, the three origins of herpes simplex virus type 1 (HSV-1) DNA replication are flanked by sequences containing transcriptional regulatory elements. In a transient plasmid replication assay, deletion of sequences comprising the transcriptional regulatory elements of ICP4 and ICP22/47, which flank oriS, resulted in a greater than 80-fold decrease in origin function compared with a plasmid, pOS-822, which retains these sequences. In an effort to identify specific cis-acting elements responsible for this effect, we conducted systematic deletion analysis of the flanking region with plasmid pOS-822 and tested the resulting mutant plasmids for origin function. Stimulation by cis-acting elements was shown to be both distance and orientation dependent, as changes in either parameter resulted in a decrease in oriS function. Additional evidence for the stimulatory effect of flanking sequences on origin function was demonstrated by replacement of these sequences with the cytomegalovirus immediate-early promoter, resulting in nearly wild-type levels of oriS function. In competition experiments, cotransfection of cells with the test plasmid, pOS-822, and increasing molar concentrations of a competitor plasmid which contained the ICP4 and ICP22/47 transcriptional regulatory regions but lacked core origin sequences resulted in a significant reduction in the replication efficiency of pOS-822, demonstrating that factors which bind specifically to the oriS-flanking sequences are likely involved as auxiliary proteins in oriS function. Together, these studies demonstrate that trans-acting factors and the sites to which they bind play a critical role in the efficiency of HSV-1 DNA replication from oriS in transient-replication assays.

  5. Immunochip analysis identifies novel susceptibility loci in the human leukocyte antigen region for acquired thrombotic thrombocytopenic purpura.

    Science.gov (United States)

    Mancini, I; Ricaño-Ponce, I; Pappalardo, E; Cairo, A; Gorski, M M; Casoli, G; Ferrari, B; Alberti, M; Mikovic, D; Noris, M; Wijmenga, C; Peyvandi, F

    2016-12-01

    Essentials Genetic predisposition to acquired thrombotic thrombocytopenic purpura (aTTP) is mainly unknown. Genetic risk factors for aTTP were studied by Immunochip analysis and replication study. Human leukocyte antigen (HLA) variant rs6903608 conferred a 2.5-fold higher risk of developing aTTP. rs6903608 and HLA-DQB1*05:03 may explain most of the HLA association signal in aTTP. Click to hear Dr Cataland's presentation on acquired thrombotic thrombocytopenic purpura SUMMARY: Background Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy associated with the development of autoantibodies against the von Willebrand factor-cleaving protease ADAMTS-13. Similarly to what has been found for other autoimmune disorders, there is evidence of a genetic contribution, including the association of the human leukocyte antigen (HLA) class II complex with disease risk. Objective To identify novel genetic risk factors in acquired TTP. Patients/Methods We undertook a case-control genetic association study in 190 European-origin TTP patients and 1255 Italian healthy controls by using the Illumina Immunochip. Replication analysis in 88 Italian cases and 456 controls was performed with single-nucleotide polymorphism (SNP) TaqMan assays. Results and conclusion We identified one common variant (rs6903608) located within the HLA class II locus that was independently associated with acquired TTP at genome-wide significance and conferred a 2.6-fold increased risk of developing a TTP episode (95% confidence interval [CI] 2.02-3.27, P = 1.64 × 10 -14 ). We also found five non-HLA variants mapping to chromosomes 2, 6, 8 and X that were suggestively associated with the disease: rs9490550, rs115265285, rs5927472, rs7823314, and rs1334768 (nominal P-values ranging from 1.59 × 10 -5 to 7.60 × 10 -5 ). Replication analysis confirmed the association of HLA variant rs6903608 with acquired TTP (pooled P = 3.95 × 10 -19 ). Imputation of classic

  6. High-Resolution Biogeochemical Simulation Identifies Practical Opportunities for Bioenergy Landscape Intensification Across Diverse US Agricultural Regions

    Science.gov (United States)

    Field, J.; Adler, P. R.; Evans, S.; Paustian, K.; Marx, E.; Easter, M.

    2015-12-01

    The sustainability of biofuel expansion is strongly dependent on the environmental footprint of feedstock production, including both direct impacts within feedstock-producing areas and potential leakage effects due to disruption of existing food, feed, or fiber production. Assessing and minimizing these impacts requires novel methods compared to traditional supply chain lifecycle assessment. When properly validated and applied at appropriate spatial resolutions, biogeochemical process models are useful for simulating how the productivity and soil greenhouse gas fluxes of cultivating both conventional crops and advanced feedstock crops respond across gradients of land quality and management intensity. In this work we use the DayCent model to assess the biogeochemical impacts of agricultural residue collection, establishment of perennial grasses on marginal cropland or conservation easements, and intensification of existing cropping at high spatial resolution across several real-world case study landscapes in diverse US agricultural regions. We integrate the resulting estimates of productivity, soil carbon changes, and nitrous oxide emissions with crop production budgets and lifecycle inventories, and perform a basic optimization to generate landscape cost/GHG frontiers and determine the most practical opportunities for low-impact feedstock provisioning. The optimization is constrained to assess the minimum combined impacts of residue collection, land use change, and intensification of existing agriculture necessary for the landscape to supply a commercial-scale biorefinery while maintaining exiting food, feed, and fiber production levels. These techniques can be used to assess how different feedstock provisioning strategies perform on both economic and environmental criteria, and sensitivity of performance to environmental and land use factors. The included figure shows an example feedstock cost-GHG mitigation tradeoff frontier for a commercial-scale cellulosic

  7. Dual breath-hold magnetic resonance cine evaluation of global and regional cardiac function

    International Nuclear Information System (INIS)

    Wintersperger, Bernd J.; Dietrich, Olaf; Huber, Armin; Reiser, Maximilian F.; Schoenberg, Stefan O.; Sincleair, Spencer; Runge, Val M.

    2007-01-01

    The purpose of our study was to evaluate the accuracy of a multislice cine magnetic resonance imaging (MRI) technique with parallel imaging in regard to global and regional left ventricular function. Forty-two individuals underwent cine MRI on a 1.5-tesla scanner. Cine MRI used a steady-state free precession technique and was performed as a single-slice technique (nonTSENSE cine) and an accelerated multislice technique (TSENSE cine) with five slices per breath-hold. End diastolic volume (EDV), end systolic volume (ESV), and ejection fraction (EF) were evaluated for all data sets and in regard to regional wall motion and regional wall motion analysis, and quantitative regional wall thickness and systolic thickening were also assessed. EDV, ESV, and EF based on TSENSE cine showed excellent correlation to the nonTSENSE cine approach (all r 2 =0.99, P<0.001). While EDV evaluations showed a small underestimation for TSENSE cine, ESV and EF showed accurate results compared with nonTSENSE cine. Both readers showed good agreement (κ=0.72) in regional wall motion assessment comparing both techniques. Data acquisition for the multislice approach was significantly shorter (∝75%) that in single-slice cine. We conclude that accurate evaluation of regional wall motion and left ventricular EF is possible using accelerated multislice cine MR with high spatial and temporal resolution. (orig.)

  8. Calibrating and Validating a Simulation Model to Identify Drivers of Urban Land Cover Change in the Baltimore, MD Metropolitan Region

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    Claire Jantz

    2014-09-01

    Full Text Available We build upon much of the accumulated knowledge of the widely used SLEUTH urban land change model and offer advances. First, we use SLEUTH’s exclusion/attraction layer to identify and test different urban land cover change drivers; second, we leverage SLEUTH’s self-modification capability to incorporate a demographic model; and third, we develop a validation procedure to quantify the influence of land cover change drivers and assess uncertainty. We found that, contrary to our a priori expectations, new development is not attracted to areas serviced by existing or planned water and sewer infrastructure. However, information about where population and employment growth is likely to occur did improve model performance. These findings point to the dominant role of centrifugal forces in post-industrial cities like Baltimore, MD. We successfully developed a demographic model that allowed us to constrain the SLEUTH model forecasts and address uncertainty related to the dynamic relationship between changes in population and employment and urban land use. Finally, we emphasize the importance of model validation. In this work the validation procedure played a key role in rigorously assessing the impacts of different exclusion/attraction layers and in assessing uncertainty related to population and employment forecasts.

  9. Resting-state functional connectivity of ventral parietal regions associated with attention reorienting and episodic recollection

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    Sander M Daselaar

    2013-02-01

    Full Text Available In functional neuroimaging studies, ventral parietal cortex (VPC is recruited by very different cognitive tasks. Explaining the contributions VPC to these tasks has become a topic of intense study and lively debate. Perception studies frequently find VPC activations during tasks involving attention-reorienting, and memory studies frequently find them during tasks involving episodic recollection. According to the Attention to Memory (AtoM model, both phenomena can be explained by the same VPC function: bottom-up attention. Yet, a recent functional MRI (fMRI meta-analysis suggested that attention-reorienting activations are more frequent in anterior VPC, whereas recollection activations are more frequent in posterior VPC. Also, there is evidence that anterior and posterior VPC regions have different functional connectivity patterns. To investigate these issues, we conducted a resting-state functional connectivity analysis using as seeds the center-of-mass of attention-reorienting and recollection activations in the meta-analysis, which were located in the supramarginal gyrus (SMG, around the temporo-parietal junction—TPJ and in the angular gyrus (AG, respectively. The SMG seed showed stronger connectivity with ventrolateral prefrontal cortex (VLPFC and occipito-temporal cortex, whereas the AG seed showed stronger connectivity with the hippocampus and default network regions. To investigate whether these connectivity differences were graded or sharp, VLPFC and hippocampal connectivity was measured in VPC regions traversing through the SMG and AG seeds. The results showed a graded pattern: VLPFC connectivity gradually decreases from SMG to AG, whereas hippocampal connectivity gradually increases from SMG to AG. Importantly, both gradients showed an abrupt break when extended beyond VPC borders. This finding suggests that functional differences between SMG and AG are more subtle than previously thought. These connectivity differences can be

  10. Identifying diagnostically-relevant resting state brain functional connectivity in the ventral posterior complex via genetic data mining in autism spectrum disorder.

    Science.gov (United States)

    Baldwin, Philip R; Curtis, Kaylah N; Patriquin, Michelle A; Wolf, Varina; Viswanath, Humsini; Shaw, Chad; Sakai, Yasunari; Salas, Ramiro

    2016-05-01

    Exome sequencing and copy number variation analyses continue to provide novel insight to the biological bases of autism spectrum disorder (ASD). The growing speed at which massive genetic data are produced causes serious lags in analysis and interpretation of the data. Thus, there is a need to develop systematic genetic data mining processes that facilitate efficient analysis of large datasets. We report a new genetic data mining system, ProcessGeneLists and integrated a list of ASD-related genes with currently available resources in gene expression and functional connectivity of the human brain. Our data-mining program successfully identified three primary regions of interest (ROIs) in the mouse brain: inferior colliculus, ventral posterior complex of the thalamus (VPC), and parafascicular nucleus (PFn). To understand its pathogenic relevance in ASD, we examined the resting state functional connectivity (RSFC) of the homologous ROIs in human brain with other brain regions that were previously implicated in the neuro-psychiatric features of ASD. Among them, the RSFC of the VPC with the medial frontal gyrus (MFG) was significantly more anticorrelated, whereas the RSFC of the PN with the globus pallidus was significantly increased in children with ASD compared with healthy children. Moreover, greater values of RSFC between VPC and MFG were correlated with severity index and repetitive behaviors in children with ASD. No significant RSFC differences were detected in adults with ASD. Together, these data demonstrate the utility of our data-mining program through identifying the aberrant connectivity of thalamo-cortical circuits in children with ASD. Autism Res 2016, 9: 553-562. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  11. Nodule worm infection in humans and wild primates in Uganda: cryptic species in a newly identified region of human transmission.

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    Ria R Ghai

    Full Text Available Soil-transmitted helminths (STHs are a major health concern in tropical and sub-tropical countries. Oesophagostomum infection is considered endemic to West Africa but has also been identified in Uganda, East Africa, among primates (including humans. However, the taxonomy and ecology of Oesophagostomum in Uganda have not been studied, except for in chimpanzees (Pan troglodytes, which are infected by both O. bifurcum and O. stephanostomum.We studied Oesophagostomum in Uganda in a community of non-human primates that live in close proximity to humans. Prevalence estimates based on microscopy were lower than those based on polymerase chain reaction (PCR, indicating greater sensitivity of PCR. Prevalence varied among host species, with humans and red colobus (Procolobus rufomitratus infected at lowest prevalence (25% and 41% by PCR, respectively, and chimpanzees, olive baboons (Papio anubis, and l'hoest monkeys (Cercopithecus lhoesti infected at highest prevalence (100% by PCR in all three species. Phylogenetic regression showed that primates travelling further and in smaller groups are at greatest risk of infection. Molecular phylogenetic analyses revealed three cryptic clades of Oesophagostomum that were not distinguishable based on morphological characteristics of their eggs. Of these, the clade with the greatest host range had not previously been described genetically. This novel clade infects humans, as well as five other species of primates.Multiple cryptic forms of Oesophagostomum circulate in the people and primates of western Uganda, and parasite clades differ in host range and cross-species transmission potential. Our results expand knowledge about human Oesophagostomum infection beyond the West African countries of Togo and Ghana, where the parasite is a known public health concern. Oesophagostomum infection in humans may be common throughout Sub-Saharan Africa, and the transmission of this neglected STH among primates, including zoonotic

  12. Regional Differences of Proteins Expressing in Adipose Depots Isolated from Cows, Steers and Bulls as Identified by a Proteomic Approach

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    Jin Hyoung Cho

    2016-08-01

    Full Text Available Adipose tissue in the loin muscle area of beef cattle as a marbling factor is directly associated with beef quality. To elucidate whether properties of proteins involved in depot specific adipose tissue were sex-dependent, we analyzed protein expression of intramuscular adipose tissue (IMAT and omental adipose tissue (OMAT from Hanwoo cows, steers, and bulls of Korean native beef cattle by liquid chromatography-tandem mass spectrometry (LC-MS/MS–based proteomic analysis, quantitative polymerase chain reaction (PCR and western blot analysis. Two different adipose depots (i.e. intramuscular and omental were collected from cows (n = 7, steers (n = 7, or bulls (n = 7. LC-MS/MS revealed a total of 55 and 35 proteins in IMAT and OMAT, respectively. Of the 55 proteins identified, 44, 40, and 42 proteins were confirmed to be differentially expressed in IMAT of cows, steers, and bulls, respectively. In OMAT of cows, steers, and bulls, 33, 33, and 22 were confirmed to be differentially expressed, respectively. Tropomyosin (TPM 1, TPM 2, and TPM3 were subjected to verification by quantitative PCR and western blot analysis in IMAT and OMAT of Hanwoo cows, steers, and bulls as key factors closely associated with muscle development. Both mRNA levels and protein levels of TPM1, TPM2, and TPM3 in IMAT were lower in bulls compared to in cows or steers suggesting that they were positively correlated with marbling score and quality grade. Our results may aid the regulation of marbling development and improvement of meat quality grades in beef cattle.

  13. Characterization of the sterol 14α-demethylases of Fusarium graminearum identifies a novel genus-specific CYP51 function.

    Science.gov (United States)

    Fan, Jieru; Urban, Martin; Parker, Josie E; Brewer, Helen C; Kelly, Steven L; Hammond-Kosack, Kim E; Fraaije, Bart A; Liu, Xili; Cools, Hans J

    2013-05-01

    CYP51 encodes the cytochrome P450 sterol 14α-demethylase, an enzyme essential for sterol biosynthesis and the target of azole fungicides. In Fusarium species, including pathogens of humans and plants, three CYP51 paralogues have been identified with one unique to the genus. Currently, the functions of these three genes and the rationale for their conservation within the genus Fusarium are unknown. Three Fusarium graminearum CYP51s (FgCYP51s) were heterologously expressed in Saccharomyces cerevisiae. Single and double FgCYP51 deletion mutants were generated and the functions of the FgCYP51s were characterized in vitro and in planta. FgCYP51A and FgCYP51B can complement yeast CYP51 function, whereas FgCYP51C cannot. FgCYP51A deletion increases the sensitivity of F. graminearum to the tested azoles. In ΔFgCYP51B and ΔFgCYP51BC mutants, ascospore formation is blocked, and eburicol and two additional 14-methylated sterols accumulate. FgCYP51C deletion reduces virulence on host wheat ears. FgCYP51B encodes the enzyme primarily responsible for sterol 14α-demethylation, and plays an essential role in ascospore formation. FgCYP51A encodes an additional sterol 14α-demethylase, induced on ergosterol depletion and responsible for the intrinsic variation in azole sensitivity. FgCYP51C does not encode a sterol 14α-demethylase, but is required for full virulence on host wheat ears. This is the first example of the functional diversification of a fungal CYP51. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  14. Editor's Highlight: High-Throughput Functional Genomics Identifies Modulators of TCE Metabolite Genotoxicity and Candidate Susceptibility Genes.

    Science.gov (United States)

    De La Rosa, Vanessa Y; Asfaha, Jonathan; Fasullo, Michael; Loguinov, Alex; Li, Peng; Moore, Lee E; Rothman, Nathaniel; Nakamura, Jun; Swenberg, James A; Scelo, Ghislaine; Zhang, Luoping; Smith, Martyn T; Vulpe, Chris D

    2017-11-01

    Trichloroethylene (TCE), an industrial chemical and environmental contaminant, is a human carcinogen. Reactive metabolites are implicated in renal carcinogenesis associated with TCE exposure, yet the toxicity mechanisms of these metabolites and their contribution to cancer and other adverse effects remain unclear. We employed an integrated functional genomics approach that combined functional profiling studies in yeast and avian DT40 cell models to provide new insights into the specific mechanisms contributing to toxicity associated with TCE metabolites. Genome-wide profiling studies in yeast identified the error-prone translesion synthesis (TLS) pathway as an import mechanism in response to TCE metabolites. The role of TLS DNA repair was further confirmed by functional profiling in DT40 avian cell lines, but also revealed that TLS and homologous recombination DNA repair likely play competing roles in cellular susceptibility to TCE metabolites in higher eukaryotes. These DNA repair pathways are highly conserved between yeast, DT40, and humans. We propose that in humans, mutagenic TLS is favored over homologous recombination repair in response to TCE metabolites. The results of these studies contribute to the body of evidence supporting a mutagenic mode of action for TCE-induced renal carcinogenesis mediated by reactive metabolites in humans. Our approach illustrates the potential for high-throughput in vitro functional profiling in yeast to elucidate toxicity pathways (molecular initiating events, key events) and candidate susceptibility genes for focused study. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Characterization of macular structure and function in two Swedish families with genetically identified autosomal dominant retinitis pigmentosa

    Science.gov (United States)

    Abdulridha-Aboud, Wissam; Kjellström, Ulrika; Andréasson, Sten

    2016-01-01

    Purpose To study the phenotype in two families with genetically identified autosomal dominant retinitis pigmentosa (adRP) focusing on macular structure and function. Methods Clinical data were collected at the Department of Ophthalmology, Lund University, Sweden, for affected and unaffected family members from two pedigrees with adRP. Examinations included optical coherence tomography (OCT), full-field electroretinography (ffERG), and multifocal electroretinography (mfERG). Molecular genetic screening was performed for known mutations associated with adRP. Results The mode of inheritance was autosomal dominant in both families. The members of the family with a mutation in the PRPF31 (p.IVS6+1G>T) gene had clinical features characteristic of RP, with severely reduced retinal rod and cone function. The degree of deterioration correlated well with increasing age. The mfERG showed only centrally preserved macular function that correlated well with retinal thinning on OCT. The family with a mutation in the RHO (p.R135W) gene had an extreme intrafamilial variability of the phenotype, with more severe disease in the younger generations. OCT showed pathology, but the degree of morphological changes was not correlated with age or with the mfERG results. The mother, with a de novo mutation in the RHO (p.R135W) gene, had a normal ffERG, and her retinal degeneration was detected merely with the reduced mfERG. Conclusions These two families demonstrate the extreme inter- and intrafamilial variability in the clinical phenotype of adRP. This is the first Swedish report of the clinical phenotype associated with a mutation in the PRPF31 (p.IVS6+1G>T) gene. Our results indicate that methods for assessment of the central retinal structure and function may improve the detection and characterization of the RP phenotype. PMID:27212874

  16. Genome-wide screens for in vivo Tinman binding sites identify cardiac enhancers with diverse functional architectures.

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    Hong Jin

    Full Text Available The NK homeodomain factor Tinman is a crucial regulator of early mesoderm patterning and, together with the GATA factor Pannier and the Dorsocross T-box factors, serves as one of the key cardiogenic factors during specification and differentiation of heart cells. Although the basic framework of regulatory interactions driving heart development has been worked out, only about a dozen genes involved in heart development have been designated as direct Tinman target genes to date, and detailed information about the functional architectures of their cardiac enhancers is lacking. We have used immunoprecipitation of chromatin (ChIP from embryos at two different stages of early cardiogenesis to obtain a global overview of the sequences bound by Tinman in vivo and their linked genes. Our data from the analysis of ~50 sequences with high Tinman occupancy show that the majority of such sequences act as enhancers in various mesodermal tissues in which Tinman is active. All of the dorsal mesodermal and cardiac enhancers, but not some of the others, require tinman function. The cardiac enhancers feature diverse arrangements of binding motifs for Tinman, Pannier, and Dorsocross. By employing these cardiac and non-cardiac enhancers in machine learning approaches, we identify a novel motif, termed CEE, as a classifier for cardiac enhancers. In vivo assays for the requirement of the binding motifs of Tinman, Pannier, and Dorsocross, as well as the CEE motifs in a set of cardiac enhancers, show that the Tinman sites are essential in all but one of the tested enhancers; although on occasion they can be functionally redundant with Dorsocross sites. The enhancers differ widely with respect to their requirement for Pannier, Dorsocross, and CEE sites, which we ascribe to their different position in the regulatory circuitry, their distinct temporal and spatial activities during cardiogenesis, and functional redundancies among different factor binding sites.

  17. Myocardial temperature variation: effect on regional function and coronary flow in dogs

    International Nuclear Information System (INIS)

    D'Ambra, M.N.; Magrassi, P.; Lowenstein, E.; Kyo, S.; Austen, W.G.; Buckley, M.J.; LaRaia, P.J.

    1987-01-01

    Incremental changes in the temperature (28-42.5 0 C) of the anterior left ventricular wall in a canine, working, beating right heart bypass preparation (constant preload, afterload, and heart rate) were produced to measure the effect of regional temperature on myocardial function and blood flow. Circumferential-axis segment lengths were measured with sonomicrometry in both the temperature-varied, left-anterior descending coronary artery (LAD)-supplied myocardium and the normothermic (38 0 C) circumflex-supplied myocardium. Fast thermistors (time constant 0 C), regional systolic shortening decreased 42.2 +/- 10% at 41 0 C and increased 23.3 +/- 6% at 31 0 C. There was no significant change in coronary blood flow or distribution at the three temperatures. Pressure-length areas varied inversely with myocardial temperature. These data demonstrate that there is a reversible inverse relationship between midwall T and ventricular function when heart rate, preload, and afterload are controlled

  18. Points of Economic and Innovative Growth: a Model for Organizing the Effective Functioning of the Region

    Directory of Open Access Journals (Sweden)

    D. D. Burkaltseva

    2017-01-01

    Full Text Available Abstract Purpose: the main goal of the article is to build a conceptual model for the organization of effective functioning of the points of economic and innovative growth of the region in modern conditions, taking into account regional and municipal limitations of internal and external nature, with the aim of ensuring economic security, effective interaction of subjects of the "business-power" system Taking into account the influence of institutional factors. Methods: the methodological basis of research in the article is the dialectical method of scientific cognition, the systemic and institutional approach to studying and building an organization for the effective functioning of the regional economy in order to ensure its economic security from internal and external threats. Results: the existing mechanism of interaction "business and power" is considered. The financial stability of economic entities of the Republic of Crimea is determined. The financial independence of the regional budget of the Republic of Crimea has been determined. The dynamics of financing of the Federal Target Program "Social and Economic Development of the Republic of Crimea and Sevastopol until 2020" has been revealed. The regional and municipal restrictions of internal and external nature, which constitute a threat to social and economic development, are indicated. Points of economic and innovative growth at the present stage and their advantages and stages of technical organization of their implementation have been determined. A conceptual model of building effective interaction between subjects of the "business-power" system is proposed taking into account the influence of institutional factors. The conceptual model of organization of effective functioning of points of economic and innovative growth of the region, as a territorial socio-economic system, under modern conditions is constructed. Conclusions and Relevance: we propose to define four

  19. Functional photoacoustic imaging to observe regional brain activation induced by cocaine hydrochloride

    Science.gov (United States)

    Jo, Janggun; Yang, Xinmai

    2011-09-01

    Photoacoustic microscopy (PAM) was used to detect small animal brain activation in response to drug abuse. Cocaine hydrochloride in saline solution was injected into the blood stream of Sprague Dawley rats through tail veins. The rat brain functional change in response to the injection of drug was then monitored by the PAM technique. Images in the coronal view of the rat brain at the locations of 1.2 and 3.4 mm posterior to bregma were obtained. The resulted photoacoustic (PA) images showed the regional changes in the blood volume. Additionally, the regional changes in blood oxygenation were also presented. The results demonstrated that PA imaging is capable of monitoring regional hemodynamic changes induced by drug abuse.

  20. Regional cerebral blood flow changes and neuropsychological functioning in early and late onset alcoholism

    International Nuclear Information System (INIS)

    Demir, B.; Ulug, B.; Ergun, E.; Erbas, B.

    2002-01-01

    Aim: Chronic alcoholism is strongly associated with morphologic and functional abnormalities in the brain. The age-of-onset of alcoholism symptoms might be of discriminating value and can be used to subdivide the population into more homogeneous groups. The aim of the study was to compare late and early onset alcoholism with regard to regional cerebral blood flow (rCBF) and neuropsychological functioning. Methods: Ten late onset (Type I) and thirteen early onset (Type II) male alcoholics were included in the study, the criterion being the age of onset for alcohol abuse. Six healthy, age-matched, male volunteers were included as a control group. rCBF changes were assessed using Tc-99m-HMPAO/SPECT after a detoxification period. Transaxial slices were assessed visually and semi quantitatively. Regional mean counts were divided to the mean counts of cerebellar and occipital regions to obtain semiquantitative ratios for superior frontal, middle frontal, inferior frontal, temporal and parietal lobes for the left and right hemispheres. The neuropsychological battery consisted of the Wisconsin Card Sorting Test, the Wechsler Memory Scale and the Word Fluency Test. Results: Type I and II groups had significantly asymmetric blood flow in the frontal region compared to control group (Left frontal percentage; Type I%46.8±2, Type II=48.3±2.3, Control=50.8±3, p=0.008). The semiquantitative ratios for the frontal subregions were lower for the patients compared to those of control group, however, statistically significant difference was observed only for the ratio of superior frontal region to occipital region in type I patients, for both left and right. The difference between the two subgroups was not statistically significant. Both groups of alcoholic patients also displayed impairment in frontal lobe functions and non-verbal memory. No significant difference was detected between the alcoholic subgroups on neuropsychological measures. There was no significant correlation

  1. Q2 dependence of the spin structure function in the resonance region

    International Nuclear Information System (INIS)

    Li, Z.; Li, Z.

    1994-01-01

    In this paper, we show what we can learn from the CEBAF experiments on spin-structure functions, and the transition from the Drell-Hearn-Gerasimov sum rule in the real photon limit to the spin-dependent sum rules in deep inelastic scattering, and how the asymmetry A 1 (x,Q 2 ) approaches the scaling limit in the resonance region. The spin structure function in the resonance region alone cannot determine the spin-dependent sum rule due to the kinematic restriction of the resonance region. The integral ∫ 0 1 {A 1 (x,Q 2 )F 2 (x,Q 2 )/2x[1+R(x,Q 2 )]}dx is estimated from Q 2 =0--2.5 GeV 2 . The result shows that there is a region where both contributions from the baryon resonances and the deep inelastic scattering are important; thus it provides important information on the high twist effects on the spin-dependent sum rule

  2. Tracking Regional Tissue Volume and Function Change in Lung Using Image Registration

    Directory of Open Access Journals (Sweden)

    Kunlin Cao

    2012-01-01

    Full Text Available We have previously demonstrated the 24-hour redistribution and reabsorption of bronchoalveolar lavage (BAL fluid delivered to the lung during a bronchoscopic procedure in normal volunteers. In this work we utilize image-matching procedures to correlate fluid redistribution and reabsorption to changes in regional lung function. Lung CT datasets from six human subjects were used in this study. Each subject was scanned at four time points before and after BAL procedure. Image registration was performed to align images at different time points and different inflation levels. The resulting dense displacement fields were utilized to track tissue volume changes and reveal deformation patterns of local parenchymal tissue quantitatively. The registration accuracy was assessed by measuring landmark matching errors, which were on the order of 1 mm. The results show that quantitative-assessed fluid volume agreed well with bronchoscopist-reported unretrieved BAL volume in the whole lungs (squared linear correlation coefficient was 0.81. The average difference of lung tissue volume at baseline and after 24 hours was around 2%, which indicates that BAL fluid in the lungs was almost absorbed after 24 hours. Regional lung-function changes correlated with the presence of BAL fluid, and regional function returned to baseline as the fluid was reabsorbed.

  3. NRC Information Notice No. 91-29, Supplement 1: Deficiencies identified during electrical distribution system functional inspections

    International Nuclear Information System (INIS)

    Rossi, C.E.

    1993-01-01

    During multidiscipline inspections such as safety system functional inspections (SSFIs) or safety system outage modification inspections (SSOMIs), the NRC identified a number of deficiencies related to the electrical distribution system (EDS). As a result of these deficiencies, the NRC developed the EDSFI to specifically evaluate the EDS. Since 1989, the NRC has performed over 50 EDSFIs, and found design weaknesses in the following generic areas: (1) undervoltage relay setpoints for degraded grid conditions; (2) interrupting capacity of fault protection devices; (3) improper coordination of fault protection devices; (4) analysis of emergency diesel generator (EDG) capacity to power safety-related loads during postulated accidents; and (5) EDG mechanical interfaces. Each of these issues are discussed

  4. Developing clinical practice guidelines: target audiences, identifying topics for guidelines, guideline group composition and functioning and conflicts of interest.

    Science.gov (United States)

    Eccles, Martin P; Grimshaw, Jeremy M; Shekelle, Paul; Schünemann, Holger J; Woolf, Steven

    2012-07-04

    Clinical practice guidelines are one of the foundations of efforts to improve health care. In 1999, we authored a paper about methods to develop guidelines. Since it was published, the methods of guideline development have progressed both in terms of methods and necessary procedures and the context for guideline development has changed with the emergence of guideline clearing houses and large scale guideline production organisations (such as the UK National Institute for Health and Clinical Excellence). It therefore seems timely to, in a series of three articles, update and extend our earlier paper. In this first paper we discuss: the target audience(s) for guidelines and their use of guidelines; identifying topics for guidelines; guideline group composition (including consumer involvement) and the processes by which guideline groups function and the important procedural issue of managing conflicts of interest in guideline development.

  5. Attempt to identify the functional areas of the cerebral cortex on CT slices parallel to the orbito-meatal line

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, Hirotaka; Okuda, Junichiro; Nishikawa, Takashi; Nishimura, Tsuyoshi (Osaka Univ. (Japan). Faculty of Medicine); Shiraishi, Junzo

    1982-06-01

    In order to identify the functional brain areas, such as Broca's area, on computed tomography slices parallel to the orbito-meatal line, the numbers of Brodmann's cortical mapping were shown on a diagram of representative brain sections parallel to the orbito-meatal line. Also, we described a method, using cerebral sulci as anatomical landmarks, for projecting lesions shown by CT scan onto the lateral brain diagram. The procedures were as follows. The distribution of lesions on CT slices was determined by the identification of major cerebral sulci and fissures, such as the Sylvian fissure, the central sulcus, and the superior frontal sulcus. Those lesions were then projected onto the lateral diagram by comparing each CT slice with the horizontal diagrams of brain sections. The method was demonstrated in three cases developing neuropsychological symptoms.

  6. Regulatory network analysis of Epstein-Barr virus identifies functional modules and hub genes involved in infectious mononucleosis.

    Science.gov (United States)

    Poorebrahim, Mansour; Salarian, Ali; Najafi, Saeideh; Abazari, Mohammad Foad; Aleagha, Maryam Nouri; Dadras, Mohammad Nasr; Jazayeri, Seyed Mohammad; Ataei, Atousa; Poortahmasebi, Vahdat

    2017-05-01

    Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis (IM) and establishes lifetime infection associated with a variety of cancers and autoimmune diseases. The aim of this study was to develop an integrative gene regulatory network (GRN) approach and overlying gene expression data to identify the representative subnetworks for IM and EBV latent infection (LI). After identifying differentially expressed genes (DEGs) in both IM and LI gene expression profiles, functional annotations were applied using gene ontology (GO) and BiNGO tools, and construction of GRNs, topological analysis and identification of modules were carried out using several plugins of Cytoscape. In parallel, a human-EBV GRN was generated using the Hu-Vir database for further analyses. Our analysis revealed that the majority of DEGs in both IM and LI were involved in cell-cycle and DNA repair processes. However, these genes showed a significant negative correlation in the IM and LI states. Furthermore, cyclin-dependent kinase 2 (CDK2) - a hub gene with the highest centrality score - appeared to be the key player in cell cycle regulation in IM disease. The most significant functional modules in the IM and LI states were involved in the regulation of the cell cycle and apoptosis, respectively. Human-EBV network analysis revealed several direct targets of EBV proteins during IM disease. Our study provides an important first report on the response to IM/LI EBV infection in humans. An important aspect of our data was the upregulation of genes associated with cell cycle progression and proliferation.

  7. Identifying the most efficient items from the Mini-Mental State Examination for cognitive function assessment in older Taiwanese patients.

    Science.gov (United States)

    Lou, Meei-Fang; Dai, Yu-Tzu; Huang, Guey-Shiun; Yu, Po-Jui

    2007-03-01

    The purpose of the study was to identify the most efficient items from the Mini-Mental State Examination for assessment of cognitive function. The Mini-Mental State Examination is the most frequently used cognitive screening instrument. However, the Mini-Mental State Examination has been criticized for insensitivity to mild cognitive dysfunction, limited memory assessment and variability in level of difficulty of the individual items. This study used secondary data analysis. Item response theory two-parameter model was used to analyse the data from the admission assessment of mental status by the Mini-Mental State Examination for 801 patients. By using item response analysis, 16 items were selected from the original 30-item Mini-Mental State Examination. The 16 items included mainly the measures of orientation, recall and attention and calculation. The internal consistency of the 16-item Mini-Mental State Examination was 0.84. The proposed new cut-off point for the 16-item Mini-Mental State Examination was 11. The correct classification rate was 0.94, the sensitivity was 100% and the specificity was 97.4%, when compared with the original 30-item Mini-Mental State Examination from the cut-off point of 24. This new cut-off point was determined for the purpose of over-identifying patients at risk so as to ensure early detection of and prevention from the onset of cognitive disturbance. Only a few items are needed to describe the subject's cognitive status. Using item response theory analysis, the study found that the Mini-Mental State Examination could be simplified. Deleting the items with less variation makes this assessment tool not only shorter, easier to administer and less strenuous for respondents, but also enables one to maintain validity as a cognitive function test for clinical setting.

  8. Genome-wide linkage, exome sequencing and functional analyses identify ABCB6 as the pathogenic gene of dyschromatosis universalis hereditaria.

    Directory of Open Access Journals (Sweden)

    Hong Liu

    Full Text Available As a genetic disorder of abnormal pigmentation, the molecular basis of dyschromatosis universalis hereditaria (DUH had remained unclear until recently when ABCB6 was reported as a causative gene of DUH.We performed genome-wide linkage scan using Illumina Human 660W-Quad BeadChip and exome sequencing analyses using Agilent SureSelect Human All Exon Kits in a multiplex Chinese DUH family to identify the pathogenic mutations and verified the candidate mutations using Sanger sequencing. Quantitative RT-PCR and Immunohistochemistry was performed to verify the expression of the pathogenic gene, Zebrafish was also used to confirm the functional role of ABCB6 in melanocytes and pigmentation.Genome-wide linkage (assuming autosomal dominant inheritance mode and exome sequencing analyses identified ABCB6 as the disease candidate gene by discovering a coding mutation (c.1358C>T; p.Ala453Val that co-segregates with the disease phenotype. Further mutation analysis of ABCB6 in four other DUH families and two sporadic cases by Sanger sequencing confirmed the mutation (c.1358C>T; p.Ala453Val and discovered a second, co-segregating coding mutation (c.964A>C; p.Ser322Lys in one of the four families. Both mutations were heterozygous in DUH patients and not present in the 1000 Genome Project and dbSNP database as well as 1,516 unrelated Chinese healthy controls. Expression analysis in human skin and mutagenesis interrogation in zebrafish confirmed the functional role of ABCB6 in melanocytes and pigmentation. Given the involvement of ABCB6 mutations in coloboma, we performed ophthalmological examination of the DUH carriers of ABCB6 mutations and found ocular abnormalities in them.Our study has advanced our understanding of DUH pathogenesis and revealed the shared pathological mechanism between pigmentary DUH and ocular coloboma.

  9. Using Long-Term Satellite Observations to Identify Sensitive Regimes and Active Regions of Aerosol Indirect Effects for Liquid Clouds Over Global Oceans

    Science.gov (United States)

    Zhao, Xuepeng; Liu, Yangang; Yu, Fangquan; Heidinger, Andrew K.

    2018-01-01

    Long-term (1981-2011) satellite climate data records of clouds and aerosols are used to investigate the aerosol-cloud interaction of marine water cloud from a climatology perspective. Our focus is on identifying the regimes and regions where the aerosol indirect effects (AIEs) are evident in long-term averages over the global oceans through analyzing the correlation features between aerosol loading and the key cloud variables including cloud droplet effective radius (CDER), cloud optical depth (COD), cloud water path (CWP), cloud top height (CTH), and cloud top temperature (CTT). An aerosol optical thickness (AOT) range of 0.13 change of long-term averaged CDER appears only in limited oceanic regions. The signature of aerosol invigoration of water clouds as revealed by the increase of cloud cover fraction (CCF) and CTH with increasing AOT at the middle/high latitudes of both hemispheres is identified for a pristine atmosphere (AOT polluted marine atmosphere (AOT > 0.3) in the tropical convergence zones. The regions where the second AIE is likely to manifest in the CCF change are limited to several oceanic areas with high CCF of the warm water clouds near the western coasts of continents. The second AIE signature as represented by the reduction of the precipitation efficiency with increasing AOT is more likely to be observed in the AOT regime of 0.08 < AOT < 0.4. The corresponding AIE active regions manifested themselves as the decline of the precipitation efficiency are mainly limited to the oceanic areas downwind of continental aerosols. The sensitive regime of the conventional AIE identified in this observational study is likely associated with the transitional regime from the aerosol-limited regime to the updraft-limited regime identified for aerosol-cloud interaction in cloud model simulations.

  10. Mobile NBM - Android medical mobile application designed to help in learning how to identify the different regions of interest in the brain's white matter.

    Science.gov (United States)

    Sánchez-Rola, Iskander; Zapirain, Begoña García

    2014-07-18

    One of the most critical tasks when conducting neurological studies is identifying the different regions of interest in the brain's white matter. Currently few programs or applications are available that serve as an interactive guide in this process. This is why a mobile application has been designed and developed in order to teach users how to identify the referred regions of the brain. It also enables users to share the results obtained and take an examination on the knowledge thus learnt. In order to provide direct user-user or user-developer contact, the project includes a website and a Twitter account. An application has been designed with a basic, minimalist look, which anyone can access easily in order to learn to identify a specific region in the brain's white matter. A survey has also been conducted on people who have used it, which has shown that the application is attractive both in the student (final mean satisfaction of 4.2/5) and in the professional (final mean satisfaction of 4.3/5) environment. The response obtained in the online part of the project reflects the high practical value and quality of the application, as shown by the fact that the website has seen a large number of visitors (over 1000 visitors) and the Twitter account has a high number of followers (over 280 followers). Mobile NBM is the first mobile application to be used as a guide in the process of identifying a region of interest in the brain's white matter. Although initially not many areas are available in the application, new ones can be added as required by users in their respective studies. Apart from the application itself, the online resources provided (website and Twitter account) significantly enhance users' experience.

  11. Jet reconstruction and measurement of identified fragmentation functions in Pb-Pb and pp collisions with the ALICE experiment

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Xianguo; Busch, Oliver [Physikalisches Institut, Heidelberg (Germany); Collaboration: ALICE-Collaboration

    2014-07-01

    Jets are defined in QCD as cascades of consecutive emission of partons from an initial hard scattering. The process of parton showering and subsequent hadronisation is broadly known as fragmentation. High energy nucleus-nucleus collisions allow us to probe parton fragmentation within a QCD medium and the properties of this medium via the modification of the jet spectrum and jet structure. Jet reconstruction in pp collisions provides an elementary baseline and allows to investigate perturbative and non-perturbative aspects of particle production. In addition to inclusive probes, identified particles in the final states provide an enhanced sensitivity to the flavor dependence of fragmentation and nuclear modifications. ALICE at the CERN LHC is a general-purpose heavy ion experiment designed to study the physics of strongly interacting matter and the Quark-Gluon-Plasma. It has an excellent tracking and particle identification performance over a wide momentum range. In this talk we present results on inclusive jet observable as well as the novel measurements of identified fragmentation functions in pp and Pb-Pb collisions. The results are confronted with theory predictions.

  12. Targeted next generation sequencing identifies functionally deleterious germline mutations in novel genes in early-onset/familial prostate cancer.

    Directory of Open Access Journals (Sweden)

    Paula Paulo

    2018-04-01

    Full Text Available Considering that mutations in known prostate cancer (PrCa predisposition genes, including those responsible for hereditary breast/ovarian cancer and Lynch syndromes, explain less than 5% of early-onset/familial PrCa, we have sequenced 94 genes associated with cancer predisposition using next generation sequencing (NGS in a series of 121 PrCa patients. We found monoallelic truncating/functionally deleterious mutations in seven genes, including ATM and CHEK2, which have previously been associated with PrCa predisposition, and five new candidate PrCa associated genes involved in cancer predisposing recessive disorders, namely RAD51C, FANCD2, FANCI, CEP57 and RECQL4. Furthermore, using in silico pathogenicity prediction of missense variants among 18 genes associated with breast/ovarian cancer and/or Lynch syndrome, followed by KASP genotyping in 710 healthy controls, we identified "likely pathogenic" missense variants in ATM, BRIP1, CHEK2 and TP53. In conclusion, this study has identified putative PrCa predisposing germline mutations in 14.9% of early-onset/familial PrCa patients. Further data will be necessary to confirm the genetic heterogeneity of inherited PrCa predisposition hinted in this study.

  13. Chemical screening identifies ROCK as a target for recovering mitochondrial function in Hutchinson-Gilford progeria syndrome.

    Science.gov (United States)

    Kang, Hyun Tae; Park, Joon Tae; Choi, Kobong; Choi, Hyo Jei Claudia; Jung, Chul Won; Kim, Gyu Ree; Lee, Young-Sam; Park, Sang Chul

    2017-06-01

    Hutchinson-Gilford progeria syndrome (HGPS) constitutes a genetic disease wherein an aging phenotype manifests in childhood. Recent studies indicate that reactive oxygen species (ROS) play important roles in HGPS phenotype progression. Thus, pharmacological reduction in ROS levels has been proposed as a potentially effective treatment for patient with this disorder. In this study, we performed high-throughput screening to find compounds that could reduce ROS levels in HGPS fibroblasts and identified rho-associated protein kinase (ROCK) inhibitor (Y-27632) as an effective agent. To elucidate the underlying mechanism of ROCK in regulating ROS levels, we performed a yeast two-hybrid screen and discovered that ROCK1 interacts with Rac1b. ROCK activation phosphorylated Rac1b at Ser71 and increased ROS levels by facilitating the interaction between Rac1b and cytochrome c. Conversely, ROCK inactivation with Y-27632 abolished their interaction, concomitant with ROS reduction. Additionally, ROCK activation resulted in mitochondrial dysfunction, whereas ROCK inactivation with Y-27632 induced the recovery of mitochondrial function. Furthermore, a reduction in the frequency of abnormal nuclear morphology and DNA double-strand breaks was observed along with decreased ROS levels. Thus, our study reveals a novel mechanism through which alleviation of the HGPS phenotype is mediated by the recovery of mitochondrial function upon ROCK inactivation. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  14. A quadratically regularized functional canonical correlation analysis for identifying the global structure of pleiotropy with NGS data.

    Science.gov (United States)

    Lin, Nan; Zhu, Yun; Fan, Ruzong; Xiong, Momiao

    2017-10-01

    Investigating the pleiotropic effects of genetic variants can increase statistical power, provide important information to achieve deep understanding of the complex genetic structures of disease, and offer powerful tools for designing effective treatments with fewer side effects. However, the current multiple phenotype association analysis paradigm lacks breadth (number of phenotypes and genetic variants jointly analyzed at the same time) and depth (hierarchical structure of phenotype and genotypes). A key issue for high dimensional pleiotropic analysis is to effectively extract informative internal representation and features from high dimensional genotype and phenotype data. To explore correlation information of genetic variants, effectively reduce data dimensions, and overcome critical barriers in advancing the development of novel statistical methods and computational algorithms for genetic pleiotropic analysis, we proposed a new statistic method referred to as a quadratically regularized functional CCA (QRFCCA) for association analysis which combines three approaches: (1) quadratically regularized matrix factorization, (2) functional data analysis and (3) canonical correlation analysis (CCA). Large-scale simulations show that the QRFCCA has a much higher power than that of the ten competing statistics while retaining the appropriate type 1 errors. To further evaluate performance, the QRFCCA and ten other statistics are applied to the whole genome sequencing dataset from the TwinsUK study. We identify a total of 79 genes with rare variants and 67 genes with common variants significantly associated with the 46 traits using QRFCCA. The results show that the QRFCCA substantially outperforms the ten other statistics.

  15. TDDFT calculations and photoacoustic spectroscopy experiments used to identify phenolic acid functional biomolecules in Brazilian tropical fruits in natura

    Science.gov (United States)

    Lourenço Neto, M.; Agra, K. L.; Suassuna Filho, J.; Jorge, F. E.

    2018-03-01

    Time-dependent density functional theory (TDDFT) calculations of electronic transitions have been widely used to determine molecular structures. The excitation wavelengths and oscillator strengths obtained with the hybrid exchange-correlation functional B3LYP in conjunction with the ADZP basis set are employed to simulate the UV-Vis spectra of eight phenolic acids. Experimental and theoretical UV-Vis spectra reported previously in the literature are compared with our results. The fast, sensitive and non-destructive technique of photoacoustic spectroscopy (PAS) is used to determine the UV-Vis spectra of four Brazilian tropical fresh fruits in natura. Then, the PAS along with the TDDFT results are for the first time used to investigate and identify the presence of phenolic acids in the fruits studied in this work. This theoretical method with this experimental technique show to be a powerful and cheap tool to detect the existence of phenolic acids in fruits, vegetables, cereals, and grains. Comparison with high performance liquid chromatography results, when available, is also carried out.

  16. Use of the Operon Structure of the C. elegans Genome as a Tool to Identify Functionally Related Proteins

    Directory of Open Access Journals (Sweden)

    Silvia Dossena

    2013-12-01

    Full Text Available One of the most pressing challenges in the post genomic era is the identification and characterization of protein-protein interactions (PPIs, as these are essential in understanding the cellular physiology of health and disease. Experimental techniques suitable for characterizing PPIs (X-ray crystallography or nuclear magnetic resonance spectroscopy, among others are usually laborious, time-consuming and often difficult to apply to membrane proteins, and therefore require accurate prediction of the candidate interacting partners. High-throughput experimental methods (yeast two-hybrid and affinity purification succumb to the same shortcomings, and can also lead to high rates of false positive and negative results. Therefore, reliable tools for predicting PPIs are needed. The use of the operon structure in the eukaryote Caenorhabditis elegans genome is a valuable, though underserved, tool for identifying physically or functionally interacting proteins. Based on the concept that genes organized in the same operon may encode physically or functionally related proteins, this algorithm is easy to be applied and, importantly, gives a limited number of candidate partners of a given protein, allowing for focused experimental verification. Moreover, this approach can be successfully used to predict PPIs in the human system, including those of membrane proteins.

  17. Molecular and functional analyses of a maize autoactive NB-LRR protein identify precise structural requirements for activity.

    Directory of Open Access Journals (Sweden)

    Guan-Feng Wang

    2015-02-01

    Full Text Available Plant disease resistance is often mediated by nucleotide binding-leucine rich repeat (NLR proteins which remain auto-inhibited until recognition of specific pathogen-derived molecules causes their activation, triggering a rapid, localized cell death called a hypersensitive response (HR. Three domains are recognized in one of the major classes of NLR proteins: a coiled-coil (CC, a nucleotide binding (NB-ARC and a leucine rich repeat (LRR domains. The maize NLR gene Rp1-D21 derives from an intergenic recombination event between two NLR genes, Rp1-D and Rp1-dp2 and confers an autoactive HR. We report systematic structural and functional analyses of Rp1 proteins in maize and N. benthamiana to characterize the molecular mechanism of NLR activation/auto-inhibition. We derive a model comprising the following three main features: Rp1 proteins appear to self-associate to become competent for activity. The CC domain is signaling-competent and is sufficient to induce HR. This can be suppressed by the NB-ARC domain through direct interaction. In autoactive proteins, the interaction of the LRR domain with the NB-ARC domain causes de-repression and thus disrupts the inhibition of HR. Further, we identify specific amino acids and combinations thereof that are important for the auto-inhibition/activity of Rp1 proteins. We also provide evidence for the function of MHD2, a previously uncharacterized, though widely conserved NLR motif. This work reports several novel insights into the precise structural requirement for NLR function and informs efforts towards utilizing these proteins for engineering disease resistance.

  18. Molecular and functional analyses of a maize autoactive NB-LRR protein identify precise structural requirements for activity.

    Science.gov (United States)

    Wang, Guan-Feng; Ji, Jiabing; El-Kasmi, Farid; Dangl, Jeffery L; Johal, Guri; Balint-Kurti, Peter J

    2015-02-01

    Plant disease resistance is often mediated by nucleotide binding-leucine rich repeat (NLR) proteins which remain auto-inhibited until recognition of specific pathogen-derived molecules causes their activation, triggering a rapid, localized cell death called a hypersensitive response (HR). Three domains are recognized in one of the major classes of NLR proteins: a coiled-coil (CC), a nucleotide binding (NB-ARC) and a leucine rich repeat (LRR) domains. The maize NLR gene Rp1-D21 derives from an intergenic recombination event between two NLR genes, Rp1-D and Rp1-dp2 and confers an autoactive HR. We report systematic structural and functional analyses of Rp1 proteins in maize and N. benthamiana to characterize the molecular mechanism of NLR activation/auto-inhibition. We derive a model comprising the following three main features: Rp1 proteins appear to self-associate to become competent for activity. The CC domain is signaling-competent and is sufficient to induce HR. This can be suppressed by the NB-ARC domain through direct interaction. In autoactive proteins, the interaction of the LRR domain with the NB-ARC domain causes de-repression and thus disrupts the inhibition of HR. Further, we identify specific amino acids and combinations thereof that are important for the auto-inhibition/activity of Rp1 proteins. We also provide evidence for the function of MHD2, a previously uncharacterized, though widely conserved NLR motif. This work reports several novel insights into the precise structural requirement for NLR function and informs efforts towards utilizing these proteins for engineering disease resistance.

  19. Identifying dynamic functional connectivity biomarkers using GIG-ICA: Application to schizophrenia, schizoaffective disorder, and psychotic bipolar disorder.

    Science.gov (United States)

    Du, Yuhui; Pearlson, Godfrey D; Lin, Dongdong; Sui, Jing; Chen, Jiayu; Salman, Mustafa; Tamminga, Carol A; Ivleva, Elena I; Sweeney, John A; Keshavan, Matcheri S; Clementz, Brett A; Bustillo, Juan; Calhoun, Vince D

    2017-05-01

    Functional magnetic resonance imaging (fMRI) studies have shown altered brain dynamic functional connectivity (DFC) in mental disorders. Here, we aim to explore DFC across a spectrum of symptomatically-related disorders including bipolar disorder with psychosis (BPP), schizoaffective disorder (SAD), and schizophrenia (SZ). We introduce a group information guided independent component analysis procedure to estimate both group-level and subject-specific connectivity states from DFC. Using resting-state fMRI data of 238 healthy controls (HCs), 140 BPP, 132 SAD, and 113 SZ patients, we identified measures differentiating groups from the whole-brain DFC and traditional static functional connectivity (SFC), separately. Results show that DFC provided more informative measures than SFC. Diagnosis-related connectivity states were evident using DFC analysis. For the dominant state consistent across groups, we found 22 instances of hypoconnectivity (with decreasing trends from HC to BPP to SAD to SZ) mainly involving post-central, frontal, and cerebellar cortices as well as 34 examples of hyperconnectivity (with increasing trends HC through SZ) primarily involving thalamus and temporal cortices. Hypoconnectivities/hyperconnectivities also showed negative/positive correlations, respectively, with clinical symptom scores. Specifically, hypoconnectivities linking postcentral and frontal gyri were significantly negatively correlated with the PANSS positive/negative scores. For frontal connectivities, BPP resembled HC while SAD and SZ were more similar. Three connectivities involving the left cerebellar crus differentiated SZ from other groups and one connection linking frontal and fusiform cortices showed a SAD-unique change. In summary, our method is promising for assessing DFC and may yield imaging biomarkers for quantifying the dimension of psychosis. Hum Brain Mapp 38:2683-2708, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. Identifying patterns of motor performance, executive functioning, and verbal ability in preschool children: A latent profile analysis.

    Science.gov (United States)

    Houwen, Suzanne; Kamphorst, Erica; van der Veer, Gerda; Cantell, Marja

    2018-04-30

    A relationship between motor performance and cognitive functioning is increasingly being recognized. Yet, little is known about the precise nature of the relationship between both domains, especially in early childhood. To identify distinct constellations of motor performance, executive functioning (EF), and verbal ability in preschool aged children; and to explore how individual and contextual variables are related to profile membership. The sample consisted of 119 3- to 4-year old children (62 boys; 52%). The home based assessments consisted of a standardized motor test (Movement Assessment Battery for Children - 2), five performance-based EF tasks measuring inhibition and working memory, and the Receptive Vocabulary subtest from the Wechsler Preschool and Primary Scale of Intelligence Third Edition. Parents filled out the Behavior Rating Inventory of Executive Function - Preschool version. Latent profile analysis (LPA) was used to delineate profiles of motor performance, EF, and verbal ability. Chi-square statistics and multinomial logistic regression analysis were used to examine whether profile membership was predicted by age, gender, risk of motor coordination difficulties, ADHD symptomatology, language problems, and socioeconomic status (SES). LPA yielded three profiles with qualitatively distinct response patterns of motor performance, EF, and verbal ability. Quantitatively, the profiles showed most pronounced differences with regard to parent ratings and performance-based tests of EF, as well as verbal ability. Risk of motor coordination difficulties and ADHD symptomatology were associated with profile membership, whereas age, gender, language problems, and SES were not. Our results indicate that there are distinct subpopulations of children who show differential relations with regard to motor performance, EF, and verbal ability. The fact that we found both quantitative as well as qualitative differences between the three patterns of profiles underscores

  1. QTL-seq approach identified genomic regions and diagnostic markers for rust and late leaf spot resistance in groundnut (Arachis hypogaea L.).

    Science.gov (United States)

    Pandey, Manish K; Khan, Aamir W; Singh, Vikas K; Vishwakarma, Manish K; Shasidhar, Yaduru; Kumar, Vinay; Garg, Vanika; Bhat, Ramesh S; Chitikineni, Annapurna; Janila, Pasupuleti; Guo, Baozhu; Varshney, Rajeev K

    2017-08-01

    Rust and late leaf spot (LLS) are the two major foliar fungal diseases in groundnut, and their co-occurrence leads to significant yield loss in addition to the deterioration of fodder quality. To identify candidate genomic regions controlling resistance to rust and LLS, whole-genome resequencing (WGRS)-based approach referred as 'QTL-seq' was deployed. A total of 231.67 Gb raw and 192.10 Gb of clean sequence data were generated through WGRS of resistant parent and the resistant and susceptible bulks for rust and LLS. Sequence analysis of bulks for rust and LLS with reference-guided resistant parent assembly identified 3136 single-nucleotide polymorphisms (SNPs) for rust and 66 SNPs for LLS with the read depth of ≥7 in the identified genomic region on pseudomolecule A03. Detailed analysis identified 30 nonsynonymous SNPs affecting 25 candidate genes for rust resistance, while 14 intronic and three synonymous SNPs affecting nine candidate genes for LLS resistance. Subsequently, allele-specific diagnostic markers were identified for three SNPs for rust resistance and one SNP for LLS resistance. Genotyping of one RIL population (TAG 24 × GPBD 4) with these four diagnostic markers revealed higher phenotypic variation for these two diseases. These results suggest usefulness of QTL-seq approach in precise and rapid identification of candidate genomic regions and development of diagnostic markers for breeding applications. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  2. Thyroid function in girls with menstrual disturbances in iodine-deficiency region

    Directory of Open Access Journals (Sweden)

    O Konstantinova

    2010-06-01

    Full Text Available The estimate the functional state of the female adolescent thyroid with menstrual cycle disorder, living in the iodine deficiency regions, 130 female adolescents with irregular menstrual cycle were examined. Hypothyroidism incidence (in them was 16.9%. In addition we considered TSH range 2.5–4.0 mU/l (highly normal TSH level the extent of which was 12.3%. High extent of antibody carriage to the thyroid (31.3% in girls with irregular menses, having high blood TSH level. There were no statistical differences between the structure of menstrual dysfunction and menstrual duration depending on thyroid function (p = 0.2383, respectively, as well as the average values of estradiol levels depending on TSH level (p = 0.3213. Thus, the influence of highly normal TSH on menstrual function development in female adolescents.

  3. Validating the UNICEF/Washington Group Child Functioning Module for Fijian schools to identify seeing, hearing and walking difficulties.

    Science.gov (United States)

    Sprunt, Beth; Hoq, Monsurul; Sharma, Umesh; Marella, Manjula

    2017-09-20

    This study investigated the seeing, hearing and walking questions of the UNICEF/Washington Group Child Functioning Module and the inter-rater reliability between teachers and parents as proxy respondents. Cross-sectional diagnostic accuracy study, two-gate design with representative sampling, comparing Module responses to reference standard assessments for 472 primary aged students in Fiji. Receiver operating characteristic curves were constructed to determine the area under the curve and optimal cut-off points. Areas under the curves ranged from 0.823 to 0.889 indicating "good" diagnostic accuracy. Inter-rater reliability between parent and teacher responses was "good" to "excellent". The optimal cut-off determined by the Youden Index was "some difficulty" however a wide spread of impairment levels were found in this category with most children either having none or substantial impairments. The diagnostic accuracy of the Module seeing, hearing and walking questions appears acceptable with either parents or teachers as proxy respondents. For education systems, use of the cut-off "some difficulty" with accompanying clinical assessment may be important to capture children who require services and learning supports and avoid potentially misleading categorization. Given the high proportion of the sample from special schools research is required to further test the Module in mainstream schools. Implications for rehabilitation Identification of children who are at risk of disability in Fiji is important to enable planning, monitoring and evaluating access to quality inclusive education. The UNICEF/Washington Group Child Functioning Module appears to be a practical and effective tool that can be used by teachers to identify children at risk of disability. Children identified on the UNICEF/Washington Group Child Functioning Module as having "some difficulty" or higher levels of difficulty in relation to vision, hearing or walking should be referred for further assessment

  4. Disease-associated mutations disrupt functionally important regions of intrinsic protein disorder.

    Directory of Open Access Journals (Sweden)

    Vladimir Vacic

    Full Text Available The effects of disease mutations on protein structure and function have been extensively investigated, and many predictors of the functional impact of single amino acid substitutions are publicly available. The majority of these predictors are based on protein structure and evolutionary conservation, following the assumption that disease mutations predominantly affect folded and conserved protein regions. However, the prevalence of the intrinsically disordered proteins (IDPs and regions (IDRs in the human proteome together with their lack of fixed structure and low sequence conservation raise a question about the impact of disease mutations in IDRs. Here, we investigate annotated missense disease mutations and show that 21.7% of them are located within such intrinsically disordered regions. We further demonstrate that 20% of disease mutations in IDRs cause local disorder-to-order transitions, which represents a 1.7-2.7 fold increase compared to annotated polymorphisms and neutral evolutionary substitutions, respectively. Secondary structure predictions show elevated rates of transition from helices and strands into loops and vice versa in the disease mutations dataset. Disease disorder-to-order mutations also influence predicted molecular recognition features (MoRFs more often than the control mutations. The repertoire of disorder-to-order transition mutations is limited, with five most frequent mutations (R→W, R→C, E→K, R→H, R→Q collectively accounting for 44% of all deleterious disorder-to-order transitions. As a proof of concept, we performed accelerated molecular dynamics simulations on a deleterious disorder-to-order transition mutation of tumor protein p63 and, in agreement with our predictions, observed an increased α-helical propensity of the region harboring the mutation. Our findings highlight the importance of mutations in IDRs and refine the traditional structure-centric view of disease mutations. The results of this study

  5. A detailed study of nucleon structure function in nuclei in the valence quark region

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, N. [INFN-Laboratori, Nazionali di Frascati (Italy)

    1994-04-01

    The so called {open_quotes}EMC effect{close_quotes} discovered during the 1980`s, has caused a big controversy in the community of nuclear and high energy physicists; during the last ten years, five experiments have been performed in different laboratories and several hundreds of papers about the possible interpretation of the modification of the nucleon structure function inside nuclei have been published. However, from the experimental point of view, the main goal of four experiments (EMC, BCDMS, NMC, FNAL) has been to emphasize the region of low x{sub b}, where shadowing effects appear. In the region of valence quarks and nuclear effects (x{sub b} > 0.1 - 0.2) the most reliable data presently available are from the SLAC E139 experiment performed in 1983 with only 80 hours of beam time. New precise data in the valence quark region are necessary to measure separate structure functions F{sub 2}(x{sub b}, Q{sup 2}) and R{sup lt}(x{sub b},Q{sup 2}) = {sigma}{sub l}/{sigma}{sub t}, and to investigate the real A-dependence of the ratio between bound and free-nucleon structure functions which is not completely defined by the SLAC data. Moreover, from the nuclear physics point of view, a measurement on some unexplored nuclei, like {sup 3}He and {sup 48}Ca, would be of great interest. The intermediate scaling region (0.1 < x{sub b} < 0.7) would be accessible at CEBAF if the machine energy will reach 6-8 GeV, as suggested by all the tests performed on the RF cavities. This physics program has been already presented in two letter of intents.

  6. Finite element transport using Wachspress rational basis functions on quadrilaterals in diffusive regions

    International Nuclear Information System (INIS)

    Davidson, G.; Palmer, T.S.

    2005-01-01

    In 1975, Wachspress developed basis functions that can be constructed upon very general zone shapes, including convex polygons and polyhedra, as well as certain zone shapes with curved sides and faces. Additionally, Adams has recently shown that weight functions with certain properties will produce solutions with full-resolution. Wachspress rational functions possess those necessary properties. Here we present methods to construct and integrate Wachspress rational functions on quadrilaterals. We also present an asymptotic analysis of a discontinuous finite element discretization on quadrilaterals, and we present 3 numerical results that confirm the predictions of our analysis. In the first test problem, we showed that Wachspress rational functions could give robust solutions for a strongly heterogeneous problem with both orthogonal and skewed meshes. This strongly heterogenous problem contained thick, diffusive regions, and the discretization provided full-resolution solutions. In the second test problem, we confirmed our asymptotic analysis by demonstrating that the transport solution will converge to the diffusion solution as the problem is made increasingly thick and diffusive. In the third test problem, we demonstrated that bilinear discontinuous based transport and Wachspress rational function based transport converge in the one-mesh limit

  7. Age-related functional changes in gustatory and reward processing regions: An fMRI study.

    Science.gov (United States)

    Jacobson, Aaron; Green, Erin; Murphy, Claire

    2010-11-01

    Changes in appetite in older adults may result in unhealthy weight change and negatively affect overall nutrition. Research examining gustatory processing in young adults has linked changes in patterns of the hemodynamic response of gustatory and motivation related brain regions to the physiological states of hunger and satiety. Whether the same brain regions are involved in taste processing in older adults is unknown. The current study used functional magnetic resonance imaging (fMRI) to examine age-related changes in gustatory processing during hedonic assessment. Caffeine, citric acid, sucrose, and NaCl were administered orally during two event-related fMRI sessions, one during hunger and one after a pre-load. Participants assessed the pleasantness of the solutions in each session. Increased activity of the insula was seen in both age groups during hunger. Activity of secondary and higher order taste processing and reward regions such as the orbitofrontal cortex, amygdala, hippocampus, thalamus, and caudate nucleus was also observed. Hunger and satiety differentially affected the hemodynamic response, resulting in positive global activation during hunger and negative during satiety in both age groups. While in a state of hunger, the frequency and consistency of positive activation in gustatory and reward processing regions was greater in older adults. Additional regions not commonly associated with taste processing were also activated in older adults. Investigating the neurological response of older adults to taste stimuli under conditions of hunger and satiety may aid in understanding appetite, health, and functional changes in this population. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Effect of myocardial viability in the infarct area on regional left ventricular function

    International Nuclear Information System (INIS)

    Ishii, Toshihiko; Watanabe, Takeshi; Usui, Mikio; Nagai, Yoshikazu

    1990-01-01

    This study explored the relationship between global left ventricular ejection fraction (LVEF), regional LVEF of infarct myocardium, and the viability of the myocardium due to the development of collaterals in the infarct area. Each was evaluated by exercise thallium-201 myocardial SPECT, multigated blood pool scintigraphy and coronary angiography. A total of 68 patients with old anteroseptal myocardial infarction and 23 normal persons were studied. The patients were found to have septal defect on exercise thallium images. According to the appearance of redistribution (RD) on delayed images, the patients were classified as having positive RD (n=42, 62%) or negative RD (n=26, 38%). The global LVEF was compared with regional LVEF of the basal, middle and apical areas within septum, as calculated by multigated blood pool scintigraphy. There was no significant difference in global LVEF between the groups of positive and negative RD patients. However, regional LVEF of the basal and middle areas was significantly larger in the group of positive RD than the group of negative RD. Collaterals were significantly observed in the group of positive RD, as compared with the group of negative RD (53% vs 25%). It was more frequent in cases of higher degree of stenosis. In the group of negative RD, none of the patients had collaterals when coronary stenosis was 90% or less. Redistribution may reflect myocardial viability. Myocardial viability within the infarct area had favorable influences on the regional left ventricular function. Therefore, not only global but also regional left ventricular function is necessary for better understanding of pathophysiology of myocardial infarction.(N.K.)

  9. The effects of aerobic exercise on the structure and function of DMN-related brain regions: a systematic review.

    Science.gov (United States)

    Li, Mo-Yi; Huang, Mao-Mao; Li, Shu-Zhen; Tao, Jing; Zheng, Guo-Hua; Chen, Li-Dian

    2017-07-01

    Physical activity may play a role in both the prevention and slowing of brain volume loss and may be beneficial in terms of improving the functional connectivity of brain regions. But much less is known about the potential benefit of aerobic exercise for the structure and function of the default mode network (DMN) brain regions. This systematic review examines the effects of aerobic exercise on the structure and function of DMN brain regions in human adulthood. Seven electronic databases were searched for prospective controlled studies published up to April 2015. The quality of the selected studies was evaluated with the Cochrane Collaboration's tool for assessing the risk of bias. RevMan 5.3 software was applied for data analysis. Finally, 14 studies with 631 participants were identified. Meta-analysis revealed that aerobic exercise could significantly increase right hippocampal volume (SMD = 0.26, 95% CI 0.01-0.51, p = 0.04, I 2 = 7%, 4 studies), and trends of similar effects were observed in the total (SMD = 0.12, 95% CI -0.17 to 0.41, p = 0.43, I 2 = 0%, 5 studies), left (SMD = 0.12, 95% CI -0.13 to 0.37, p = 0.33, I 2 = 14%, 4 studies), left anterior (SMD = 0.12, 95% CI -0.16 to 0.40, p = 0.41, I 2 = 74%, 2 studies) and right anterior (SMD = 0.10, 95% CI -0.17 to 0.38, p = 0.46, I 2 = 76%, 4 studies) hippocampal volumes compared to the no-exercise interventions. A few studies reported that relative to no-exercise interventions, aerobic exercise could significantly decrease the atrophy of the medial temporal lobe, slow the anterior cingulate cortex (ACC) volume loss, increase functional connectivity within the hippocampus and improve signal activation in the cingulate gyrus and ACC. The current review suggests that aerobic exercise may have positive effects on the right hippocampus and potentially beneficial effects on the overall and other parts of the hippocampus, the cingulate cortex and the medial temporal areas of the DMN. Moreover, aerobic exercise may

  10. The hyporheic zone and its functions: revision and research status in Neotropical regions

    Directory of Open Access Journals (Sweden)

    R Mugnai

    Full Text Available AbstractThe hyporheic zone (HZ, as the connecting ecotone between surface- and groundwater, is functionally part of both fluvial and groundwater ecosystems. Its hydrological, chemical, biological and metabolic features are specific of this zone, not belonging truly neither to surface- nor to groundwater. Exchanges of water, nutrients, and organic matter occur in response to variations in discharge and bed topography and porosity. Dynamic gradients exist at all scales and vary temporally. Across all scales, the functional significance of the HZ relates to its activity and connection with the surface stream. The HZ is a relatively rich environment and almost all invertebrate groups have colonized this habitat. This fauna, so-called hyporheos, is composed of species typical from interstitial environment, and also of benthic epigean and phreatic species. The hyporheic microbiocenose consists in bacteria, archaea, protozoa and fungi. The HZ provides several ecosystem services, playing a pivotal role in mediating exchange processes, including both matter and energy, between surface and subterranean ecosystems, functioning as regulator of water flow, benthic invertebrates refuge and place of storage, source and transformation of organic matter. The hyporheic zone is one of the most threatened aquatic environments, being strongly influenced by human activities, and the least protected by legislation worldwide. Its maintenance and conservation is compelling in order to preserve the ecological interconnectivity among the three spatial dimensions of the aquatic environment. Although several researchers addressed the importance of the hyporheic zone early, and most contemporary stream ecosystem models explicitly include it, very little is known about the HZ of Neotropical regions. From a biological standpoint, hyporheos fauna in Neotropical regions are still largely underestimated. This review focuses on a brief presentation of the hyporheic zone and its

  11. The hyporheic zone and its functions: revision and research status in Neotropical regions.

    Science.gov (United States)

    Mugnai, R; Messana, G; Di Lorenzo, T

    2015-08-01

    The hyporheic zone (HZ), as the connecting ecotone between surface- and groundwater, is functionally part of both fluvial and groundwater ecosystems. Its hydrological, chemical, biological and metabolic features are specific of this zone, not belonging truly neither to surface- nor to groundwater. Exchanges of water, nutrients, and organic matter occur in response to variations in discharge and bed topography and porosity. Dynamic gradients exist at all scales and vary temporally. Across all scales, the functional significance of the HZ relates to its activity and connection with the surface stream. The HZ is a relatively rich environment and almost all invertebrate groups have colonized this habitat. This fauna, so-called hyporheos, is composed of species typical from interstitial environment, and also of benthic epigean and phreatic species. The hyporheic microbiocenose consists in bacteria, archaea, protozoa and fungi. The HZ provides several ecosystem services, playing a pivotal role in mediating exchange processes, including both matter and energy, between surface and subterranean ecosystems, functioning as regulator of water flow, benthic invertebrates refuge and place of storage, source and transformation of organic matter. The hyporheic zone is one of the most threatened aquatic environments, being strongly influenced by human activities, and the least protected by legislation worldwide. Its maintenance and conservation is compelling in order to preserve the ecological interconnectivity among the three spatial dimensions of the aquatic environment. Although several researchers addressed the importance of the hyporheic zone early, and most contemporary stream ecosystem models explicitly include it, very little is known about the HZ of Neotropical regions. From a biological standpoint, hyporheos fauna in Neotropical regions are still largely underestimated. This review focuses on a brief presentation of the hyporheic zone and its functions and significance as

  12. Studing Regional Wave Source Time Functions Using A Massive Automated EGF Deconvolution Procedure

    Science.gov (United States)

    Xie, J. "; Schaff, D. P.

    2010-12-01

    Reliably estimated source time functions (STF) from high-frequency regional waveforms, such as Lg, Pn and Pg, provide important input for seismic source studies, explosion detection, and minimization of parameter trade-off in attenuation studies. The empirical Green’s function (EGF) method can be used for estimating STF, but it requires a strict recording condition. Waveforms from pairs of events that are similar in focal mechanism, but different in magnitude must be on-scale recorded on the same stations for the method to work. Searching for such waveforms can be very time consuming, particularly for regional waves that contain complex path effects and have reduced S/N ratios due to attenuation. We have developed a massive, automated procedure to conduct inter-event waveform deconvolution calculations from many candidate event pairs. The procedure automatically evaluates the “spikiness” of the deconvolutions by calculating their “sdc”, which is defined as the peak divided by the background value. The background value is calculated as the mean absolute value of the deconvolution, excluding 10 s around the source time function. When the sdc values are about 10 or higher, the deconvolutions are found to be sufficiently spiky (pulse-like), indicating similar path Green’s functions and good estimates of the STF. We have applied this automated procedure to Lg waves and full regional wavetrains from 989 M ≥ 5 events in and around China, calculating about a million deconvolutions. Of these we found about 2700 deconvolutions with sdc greater than 9, which, if having a sufficiently broad frequency band, can be used to estimate the STF of the larger events. We are currently refining our procedure, as well as the estimated STFs. We will infer the source scaling using the STFs. We will also explore the possibility that the deconvolution procedure could complement cross-correlation in a real time event-screening process.

  13. Functional dissection of Streptococcus pyogenes M5 protein: the hypervariable region is essential for virulence.

    Directory of Open Access Journals (Sweden)

    Johan Waldemarsson

    Full Text Available The surface-localized M protein of Streptococcus pyogenes is a major virulence factor that inhibits phagocytosis, as determined ex vivo. Because little is known about the role of M protein in vivo we analyzed the contribution of different M protein regions to virulence, using the fibrinogen (Fg-binding M5 protein and a mouse model of acute invasive infection. This model was suitable, because M5 is required for mouse virulence and binds mouse and human Fg equally well, as shown here. Mixed infection experiments with wild type bacteria demonstrated that mutants lacking the N-terminal hypervariable region (HVR or the Fg-binding B-repeat region were strongly attenuated, while a mutant lacking the conserved C-repeats was only slightly attenuated. Because the HVR of M5 is not required for phagocytosis resistance, our data imply that this HVR plays a major but unknown role during acute infection. The B-repeat region is required for phagocytosis resistance and specifically binds Fg, suggesting that it promotes virulence by binding Fg. However, B-repeat mutants were attenuated even in Fg-deficient mice, implying that the B-repeats may have a second function, in addition to Fg-binding. These data demonstrate that two distinct M5 regions, including the HVR, are essential to virulence during the early stages of an infection. In particular, our data provide the first in vivo evidence that the HVR of an M protein plays a major role in virulence, focusing interest on the molecular role of this region.

  14. Identifying parameter regions for multistationarity

    DEFF Research Database (Denmark)

    Conradi, Carsten; Feliu, Elisenda; Mincheva, Maya

    2017-01-01

    is the avoidance of numerical analysis and parameter sampling. The procedure consists of a number of steps. Each of these steps might be addressed algorithmically using various computer programs and available software, or manually. We demonstrate our procedure on several models of gene transcription and cell...

  15. Determinants of life expectancy in eastern mediterranean region: a health production function.

    Science.gov (United States)

    Bayati, Mohsen; Akbarian, Reza; Kavosi, Zahra

    2013-06-01

    Determinants of health or health production function in health economics literature constitute noticeable issues in health promotion. This study aimed at estimating a health production function for East Mediterranean Region (EMR) based on the Grossman theoretical model. This ecological study was performed using the econometric methods. The panel data model was used in order to determine the relationship between life expectancy and socioeconomic factors. The data for 21 EMR countries between 1995 and 2007 were used. Fixed-effect-model was employed to estimate the parameters based on Hausman test. In estimating the health production function, factors such as income per capita (β=0.05, Pdeterminants of health status, proxied by life expectancy at birth. A notable result was the elasticity of life expectancy with respect to the employment rate and its significance level was different between males (β=0.13, P0.001). In order to improve the health status in EMR countries, health policymakers should focus on the factors which lie outside the healthcare system. These factors are mainly associated with economic growth and development level. Thus, the economic stabilisation policies with the aim of increasing the productivity, economic growth, and reducing unemployment play significant roles in the health status of the people of the region.

  16. The Ironbridge Gorge Heritage Site and its local and regional functions

    Directory of Open Access Journals (Sweden)

    Cudny Waldemar

    2017-06-01

    Full Text Available The article is devoted to the issue of heritage and its functions. Based on the existing literature, the author presents the definition of heritage, the classification of heritage resources, and its most important impacts. The aim of the article was to show the functions that may be performed by a heritage site, locally and regionally. The example used by the author is the Ironbridge Gorge Heritage Site in the United Kingdom. Most heritage functions described by other authors are confirmed in this case study. The cultural heritage of the Ironbridge Gorge creates an opportunity to undertake various local and regional activities, having first of all an educational influence on the inhabitants, school youth and tourists. We must not ignore the economicinfluences, such as financing the activity of the Ironbridge Trust (the institution administering the site, generating income for local firms providing service to tourists, or for construction companies. This income helps to preserve and conserve the tangible heritage of the Ironbridge Gorge, as well as to generate jobs in heritage management, conservation and heritage tourism. Other effects of the Ironbridge Gorge Site include a socio-cultural impact or that related to sustainable development.

  17. Crystal Structure Analysis and the Identification of Distinctive Functional Regions of the Protein Elicitor Mohrip2.

    Science.gov (United States)

    Liu, Mengjie; Duan, Liangwei; Wang, Meifang; Zeng, Hongmei; Liu, Xinqi; Qiu, Dewen

    2016-01-01

    The protein elicitor MoHrip2, which was extracted from Magnaporthe oryzae as an exocrine protein, triggers the tobacco immune system and enhances blast resistance in rice. However, the detailed mechanisms by which MoHrip2 acts as an elicitor remain unclear. Here, we investigated the structure of MoHrip2 to elucidate its functions based on molecular structure. The three-dimensional structure of MoHrip2 was obtained. Overall, the crystal structure formed a β-barrel structure and showed high similarity to the pathogenesis-related (PR) thaumatin superfamily protein thaumatin-like xylanase inhibitor (TL-XI). To investigate the functional regions responsible for MoHrip2 elicitor activities, the full length and eight truncated proteins were expressed in Escherichia coli and were evaluated for elicitor activity in tobacco. Biological function analysis showed that MoHrip2 triggered the defense system against Botrytis cinerea in tobacco. Moreover, only MoHrip2M14 and other fragments containing the 14 amino acids residues in the middle region of the protein showed the elicitor activity of inducing a hypersensitive response and resistance related pathways, which were similar to that of full-length MoHrip2. These results revealed that the central 14 amino acid residues were essential for anti-pathogenic activity.

  18. Transferability of species distribution models: a functional habitat approach for two regionally threatened butterflies.

    Science.gov (United States)

    Vanreusel, Wouter; Maes, Dirk; Van Dyck, Hans

    2007-02-01

    Numerous models for predicting species distribution have been developed for conservation purposes. Most of them make use of environmental data (e.g., climate, topography, land use) at a coarse grid resolution (often kilometres). Such approaches are useful for conservation policy issues including reserve-network selection. The efficiency of predictive models for species distribution is usually tested on the area for which they were developed. Although highly interesting from the point of view of conservation efficiency, transferability of such models to independent areas is still under debate. We tested the transferability of habitat-based predictive distribution models for two regionally threatened butterflies, the green hairstreak (Callophrys rubi) and the grayling (Hipparchia semele), within and among three nature reserves in northeastern Belgium. We built predictive models based on spatially detailed maps of area-wide distribution and density of ecological resources. We used resources directly related to ecological functions (host plants, nectar sources, shelter, microclimate) rather than environmental surrogate variables. We obtained models that performed well with few resource variables. All models were transferable--although to different degrees--among the independent areas within the same broad geographical region. We argue that habitat models based on essential functional resources could transfer better in space than models that use indirect environmental variables. Because functional variables can easily be interpreted and even be directly affected by terrain managers, these models can be useful tools to guide species-adapted reserve management.

  19. Crystal Structure Analysis and the Identification of Distinctive Functional Regions of the Protein Elicitor Mohrip2

    Directory of Open Access Journals (Sweden)

    Mengjie Liu

    2016-07-01

    Full Text Available The protein elicitor MoHrip2, which was extracted from Magnaporthe oryzae as an exocrine protein, triggers the tobacco immune system and enhances blast resistance in rice. However, the detailed mechanisms by which MoHrip2 acts as an elicitor remain unclear. Here, we investigated the structure of MoHrip2 to elucidate its functions based on molecular structure. The 3-dimensional structure of MoHrip2 was obtained. Overall, the crystal structure formed a β-barrel structure and showed high similarity to the pathogenesis-related (PR thaumatin superfamily protein thaumatin-like xylanase inhibitor (TL-XI. To investigate the functional regions responsible for MoHrip2 elicitor activities, the full length and 8 truncated proteins were expressed in Escherichia coli and were evaluated for elicitor activity in tobacco. Biological function analysis showed that MoHrip2 triggered the defense system against Botrytis cinerea in tobacco. Moreover, only MoHrip2M14 and other fragments containing the 14 amino acids residues in the middle region of the protein showed the elicitor activity of inducing a hypersensitive response and resistance related pathways, which were similar to that of full-length MoHrip2. These results revealed that the central 14 amino acid residues were essential for anti-pathogenic activity.

  20. A Regional Guidebook for Conducting Functional Assessments of Forested Wetlands in the Arkansas Valley Region of Arkansas

    National Research Council Canada - National Science Library

    Klimas, Charles V; Murray, Elizabeth O; Langston, Henry; Pagan, Jody; Witsell, Theo; Foti, Thomas

    2008-01-01

    .... The Hydrogeomorphic Approach is a collection of concepts and methods for developing functional indices and subsequently using them to assess the capacity of a wetland to perform functions relative...

  1. A Regional Guidebook for Conducting Functional Assessments of Forested Wetlands and Riparian Areas in the Ozark Mountains Region of Arkansas

    National Research Council Canada - National Science Library

    Klimas, Charles V; Murray, Elizabeth O; Langston, Henry; Pagan, Jody; Witsell, Theo; Foti, Thomas

    2008-01-01

    .... The Hydrogeomorphic Approach is a collection of concepts and methods for developing functional indices and subsequently using them to assess the capacity of a wetland to perform functions relative...

  2. Functional modulation of cardiac form through regionally confined cell shape changes.

    Directory of Open Access Journals (Sweden)

    Heidi J Auman

    2007-03-01

    Full Text Available Developing organs acquire a specific three-dimensional form that ensures their normal function. Cardiac function, for example, depends upon properly shaped chambers that emerge from a primitive heart tube. The cellular mechanisms that control chamber shape are not yet understood. Here, we demonstrate that chamber morphology develops via changes in cell morphology, and we determine key regulatory influences on this process. Focusing on the development of the ventricular chamber in zebrafish, we show that cardiomyocyte cell shape changes underlie the formation of characteristic chamber curvatures. In particular, cardiomyocyte elongation occurs within a confined area that forms the ventricular outer curvature. Because cardiac contractility and blood flow begin before chambers emerge, cardiac function has the potential to influence chamber curvature formation. Employing zebrafish mutants with functional deficiencies, we find that blood flow and contractility independently regulate cell shape changes in the emerging ventricle. Reduction of circulation limits the extent of cardiomyocyte elongation; in contrast, disruption of sarcomere formation releases limitations on cardiomyocyte dimensions. Thus, the acquisition of normal cardiomyocyte morphology requires a balance between extrinsic and intrinsic physical forces. Together, these data establish regionally confined cell shape change as a cellular mechanism for chamber emergence and as a link in the relationship between form and function during organ morphogenesis.

  3. Molecular Characterization and Functional Analysis of PR-1-Like Proteins Identified from the Wheat Head Blight Fungus Fusarium graminearum.

    Science.gov (United States)

    Lu, Shunwen; Edwards, Michael C

    2018-04-01

    The group 1 pathogenesis-related (PR-1) proteins originally identified from plants and their homologs are also found in other eukaryotic kingdoms. Studies on nonplant PR-1-like (PR-1L) proteins have been pursued widely in humans and animals but rarely in filamentous ascomycetes. Here, we report the characterization of four PR-1L proteins identified from the ascomycete fungus Fusarium graminearum, the primary cause of Fusarium head blight of wheat and barley (designated FgPR-1L). Molecular cloning revealed that the four FgPR-1L proteins are all encoded by small open reading frames (612 to 909 bp) that are often interrupted by introns, in contrast to plant PR-1 genes that lack introns. Sequence analysis indicated that all FgPR-1L proteins contain the PR-1-specific three-dimensional structure, and one of them features a C-terminal transmembrane (TM) domain that has not been reported for any stand-alone PR-1 proteins. Transcriptional analysis revealed that the four FgPR-1L genes are expressed in axenic cultures and in planta with different spatial or temporal expression patterns. Phylogenetic analysis indicated that fungal PR-1L proteins fall into three major groups, one of which harbors FgPR-1L-2-related TM-containing proteins from both phytopathogenic and human-pathogenic ascomycetes. Low-temperature sodium dodecyl sulfate polyacrylamide gel electrophoresis and proteolytic assays indicated that the recombinant FgPR-1L-4 protein exists as a monomer and is resistant to subtilisin of the serine protease family. Functional analysis confirmed that deletion of the FgPR-1L-4 gene from the fungal genome results in significantly reduced virulence on susceptible wheat. This study provides the first example that the F. graminearum-wheat interaction involves a pathogen-derived PR-1L protein that affects fungal virulence on the host.

  4. A functional glycoproteomics approach identifies CD13 as a novel E-selectin ligand in breast cancer.

    Science.gov (United States)

    Carrascal, M A; Silva, M; Ferreira, J A; Azevedo, R; Ferreira, D; Silva, A M N; Ligeiro, D; Santos, L L; Sackstein, R; Videira, P A

    2018-05-17

    The glycan moieties sialyl-Lewis-X and/or -A (sLe X/A ) are the primary ligands for E-selectin, regulating subsequent tumor cell extravasation into distant organs. However, the nature of the glycoprotein scaffolds displaying these glycans in breast cancer remains unclear and constitutes the focus of the present investigation. We isolated glycoproteins that bind E-selectin from the CF1_T breast cancer cell line, derived from a patient with ductal carcinoma. Proteins were identified using bottom-up proteomics approach by nanoLC-orbitrap LTQ-MS/MS. Data were curated using bioinformatics tools to highlight clinically relevant glycoproteins, which were validated by flow cytometry, Western blot, immunohistochemistry and in-situ proximity ligation assays in clinical samples. We observed that the CF1_T cell line expressed sLe X , but not sLe A and the E-selectin reactivity was mainly on N-glycans. MS and bioinformatics analysis of the targeted glycoproteins, when narrowed down to the most clinically relevant species in breast cancer, identified CD44 glycoprotein (HCELL) and CD13 as key E-selectin ligands. Additionally, the co-expression of sLe X -CD44 and sLe X -CD13 was confirmed in clinical breast cancer tissue samples. Both CD44 and CD13 glycoforms display sLe X in breast cancer and bind E-selectin, suggesting a key role in metastasis development. Such observations provide a novel molecular rationale for developing targeted therapeutics. While HCELL expression in breast cancer has been previously reported, this is the first study indicating that CD13 functions as an E-selectin ligand in breast cancer. This observation supports previous associations of CD13 with metastasis and draws attention to this glycoprotein as an anti-cancer target. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Genetic association study identifies a functional CNV in the WWOX gene contributes to the risk of intracranial aneurysms.

    Science.gov (United States)

    Fan, Jin; Sun, Wen; Lin, Min; Yu, Ke; Wang, Jian; Duan, Dan; Zheng, Bo; Yang, Zhenghui; Wang, Qingsong

    2016-03-29

    Intracranial aneurysms (IAs) accounts for 85% of hemorrhagic stroke. Genetic factors have been known to play an important role in the development of IAs. A functional CNV (CNV-67048) of human WW domain-containing oxidoreductase (WWOX), which has been identified as a tumor suppressor gene in multiple cancers, was identified to be associated with gliomas risk previously. Here, we hypothesized that the CNV-67048 could also affect susceptibility of IAs. Based on a two-stage, case- control study with a total of 976 patients of IAs and 1,200 matched healthy controls, we found the effect size for per copy deletion was 1.35 (95% CI = 1.16-1.57; Ptrend = 1.18 × 10-4). Compared with the individuals having no deletion, significantly higher risk of IAs was detected for both subjects carrying 1 copy deletion (OR = 1.24, 95% CI = 1.02-1.52) and subjects carrying 2 copy deletion (OR = 1.77, 95% CI = 1.24-2.53). Real-time PCR was used to confirm the abnormal expression of WWOX in tissues of IA patients and influence of genotypes of CNV-67048. The expression level of WWOX in IA tissues was significantly lower than that in corresponding normal tissues (P = 0.004), and the deletion genotypes of CNV-67048 have lower WWOX mRNA levels in both tumor tissues and border tissues (P 48 in WWOX predispose their carriers to IAs, which might be a genetic biomarker to predict risk of IAs in Chinese.

  6. Virtual screening approach to identifying influenza virus neuraminidase inhibitors using molecular docking combined with machine-learning-based scoring function.

    Science.gov (United States)

    Zhang, Li; Ai, Hai-Xin; Li, Shi-Meng; Qi, Meng-Yuan; Zhao, Jian; Zhao, Qi; Liu, Hong-Sheng

    2017-10-10

    In recent years, an epidemic of the highly pathogenic avian influenza H7N9 virus has persisted in China, with a high mortality rate. To develop novel anti-influenza therapies, we have constructed a machine-learning-based scoring function (RF-NA-Score) for the effective virtual screening of lead compounds targeting the viral neuraminidase (NA) protein. RF-NA-Score is more accurate than RF-Score, with a root-mean-square error of 1.46, Pearson's correlation coefficient of 0.707, and Spearman's rank correlation coefficient of 0.707 in a 5-fold cross-validation study. The performance of RF-NA-Score in a docking-based virtual screening of NA inhibitors was evaluated with a dataset containing 281 NA inhibitors and 322 noninhibitors. Compared with other docking-rescoring virtual screening strategies, rescoring with RF-NA-Score significantly improved the efficiency of virtual screening, and a strategy that averaged the scores given by RF-NA-Score, based on the binding conformations predicted with AutoDock, AutoDock Vina, and LeDock, was shown to be the best strategy. This strategy was then applied to the virtual screening of NA inhibitors in the SPECS database. The 100 selected compounds were tested in an in vitro H7N9 NA inhibition assay, and two compounds with novel scaffolds showed moderate inhibitory activities. These results indicate that RF-NA-Score improves the efficiency of virtual screening for NA inhibitors, and can be used successfully to identify new NA inhibitor scaffolds. Scoring functions specific for other drug targets could also be established with the same method.

  7. CD45RC isoform expression identifies functionally distinct T cell subsets differentially distributed between healthy individuals and AAV patients.

    Directory of Open Access Journals (Sweden)

    Laurence Ordonez

    Full Text Available In animal models of anti-neutrophil cytoplasmic antibody (ANCA-associated vasculitis (AAV, the proportion of CD45RC T cell subsets is important for disease susceptibility. Their human counterparts are, however, functionally ill defined. In this report, we studied their distribution in healthy controls (HC, AAV patients and in Systemic lupus erythematous (SLE patients as disease controls. We showed that CD45RC expression level on human CD4 and CD8 T cells identifies subsets that are highly variable among individuals. Interestingly, AAV patients exhibit an increased proportion of CD45RC(low CD4 T cells as compared to HC and SLE patients. This increase is stable over time and independent of AAV subtype, ANCA specificity, disease duration, or number of relapses. We also analyzed the cytokine profile of purified CD4 and CD8 CD45RC T cell subsets from HC, after stimulation with anti-CD3 and anti-CD28 mAbs. The CD45RC subsets exhibit different cytokine profiles. Type-1 cytokines (IL-2, IFN-gamma and TNF-alpha were produced by all CD45RC T cell subsets, while the production of IL-17, type-2 (IL-4, IL-5 and regulatory (IL-10 cytokines was restricted to the CD45RC(low subset. In conclusion, we have shown that CD45RC expression divides human T cells in functionally distinct subsets that are imbalanced in AAV. Since this imbalance is stable over time and independent of several disease parameters, we hypothesize that this is a pre-existing immune abnormality involved in the etiology of AAV.